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COVID vaccination does not appear to worsen symptoms of Parkinson’s disease
Nonmotor symptoms seemed to improve after SARS-CoV-2 vaccination, although the investigators could not verify a causal relationship.
Vaccination programs should continue for patients with Parkinson’s disease, they said, reporting their clinical results at the International Congress of Parkinson’s Disease and Movement Disorders.
The International Parkinson and Movement Disorder Society has recommended vaccining patients with Parkinson’s disease. “All approved mRNA-based and viral vector vaccines are not expected to interact with Parkinson’s disease, but patients [still] report concern with regard to the benefits, risks, and safeness in Parkinson’s disease,” Mayela Rodríguez-Violante, MD, MSc, and colleagues wrote in an abstract of their findings.
Social isolation may be contributing to these beliefs and concerns, though this is inconclusive.
Investigators from Mexico City conducted a retrospective study of patients with Parkinson’s disease to see how COVID-19 vaccination affected motor and nonmotor symptoms. They enlisted 60 patients (66.7% were male; aged 65.7 ± 11.35 years) who received either a vector-viral vaccine (Vaxzevria Coronavirus) or an mRNA vaccine (BNT162b2).
A Wilcoxon signed-rank test assessed scale differences before and after vaccination, measuring motor involvement (Unified Parkinson’s Disease Rating Scale), nonmotor involvement (Non-Motor Rating Scale [NMSS]), cognitive impairment (Montreal Cognitive Assessment), and quality of life (8-item Parkinson’s Disease Questionnaire index).
Investigators found no significant difference between scales, although they did notice a marked improvement in non-motor symptoms.
“The main takeaway is that vaccination against COVID-19 does not appear to worsen motor or nonmotor symptoms in persons with Parkinson’s disease. The benefits outweigh the risks,” said Dr. Rodríguez-Violante, the study’s lead author and a movement disorder specialist at the National Institute of Neurology and Neurosurgery, Mexico City.
Next steps are to increase the sample size to see if it’s possible to have a similar number in terms of type of vaccine, said Dr. Rodríguez-Violante. “Also, the data presented refers to primary series doses so booster effects will also be studied.”
Few studies have looked at vaccines and their possible effects on this patient population. However, a 2021 study of 181 patients with Parkinson’s disease reported that 2 (1.1%) had adverse effects after receiving the BNT162b2 mRNA vaccine. One of the patients, a 61-year-old woman with a decade-long history of Parkinson’s disease, developed severe, continuous, generalized dyskinesia 6 hours after a first dose of vaccine. The second patient was 79 years old and had Parkinson’s disease for 5 years. She developed fever, confusion, delusions, and continuous severe dyskinesia for 3 days following her vaccination.
“This highlights that there is a variability in the response triggered by the vaccine that might likely depend on individual immunological profiles … clinicians should be aware of this possibility and monitor their patients after they receive their vaccination,” Roberto Erro, MD, PhD and colleagues wrote in the Movement Disorders journal.
Nonmotor symptoms seemed to improve after SARS-CoV-2 vaccination, although the investigators could not verify a causal relationship.
Vaccination programs should continue for patients with Parkinson’s disease, they said, reporting their clinical results at the International Congress of Parkinson’s Disease and Movement Disorders.
The International Parkinson and Movement Disorder Society has recommended vaccining patients with Parkinson’s disease. “All approved mRNA-based and viral vector vaccines are not expected to interact with Parkinson’s disease, but patients [still] report concern with regard to the benefits, risks, and safeness in Parkinson’s disease,” Mayela Rodríguez-Violante, MD, MSc, and colleagues wrote in an abstract of their findings.
Social isolation may be contributing to these beliefs and concerns, though this is inconclusive.
Investigators from Mexico City conducted a retrospective study of patients with Parkinson’s disease to see how COVID-19 vaccination affected motor and nonmotor symptoms. They enlisted 60 patients (66.7% were male; aged 65.7 ± 11.35 years) who received either a vector-viral vaccine (Vaxzevria Coronavirus) or an mRNA vaccine (BNT162b2).
A Wilcoxon signed-rank test assessed scale differences before and after vaccination, measuring motor involvement (Unified Parkinson’s Disease Rating Scale), nonmotor involvement (Non-Motor Rating Scale [NMSS]), cognitive impairment (Montreal Cognitive Assessment), and quality of life (8-item Parkinson’s Disease Questionnaire index).
Investigators found no significant difference between scales, although they did notice a marked improvement in non-motor symptoms.
“The main takeaway is that vaccination against COVID-19 does not appear to worsen motor or nonmotor symptoms in persons with Parkinson’s disease. The benefits outweigh the risks,” said Dr. Rodríguez-Violante, the study’s lead author and a movement disorder specialist at the National Institute of Neurology and Neurosurgery, Mexico City.
Next steps are to increase the sample size to see if it’s possible to have a similar number in terms of type of vaccine, said Dr. Rodríguez-Violante. “Also, the data presented refers to primary series doses so booster effects will also be studied.”
Few studies have looked at vaccines and their possible effects on this patient population. However, a 2021 study of 181 patients with Parkinson’s disease reported that 2 (1.1%) had adverse effects after receiving the BNT162b2 mRNA vaccine. One of the patients, a 61-year-old woman with a decade-long history of Parkinson’s disease, developed severe, continuous, generalized dyskinesia 6 hours after a first dose of vaccine. The second patient was 79 years old and had Parkinson’s disease for 5 years. She developed fever, confusion, delusions, and continuous severe dyskinesia for 3 days following her vaccination.
“This highlights that there is a variability in the response triggered by the vaccine that might likely depend on individual immunological profiles … clinicians should be aware of this possibility and monitor their patients after they receive their vaccination,” Roberto Erro, MD, PhD and colleagues wrote in the Movement Disorders journal.
Nonmotor symptoms seemed to improve after SARS-CoV-2 vaccination, although the investigators could not verify a causal relationship.
Vaccination programs should continue for patients with Parkinson’s disease, they said, reporting their clinical results at the International Congress of Parkinson’s Disease and Movement Disorders.
The International Parkinson and Movement Disorder Society has recommended vaccining patients with Parkinson’s disease. “All approved mRNA-based and viral vector vaccines are not expected to interact with Parkinson’s disease, but patients [still] report concern with regard to the benefits, risks, and safeness in Parkinson’s disease,” Mayela Rodríguez-Violante, MD, MSc, and colleagues wrote in an abstract of their findings.
Social isolation may be contributing to these beliefs and concerns, though this is inconclusive.
Investigators from Mexico City conducted a retrospective study of patients with Parkinson’s disease to see how COVID-19 vaccination affected motor and nonmotor symptoms. They enlisted 60 patients (66.7% were male; aged 65.7 ± 11.35 years) who received either a vector-viral vaccine (Vaxzevria Coronavirus) or an mRNA vaccine (BNT162b2).
A Wilcoxon signed-rank test assessed scale differences before and after vaccination, measuring motor involvement (Unified Parkinson’s Disease Rating Scale), nonmotor involvement (Non-Motor Rating Scale [NMSS]), cognitive impairment (Montreal Cognitive Assessment), and quality of life (8-item Parkinson’s Disease Questionnaire index).
Investigators found no significant difference between scales, although they did notice a marked improvement in non-motor symptoms.
“The main takeaway is that vaccination against COVID-19 does not appear to worsen motor or nonmotor symptoms in persons with Parkinson’s disease. The benefits outweigh the risks,” said Dr. Rodríguez-Violante, the study’s lead author and a movement disorder specialist at the National Institute of Neurology and Neurosurgery, Mexico City.
Next steps are to increase the sample size to see if it’s possible to have a similar number in terms of type of vaccine, said Dr. Rodríguez-Violante. “Also, the data presented refers to primary series doses so booster effects will also be studied.”
Few studies have looked at vaccines and their possible effects on this patient population. However, a 2021 study of 181 patients with Parkinson’s disease reported that 2 (1.1%) had adverse effects after receiving the BNT162b2 mRNA vaccine. One of the patients, a 61-year-old woman with a decade-long history of Parkinson’s disease, developed severe, continuous, generalized dyskinesia 6 hours after a first dose of vaccine. The second patient was 79 years old and had Parkinson’s disease for 5 years. She developed fever, confusion, delusions, and continuous severe dyskinesia for 3 days following her vaccination.
“This highlights that there is a variability in the response triggered by the vaccine that might likely depend on individual immunological profiles … clinicians should be aware of this possibility and monitor their patients after they receive their vaccination,” Roberto Erro, MD, PhD and colleagues wrote in the Movement Disorders journal.
FROM MDS 2022
Telehealth effective in managing patients with movement disorders
Researchers presented their findings at the International Congress of Parkinson’s Disease and Movement Disorders.
Serving the underserved
One of the studies – from Kenya, Africa – documented a 2-year experience with telemedicine in a rural patient population.
Kenya suffers from a dearth of neurologists and movement disorder specialists. Most are based in the capital city of Nairobi, “leaving regions with a population of more than 30 million without access to their care,” wrote the study’s investigators. Internists with an interest in neurology usually manage the bulk of these patients.
Telemedicine has helped to bridge gaps between providers in this part of Africa.
Investigators in their study reviewed all cases of movement disorders at Meru Teaching and Referral Hospital and an affiliated clinic, Oregon Health Services, Meru, Kenya, during 2020 and 2021.
They also reviewed WhatsApp messaging, video calls via WhatsApp, patient videos, and phone calls to see how final diagnoses were arrived at using these platforms.
“For instance, a relative would send a video of a patient experiencing a tremor,” explained lead study author Bundi Karau, MD, a consultant physician. “We also shared the diagnostic challenges with experienced neurologists in Kenya and abroad by forwarding WhatsApp and recorded videos of the patients,” he added.
Telemedicine bridged the gap between rural doctors and patients in several ways. It enabled physicians to discuss cases with neurologists in and out of Kenya. “We were able to advise on medical management or further investigations in a more structured pattern and without spending months to make a diagnosis,” said Dr. Karau.
Patients no longer had to travel to Nairobi for care. “Where a direct link could be expensive or out of reach, we bridged this and consequently brought care closer to the patient,” he added.
More than 100 patients were diagnosed with a movement disorder and enrolled in care and follow-up during this 2-year time. Patients averaged about 62 years of age and more than 60% were male. Parkinson’s disease was the most common diagnosed condition (38.9%) followed by drug-induced movement disorders (30.6%), dystonia (11.1%), and functional movement disorders (11.1%).
Investigators found 3 cases of diabetic striatopathy, 8 cases of myoclonus, and 2 cases of Sydenham’s chorea.
Looking ahead, Dr. Karau and colleagues plan to do a cost benefit analysis vis-a-vis traditional physician visits and a trial model for follow-up visits for other neurological diseases.
Wearable devices and apps improve care
Moving from Africa to Greece, investigators in another study assessed the feasibility of using wearable devices to monitor symptoms in patients with Parkinson’s disease.
Such devices may enhance physical exams during virtual visits. Studies have shown that patients can commit to using such devices or mobile apps. What’s lacking is real-world data from everyday device usage, noted lead author George Rigas, PhD, and colleagues.
Fifty-two private physicians instructed a total of 133 patients to wear a device for Parkinson’s disease motor symptom telemonitoring for 1 week per month during waking hours.
Patients used a mobile app to report symptoms, medication, and nutrition adherence and to message their doctor.
The study team noticed that adherence rates stayed above 70% over a 12-month period. Medication and nutrition were among the most popular app features, an encouraging finding given that patients averaged 67 years of age.
“The high adherence percentage is significant, considering the target population and the early stage of telemedicine in Greece,” they concluded. Additional real-world data could help better inform longer-term adherence.
“These studies from all over the world demonstrate that we are only scratching the surface of the telehealth’s potential to improve care and the lives of individuals with Parkinson’s disease,” said Ray Dorsey, MD, a professor of neurology with the Center for Health + Technology at the University of Rochester (N.Y.).
Dr. Dorsey was not involved with the studies but has written and researched extensively on this topic.
Dr. Dorsey is a consultant for and has equity interests in Mediflix and Included Health, two digital health companies.
Researchers presented their findings at the International Congress of Parkinson’s Disease and Movement Disorders.
Serving the underserved
One of the studies – from Kenya, Africa – documented a 2-year experience with telemedicine in a rural patient population.
Kenya suffers from a dearth of neurologists and movement disorder specialists. Most are based in the capital city of Nairobi, “leaving regions with a population of more than 30 million without access to their care,” wrote the study’s investigators. Internists with an interest in neurology usually manage the bulk of these patients.
Telemedicine has helped to bridge gaps between providers in this part of Africa.
Investigators in their study reviewed all cases of movement disorders at Meru Teaching and Referral Hospital and an affiliated clinic, Oregon Health Services, Meru, Kenya, during 2020 and 2021.
They also reviewed WhatsApp messaging, video calls via WhatsApp, patient videos, and phone calls to see how final diagnoses were arrived at using these platforms.
“For instance, a relative would send a video of a patient experiencing a tremor,” explained lead study author Bundi Karau, MD, a consultant physician. “We also shared the diagnostic challenges with experienced neurologists in Kenya and abroad by forwarding WhatsApp and recorded videos of the patients,” he added.
Telemedicine bridged the gap between rural doctors and patients in several ways. It enabled physicians to discuss cases with neurologists in and out of Kenya. “We were able to advise on medical management or further investigations in a more structured pattern and without spending months to make a diagnosis,” said Dr. Karau.
Patients no longer had to travel to Nairobi for care. “Where a direct link could be expensive or out of reach, we bridged this and consequently brought care closer to the patient,” he added.
More than 100 patients were diagnosed with a movement disorder and enrolled in care and follow-up during this 2-year time. Patients averaged about 62 years of age and more than 60% were male. Parkinson’s disease was the most common diagnosed condition (38.9%) followed by drug-induced movement disorders (30.6%), dystonia (11.1%), and functional movement disorders (11.1%).
Investigators found 3 cases of diabetic striatopathy, 8 cases of myoclonus, and 2 cases of Sydenham’s chorea.
Looking ahead, Dr. Karau and colleagues plan to do a cost benefit analysis vis-a-vis traditional physician visits and a trial model for follow-up visits for other neurological diseases.
Wearable devices and apps improve care
Moving from Africa to Greece, investigators in another study assessed the feasibility of using wearable devices to monitor symptoms in patients with Parkinson’s disease.
Such devices may enhance physical exams during virtual visits. Studies have shown that patients can commit to using such devices or mobile apps. What’s lacking is real-world data from everyday device usage, noted lead author George Rigas, PhD, and colleagues.
Fifty-two private physicians instructed a total of 133 patients to wear a device for Parkinson’s disease motor symptom telemonitoring for 1 week per month during waking hours.
Patients used a mobile app to report symptoms, medication, and nutrition adherence and to message their doctor.
The study team noticed that adherence rates stayed above 70% over a 12-month period. Medication and nutrition were among the most popular app features, an encouraging finding given that patients averaged 67 years of age.
“The high adherence percentage is significant, considering the target population and the early stage of telemedicine in Greece,” they concluded. Additional real-world data could help better inform longer-term adherence.
“These studies from all over the world demonstrate that we are only scratching the surface of the telehealth’s potential to improve care and the lives of individuals with Parkinson’s disease,” said Ray Dorsey, MD, a professor of neurology with the Center for Health + Technology at the University of Rochester (N.Y.).
Dr. Dorsey was not involved with the studies but has written and researched extensively on this topic.
Dr. Dorsey is a consultant for and has equity interests in Mediflix and Included Health, two digital health companies.
Researchers presented their findings at the International Congress of Parkinson’s Disease and Movement Disorders.
Serving the underserved
One of the studies – from Kenya, Africa – documented a 2-year experience with telemedicine in a rural patient population.
Kenya suffers from a dearth of neurologists and movement disorder specialists. Most are based in the capital city of Nairobi, “leaving regions with a population of more than 30 million without access to their care,” wrote the study’s investigators. Internists with an interest in neurology usually manage the bulk of these patients.
Telemedicine has helped to bridge gaps between providers in this part of Africa.
Investigators in their study reviewed all cases of movement disorders at Meru Teaching and Referral Hospital and an affiliated clinic, Oregon Health Services, Meru, Kenya, during 2020 and 2021.
They also reviewed WhatsApp messaging, video calls via WhatsApp, patient videos, and phone calls to see how final diagnoses were arrived at using these platforms.
“For instance, a relative would send a video of a patient experiencing a tremor,” explained lead study author Bundi Karau, MD, a consultant physician. “We also shared the diagnostic challenges with experienced neurologists in Kenya and abroad by forwarding WhatsApp and recorded videos of the patients,” he added.
Telemedicine bridged the gap between rural doctors and patients in several ways. It enabled physicians to discuss cases with neurologists in and out of Kenya. “We were able to advise on medical management or further investigations in a more structured pattern and without spending months to make a diagnosis,” said Dr. Karau.
Patients no longer had to travel to Nairobi for care. “Where a direct link could be expensive or out of reach, we bridged this and consequently brought care closer to the patient,” he added.
More than 100 patients were diagnosed with a movement disorder and enrolled in care and follow-up during this 2-year time. Patients averaged about 62 years of age and more than 60% were male. Parkinson’s disease was the most common diagnosed condition (38.9%) followed by drug-induced movement disorders (30.6%), dystonia (11.1%), and functional movement disorders (11.1%).
Investigators found 3 cases of diabetic striatopathy, 8 cases of myoclonus, and 2 cases of Sydenham’s chorea.
Looking ahead, Dr. Karau and colleagues plan to do a cost benefit analysis vis-a-vis traditional physician visits and a trial model for follow-up visits for other neurological diseases.
Wearable devices and apps improve care
Moving from Africa to Greece, investigators in another study assessed the feasibility of using wearable devices to monitor symptoms in patients with Parkinson’s disease.
Such devices may enhance physical exams during virtual visits. Studies have shown that patients can commit to using such devices or mobile apps. What’s lacking is real-world data from everyday device usage, noted lead author George Rigas, PhD, and colleagues.
Fifty-two private physicians instructed a total of 133 patients to wear a device for Parkinson’s disease motor symptom telemonitoring for 1 week per month during waking hours.
Patients used a mobile app to report symptoms, medication, and nutrition adherence and to message their doctor.
The study team noticed that adherence rates stayed above 70% over a 12-month period. Medication and nutrition were among the most popular app features, an encouraging finding given that patients averaged 67 years of age.
“The high adherence percentage is significant, considering the target population and the early stage of telemedicine in Greece,” they concluded. Additional real-world data could help better inform longer-term adherence.
“These studies from all over the world demonstrate that we are only scratching the surface of the telehealth’s potential to improve care and the lives of individuals with Parkinson’s disease,” said Ray Dorsey, MD, a professor of neurology with the Center for Health + Technology at the University of Rochester (N.Y.).
Dr. Dorsey was not involved with the studies but has written and researched extensively on this topic.
Dr. Dorsey is a consultant for and has equity interests in Mediflix and Included Health, two digital health companies.
From MDS 2022
Medical cannabis appears safe for patients with movement disorders
, two Israeli research teams reported.
The practice calls for careful monitoring of patients and additional study, said the researchers, who presented their findings at the International Congress of Parkinson’s Disease and Movement Disorders.
Cannabis for Parkinson’s disease
One retrospective study focused on Parkinson’s disease, evaluating the safety and effects of long-term treatment with medical cannabis, which has become a widely available treatment for controlling symptoms in Parkinson’s disease and other pain disorders. Studies have demonstrated its efficacy in patients with Parkinson’s disease, but long-term safety has never been examined in Parkinson’s disease compared with untreated patients.
Their study included 152 patients with idiopathic Parkinson’s disease (mean age at diagnosis: 55.6 plus or minus 9.5 years) from the Sheba Medical Center Movement Disorders Institute who had been issued a license for medical cannabis. Seventy-six patients treated with cannabis were compared with 76 patients with similar characteristics who were not treated with cannabis.
Investigators collected data on patients who were followed at the institute between 2008 and 2022. Average follow-up period was 3.6 years.
Specifically, they collected data on levodopa equivalent daily dose (LEDD), Hoehn and Yahr scale progression, and patient-reported outcome measures on cognitive impairment, depressive, and psychotic symptoms, at baseline and at follow-up.
The Hoehn and Yahr scale allows for the quantification of different disease stages and LEDD provides a summary of the total daily medication a patient is receiving, explained Tomer Goldberg, BSc, the study’s lead author. Both are widely accepted motor severity and progression measures for Parkinson’s disease. “We wanted to check whether cannabis treatment influences these two motor parameters,” said Mr. Goldberg, who is affiliated with Tel Aviv University and the Movement Disorders Institute at Sheba Medical Center.
The medical cannabis–treated group and the untreated group had no significant differences in the mean annual change in LEDD or Hoehn and Yahr score. At 1, 2, and 3 years of follow-up, the treated group showed no signs of psychotic, depressive, or cognitive deterioration (P = .10-.68). The groups in Kaplan-Meier analyses also exhibited no differences in these nonmotor symptoms over time (P = .27-.93).
The findings suggest that cannabis treatment appears to be safe and has no negative effect on disease progression, said Mr. Goldberg. “It is important to note that we did not investigate all of the potential side effects of this treatment, and that prescribing medical cannabis for patients with Parkinson’s disease should be done with careful monitoring of each patient’s individual response to the treatment,” he added.
Cannabis for Huntington’s disease
Another study, targeting Huntington’s disease, drew similar conclusions. Psychiatric symptoms and cognitive decline are often present in Huntington’s disease patients, who have few treatment options. “An overall improvement in chorea and in neuropsychiatric symptoms was reported following cannabis treatment in several studies both in humans and in murine models,” wrote the study authors.
In this study, a certified Huntington’s disease specialist reviewed the medical records of 150 patients who were being followed in an Huntington’s disease clinic. Study metrics included the Unified Huntington’s Disease Rating Scale and Montreal Cognitive Assessment scores, indications for treatment, and adverse events related to treatment. Among the 150 patients, 19 had received cannabis treatment for indications such as sleep disorders, behavioral anomalies, and chorea. All but one patient reported an improvement in symptoms (94%). No adverse events were recorded, although one patient died from a COVID-19 infection.
Overall, medical cannabis appeared to safely relieve symptoms in patients with Huntington’s disease. A double-blind randomized controlled trial should further examine efficacy of these findings, the study authors recommended.
Mr. Goldberg had no disclosures or conflicts of interest in reporting his research.
, two Israeli research teams reported.
The practice calls for careful monitoring of patients and additional study, said the researchers, who presented their findings at the International Congress of Parkinson’s Disease and Movement Disorders.
Cannabis for Parkinson’s disease
One retrospective study focused on Parkinson’s disease, evaluating the safety and effects of long-term treatment with medical cannabis, which has become a widely available treatment for controlling symptoms in Parkinson’s disease and other pain disorders. Studies have demonstrated its efficacy in patients with Parkinson’s disease, but long-term safety has never been examined in Parkinson’s disease compared with untreated patients.
Their study included 152 patients with idiopathic Parkinson’s disease (mean age at diagnosis: 55.6 plus or minus 9.5 years) from the Sheba Medical Center Movement Disorders Institute who had been issued a license for medical cannabis. Seventy-six patients treated with cannabis were compared with 76 patients with similar characteristics who were not treated with cannabis.
Investigators collected data on patients who were followed at the institute between 2008 and 2022. Average follow-up period was 3.6 years.
Specifically, they collected data on levodopa equivalent daily dose (LEDD), Hoehn and Yahr scale progression, and patient-reported outcome measures on cognitive impairment, depressive, and psychotic symptoms, at baseline and at follow-up.
The Hoehn and Yahr scale allows for the quantification of different disease stages and LEDD provides a summary of the total daily medication a patient is receiving, explained Tomer Goldberg, BSc, the study’s lead author. Both are widely accepted motor severity and progression measures for Parkinson’s disease. “We wanted to check whether cannabis treatment influences these two motor parameters,” said Mr. Goldberg, who is affiliated with Tel Aviv University and the Movement Disorders Institute at Sheba Medical Center.
The medical cannabis–treated group and the untreated group had no significant differences in the mean annual change in LEDD or Hoehn and Yahr score. At 1, 2, and 3 years of follow-up, the treated group showed no signs of psychotic, depressive, or cognitive deterioration (P = .10-.68). The groups in Kaplan-Meier analyses also exhibited no differences in these nonmotor symptoms over time (P = .27-.93).
The findings suggest that cannabis treatment appears to be safe and has no negative effect on disease progression, said Mr. Goldberg. “It is important to note that we did not investigate all of the potential side effects of this treatment, and that prescribing medical cannabis for patients with Parkinson’s disease should be done with careful monitoring of each patient’s individual response to the treatment,” he added.
Cannabis for Huntington’s disease
Another study, targeting Huntington’s disease, drew similar conclusions. Psychiatric symptoms and cognitive decline are often present in Huntington’s disease patients, who have few treatment options. “An overall improvement in chorea and in neuropsychiatric symptoms was reported following cannabis treatment in several studies both in humans and in murine models,” wrote the study authors.
In this study, a certified Huntington’s disease specialist reviewed the medical records of 150 patients who were being followed in an Huntington’s disease clinic. Study metrics included the Unified Huntington’s Disease Rating Scale and Montreal Cognitive Assessment scores, indications for treatment, and adverse events related to treatment. Among the 150 patients, 19 had received cannabis treatment for indications such as sleep disorders, behavioral anomalies, and chorea. All but one patient reported an improvement in symptoms (94%). No adverse events were recorded, although one patient died from a COVID-19 infection.
Overall, medical cannabis appeared to safely relieve symptoms in patients with Huntington’s disease. A double-blind randomized controlled trial should further examine efficacy of these findings, the study authors recommended.
Mr. Goldberg had no disclosures or conflicts of interest in reporting his research.
, two Israeli research teams reported.
The practice calls for careful monitoring of patients and additional study, said the researchers, who presented their findings at the International Congress of Parkinson’s Disease and Movement Disorders.
Cannabis for Parkinson’s disease
One retrospective study focused on Parkinson’s disease, evaluating the safety and effects of long-term treatment with medical cannabis, which has become a widely available treatment for controlling symptoms in Parkinson’s disease and other pain disorders. Studies have demonstrated its efficacy in patients with Parkinson’s disease, but long-term safety has never been examined in Parkinson’s disease compared with untreated patients.
Their study included 152 patients with idiopathic Parkinson’s disease (mean age at diagnosis: 55.6 plus or minus 9.5 years) from the Sheba Medical Center Movement Disorders Institute who had been issued a license for medical cannabis. Seventy-six patients treated with cannabis were compared with 76 patients with similar characteristics who were not treated with cannabis.
Investigators collected data on patients who were followed at the institute between 2008 and 2022. Average follow-up period was 3.6 years.
Specifically, they collected data on levodopa equivalent daily dose (LEDD), Hoehn and Yahr scale progression, and patient-reported outcome measures on cognitive impairment, depressive, and psychotic symptoms, at baseline and at follow-up.
The Hoehn and Yahr scale allows for the quantification of different disease stages and LEDD provides a summary of the total daily medication a patient is receiving, explained Tomer Goldberg, BSc, the study’s lead author. Both are widely accepted motor severity and progression measures for Parkinson’s disease. “We wanted to check whether cannabis treatment influences these two motor parameters,” said Mr. Goldberg, who is affiliated with Tel Aviv University and the Movement Disorders Institute at Sheba Medical Center.
The medical cannabis–treated group and the untreated group had no significant differences in the mean annual change in LEDD or Hoehn and Yahr score. At 1, 2, and 3 years of follow-up, the treated group showed no signs of psychotic, depressive, or cognitive deterioration (P = .10-.68). The groups in Kaplan-Meier analyses also exhibited no differences in these nonmotor symptoms over time (P = .27-.93).
The findings suggest that cannabis treatment appears to be safe and has no negative effect on disease progression, said Mr. Goldberg. “It is important to note that we did not investigate all of the potential side effects of this treatment, and that prescribing medical cannabis for patients with Parkinson’s disease should be done with careful monitoring of each patient’s individual response to the treatment,” he added.
Cannabis for Huntington’s disease
Another study, targeting Huntington’s disease, drew similar conclusions. Psychiatric symptoms and cognitive decline are often present in Huntington’s disease patients, who have few treatment options. “An overall improvement in chorea and in neuropsychiatric symptoms was reported following cannabis treatment in several studies both in humans and in murine models,” wrote the study authors.
In this study, a certified Huntington’s disease specialist reviewed the medical records of 150 patients who were being followed in an Huntington’s disease clinic. Study metrics included the Unified Huntington’s Disease Rating Scale and Montreal Cognitive Assessment scores, indications for treatment, and adverse events related to treatment. Among the 150 patients, 19 had received cannabis treatment for indications such as sleep disorders, behavioral anomalies, and chorea. All but one patient reported an improvement in symptoms (94%). No adverse events were recorded, although one patient died from a COVID-19 infection.
Overall, medical cannabis appeared to safely relieve symptoms in patients with Huntington’s disease. A double-blind randomized controlled trial should further examine efficacy of these findings, the study authors recommended.
Mr. Goldberg had no disclosures or conflicts of interest in reporting his research.
FROM MDS 2022
Novel combination treatment improves function in early Parkinson’s disease
Results from a phase 3 trial found that P2B001 was superior to its components in improving motor symptoms and daily function and was comparable with marketed doses of pramipexole.
P2B001 also produced less daytime sleepiness and fewer dopaminergic effects, said the investigators, who presented findings at the International Congress of Parkinson’s Disease and Movement Disorders.
The treatment studied, P2B001, is a proprietary, fixed-dose combination of extended-release (ER) formulations of pramipexole and rasagiline. Neither dose is currently available on the market.
Investigators wanted to test the hypothesis that two anti-Parkinsonian drugs that act through different mechanisms could work synergistically, providing benefits comparable with pramipexole but with fewer side effects, said lead study author Warren Olanow, MD, professor emeritus in the neurology and neuroscience departments at the Icahn School of Medicine at Mount Sinai, New York.
Pramipexole is problematic in that it causes dopaminergic and sleep-related side effects.
Laboratory studies have shown that low doses of pramipexole and rasagiline act synergistically, said Dr. Olanow. “A previous double-blind controlled study demonstrated that P2B001 was significantly superior to placebo with respect to efficacy (P < .001) and had a good safety and tolerability profile.”
P2B001 outperforms other formulations
The multicenter phase 3 study (NCT03329508) enrolled 544 patients aged 35-80 with early Parkinson’s disease to assess efficacy and safety of a daily dose of P2B001, compared with its components. Patients were randomized 2:2:2:1 to 12 weeks of treatment with P2B001; pramipexole ER 0.6 mg; rasagiline ER 0.75 mg, or to a calibration arm of marketed pramipexole-ER titrated to optimal dose (mean dose, 3.2 mg).
The primary endpoint compared baseline with week 12 changes in Unified Parkinson’s Disease Rating Scale total scores for P2B001 versus its individual components. The secondary endpoint compared baseline changes in Epworth Sleepiness Scale (ESS) for P2B001 versus pramipexole-ER.
P2B001 showed superior efficacy to each of its individual components and comparable efficacy with marketed doses of pramipexole-ER. It also yielded fewer adverse events related to dopaminergic side effects and less daytime sleepiness as measured by ESS. “Further, the drug is administered once a day and does not require titration,” said Dr. Olanow.
Levodopa-related benefits
Another advantage of starting early-stage patients on P2B001 is that it would give patients more time to be on an effective therapy with fewer side effects before going on levodopa, the current gold standard for Parkinson’s disease treatment.
Although the American Academy of Neurology recommends levodopa as initial therapy for Parkinson’s disease, the drug has been associated with a risk of developing motor complications.
“This opinion, however, was formulated prior to the availability of the results of the P2B001 study and should be reassessed in the light of the present study,” said Dr. Olanow. Longer-term studies should assess when and if patients will require levodopa therapy, as well as the long-term effects of P2B001 on the development of motor complications in patients with early Parkinson’s disease patients.
Investigators are preparing a regulatory market approval filing for P2B001 with the Food and Drug Administration.
Dr. Olanow is CEO of Clintrex Research Corporation, which has provided services to Pharma2B, sponsor of the phase 3 study. Pharma Two B is a private, late clinical-stage pharmaceutical company in Rehovot, Israel, that owns worldwide granted patents for P2B001 pharmaceutical composition and method of treatment.
Results from a phase 3 trial found that P2B001 was superior to its components in improving motor symptoms and daily function and was comparable with marketed doses of pramipexole.
P2B001 also produced less daytime sleepiness and fewer dopaminergic effects, said the investigators, who presented findings at the International Congress of Parkinson’s Disease and Movement Disorders.
The treatment studied, P2B001, is a proprietary, fixed-dose combination of extended-release (ER) formulations of pramipexole and rasagiline. Neither dose is currently available on the market.
Investigators wanted to test the hypothesis that two anti-Parkinsonian drugs that act through different mechanisms could work synergistically, providing benefits comparable with pramipexole but with fewer side effects, said lead study author Warren Olanow, MD, professor emeritus in the neurology and neuroscience departments at the Icahn School of Medicine at Mount Sinai, New York.
Pramipexole is problematic in that it causes dopaminergic and sleep-related side effects.
Laboratory studies have shown that low doses of pramipexole and rasagiline act synergistically, said Dr. Olanow. “A previous double-blind controlled study demonstrated that P2B001 was significantly superior to placebo with respect to efficacy (P < .001) and had a good safety and tolerability profile.”
P2B001 outperforms other formulations
The multicenter phase 3 study (NCT03329508) enrolled 544 patients aged 35-80 with early Parkinson’s disease to assess efficacy and safety of a daily dose of P2B001, compared with its components. Patients were randomized 2:2:2:1 to 12 weeks of treatment with P2B001; pramipexole ER 0.6 mg; rasagiline ER 0.75 mg, or to a calibration arm of marketed pramipexole-ER titrated to optimal dose (mean dose, 3.2 mg).
The primary endpoint compared baseline with week 12 changes in Unified Parkinson’s Disease Rating Scale total scores for P2B001 versus its individual components. The secondary endpoint compared baseline changes in Epworth Sleepiness Scale (ESS) for P2B001 versus pramipexole-ER.
P2B001 showed superior efficacy to each of its individual components and comparable efficacy with marketed doses of pramipexole-ER. It also yielded fewer adverse events related to dopaminergic side effects and less daytime sleepiness as measured by ESS. “Further, the drug is administered once a day and does not require titration,” said Dr. Olanow.
Levodopa-related benefits
Another advantage of starting early-stage patients on P2B001 is that it would give patients more time to be on an effective therapy with fewer side effects before going on levodopa, the current gold standard for Parkinson’s disease treatment.
Although the American Academy of Neurology recommends levodopa as initial therapy for Parkinson’s disease, the drug has been associated with a risk of developing motor complications.
“This opinion, however, was formulated prior to the availability of the results of the P2B001 study and should be reassessed in the light of the present study,” said Dr. Olanow. Longer-term studies should assess when and if patients will require levodopa therapy, as well as the long-term effects of P2B001 on the development of motor complications in patients with early Parkinson’s disease patients.
Investigators are preparing a regulatory market approval filing for P2B001 with the Food and Drug Administration.
Dr. Olanow is CEO of Clintrex Research Corporation, which has provided services to Pharma2B, sponsor of the phase 3 study. Pharma Two B is a private, late clinical-stage pharmaceutical company in Rehovot, Israel, that owns worldwide granted patents for P2B001 pharmaceutical composition and method of treatment.
Results from a phase 3 trial found that P2B001 was superior to its components in improving motor symptoms and daily function and was comparable with marketed doses of pramipexole.
P2B001 also produced less daytime sleepiness and fewer dopaminergic effects, said the investigators, who presented findings at the International Congress of Parkinson’s Disease and Movement Disorders.
The treatment studied, P2B001, is a proprietary, fixed-dose combination of extended-release (ER) formulations of pramipexole and rasagiline. Neither dose is currently available on the market.
Investigators wanted to test the hypothesis that two anti-Parkinsonian drugs that act through different mechanisms could work synergistically, providing benefits comparable with pramipexole but with fewer side effects, said lead study author Warren Olanow, MD, professor emeritus in the neurology and neuroscience departments at the Icahn School of Medicine at Mount Sinai, New York.
Pramipexole is problematic in that it causes dopaminergic and sleep-related side effects.
Laboratory studies have shown that low doses of pramipexole and rasagiline act synergistically, said Dr. Olanow. “A previous double-blind controlled study demonstrated that P2B001 was significantly superior to placebo with respect to efficacy (P < .001) and had a good safety and tolerability profile.”
P2B001 outperforms other formulations
The multicenter phase 3 study (NCT03329508) enrolled 544 patients aged 35-80 with early Parkinson’s disease to assess efficacy and safety of a daily dose of P2B001, compared with its components. Patients were randomized 2:2:2:1 to 12 weeks of treatment with P2B001; pramipexole ER 0.6 mg; rasagiline ER 0.75 mg, or to a calibration arm of marketed pramipexole-ER titrated to optimal dose (mean dose, 3.2 mg).
The primary endpoint compared baseline with week 12 changes in Unified Parkinson’s Disease Rating Scale total scores for P2B001 versus its individual components. The secondary endpoint compared baseline changes in Epworth Sleepiness Scale (ESS) for P2B001 versus pramipexole-ER.
P2B001 showed superior efficacy to each of its individual components and comparable efficacy with marketed doses of pramipexole-ER. It also yielded fewer adverse events related to dopaminergic side effects and less daytime sleepiness as measured by ESS. “Further, the drug is administered once a day and does not require titration,” said Dr. Olanow.
Levodopa-related benefits
Another advantage of starting early-stage patients on P2B001 is that it would give patients more time to be on an effective therapy with fewer side effects before going on levodopa, the current gold standard for Parkinson’s disease treatment.
Although the American Academy of Neurology recommends levodopa as initial therapy for Parkinson’s disease, the drug has been associated with a risk of developing motor complications.
“This opinion, however, was formulated prior to the availability of the results of the P2B001 study and should be reassessed in the light of the present study,” said Dr. Olanow. Longer-term studies should assess when and if patients will require levodopa therapy, as well as the long-term effects of P2B001 on the development of motor complications in patients with early Parkinson’s disease patients.
Investigators are preparing a regulatory market approval filing for P2B001 with the Food and Drug Administration.
Dr. Olanow is CEO of Clintrex Research Corporation, which has provided services to Pharma2B, sponsor of the phase 3 study. Pharma Two B is a private, late clinical-stage pharmaceutical company in Rehovot, Israel, that owns worldwide granted patents for P2B001 pharmaceutical composition and method of treatment.
From MDS 2022
OMERACT continues to set standards on research outcomes, enhancing the patient voice
Clinical research in rheumatology was suffering from an identity crisis of sorts 40 years ago. A lack of consensus across continents resulted in differing views about clinical outcome measures and judgments about treatments.
Patients were not allowed to be the generating source of a clinical outcome, according to Peter Tugwell, MSc, MD. “The only outcomes that were acceptable were clinician assessments, blood tests, and imaging,” said Dr. Tugwell, professor of medicine, epidemiology, and public health at the University of Ottawa (Ont.) and a practicing rheumatologist at Ottawa Hospital.
Clinicians were coming to different conclusions about patient responses to treatment when managing rheumatoid arthritis in clinical practice.
OMERACT sought to address this lack of uniformity. This international group, formed in 1992, leverages stakeholder groups to improve outcome measurement in rheumatology endpoints through a consensus-building, data-driven format.
It was originally known as “Outcome Measures in Rheumatoid Arthritis Clinical Trials,” but its leaders have since broadened its scope to “Outcome Measures in Rheumatology.” Over the years, it has evolved into an international network that assesses measurement across a wide variety of intervention studies. Now 30 years old, the network spans 40 active working groups and has influenced work in patient outcomes across 500 peer-reviewed publications.
The network meets every 2 years to address what is always a challenging agenda, said Dr. Tugwell, one of its founding members and chair. “There’s lots of strong opinions.” Participating in the discussions are individuals from all stages of seniority in rheumatology and clinical epidemiology, patient research partners, industry, approval agencies, and many countries who are committed to the spirit of OMERACT.
“The secret to our success has been getting world leaders to come together and have those discussions, work them through, and identify common ground in such a way that the approval agencies accept these outcome measures in clinical trials,” he added.
“My impression was the founders perceived a problem in the early 1990s and devised a consensus method in an attempt to quantify clinical parameters to define disease activity in rheumatoid arthritis – an important first step to do clinical trials and allow comparisons between them,” said Patricia Woo, CBE, FMedSci, FRCP, emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. At that time, even disease definitions varied between the United States and Europe and other parts of the world, said Dr. Woo, who is not a part of OMERACT. “This was especially true for pediatric rheumatology.”
Fusing the continental divide
OMERACT arose from a need to streamline clinical outcome measures in rheumatology. Research papers during the 1980s demonstrated a lack of coherence in managing patients with rheumatoid arthritis in routine practice. In addition, the measures used to define clinical endpoints in clinical trials operated in silos – they were either too specific to a certain trial, overlapped with other concepts, or didn’t reflect changes in treatment.
Approval agencies in Europe and North America were approving only outcomes measures developed by their respective researchers. This was also true of patients they tested on. “This seemed crazy,” Dr. Tugwell said.
Dr. Tugwell was involved in the Cochrane collaboration, which conducts systematic reviews of best evidence across the world that assesses the magnitude of benefits versus harms.
To achieve this goal, “you need to pull studies from around the world,” he said. Maarten Boers, MD, PhD, a rheumatologist (and later professor of clinical epidemiology at Amsterdam University Medical Center) from the Netherlands, spent a year in Ontario, Canada, to train as a clinical epidemiologist. Together, Dr. Tugwell and Dr. Boers began discussing options to develop more streamlined outcome measures.
They initiated the first OMERACT conference in Maastricht, the Netherlands, in 1992. The Food and Drug Administration and European Medicines Agency participated, along with leaders of outcomes measurement in Europe and in North America.
Discussions centered on methods to develop outcomes in a meaningful fashion. During the first meeting, North American and European approval agencies agreed to accept each other’s studies and endpoints and patient reported outcomes.
Agreement was achieved on a preliminary set of outcome domains and measures that later became known as the WHO-ILAR (World Health Organization–International League of Associations for Rheumatology) core set. The set included seven outcome domains: tender joints, swollen joints, pain, physician global assessment, patient global assessment, physical disability, and acute phase reactants, and one additional outcome domain for studies lasting 1 year or more: radiographs of the joints.
“A proactive program was planned to test not only the validity of these endpoints, but also the methods for their measurement. This was the start of a continuing process,” OMERACT members said in a joint statement for this article. Meetings have since taken place every 2 years.
OMERACT accomplishments
OMERACT now requires buy-in from four continents: Asia, Australia, Europe, and North America.
Its leaders have developed an explicit process for gaining endorsement of core outcome domains and instrument measurement sets. To fully capture the possibilities of “what to measure,” i.e., “measurable aspects of health conditions,” OMERACT has developed a framework of concepts, core areas, and outcome domains. The key concepts are pathophysiology (with a core area termed “manifestations/abnormalities”) and impact (with core areas of “death/lifespan,” and “life impact,” and the optional area of “societal/resource use”). An outcome domain defines an element of a core area to measure the effects of a treatment, such as blood markers, pain intensity, physical function, or emotional well-being.
A core outcome domain set is developed by agreeing to at least one outcome domain within one of the three core areas. Subsequently, a core outcome measurement set is developed by agreeing to at least one applicable measurement instrument for each core outcome domain. This requires documentation of validity, summarized under three metrics: truth, discrimination, and feasibility.
OMERACT’s handbook provides tutelage on establishing and implementing core outcomes, and several workbooks offer guidance on developing core outcome domain sets, selecting instruments for core outcome measurement sets, and OMERACT methodology.
All this work has led to widespread adoption.
Approval agencies have accepted OMERACT’s filter and methods advances, which have been adopted by many research groups in rheumatology and among nonrheumatology research groups. Organizations such as the U.S. National Institutes of Health’s National Institute of Neurological Disorders and Stroke have sought its advice.
Its core outcomes have been adopted and used for approval in the great majority of studies on rheumatoid arthritis, Dr. Tugwell said.
Several BMJ articles underscore the influence and uptake of OMERACT’s core outcome set. One 2017 paper, which analyzed 273 randomized trials of rheumatoid arthritis drug treatments on ClinicalTrials.gov, found that the WHO-ILAR arthritis core outcome set was reported in 81% of the studies. “The adoption of a core outcome set has the potential to increase consistency in outcomes measured across trials and ensure that trials are more likely to measure appropriate outcomes,” the authors concluded.
Since the initial 1992 meeting, OMERACT has broadened its focus from rheumatoid arthritis to 25 other musculoskeletal conditions.
For example, other OMERACT conferences have led to consensus on core sets of measures for osteoarthritis and osteoporosis, psoriasis/psoriatic arthritis, psychosocial measures, and a core set of data for cost-effectiveness evaluations.
‘Speed is a limitation’
OMERACT is a bottom-up volunteer organization. It doesn’t represent any official organization of any clinical society. “We’ve not asked to be adopted by the American College of Rheumatology, EULAR [European Alliance of Associations for Rheumatology], or other international organizations,” Dr. Tugwell said. It offers a chance for patients, users, and doers of research to work together to agree on rigorous criteria accepted by the approval agencies and take the necessary time to work things through.
This is not a fast process, usually taking 4-6 years to initiate and establish an outcome domain set, he emphasized. “It would be beneficial to do it faster if we had the resources to meet every year. The fact is we’re a volunteer organization that meets every 2 years.”
Speed is a limitation, he acknowledged, but it’s an acceptable trade-off for doing things correctly.
The group has faced other challenges during the COVID-19 pandemic, pivoting to a virtual format that had benefits and limitations.
In one respect, moving to a virtual meeting increased uptake in participation and voting, Dr. Tugwell said. Patient participants with severe rheumatoid arthritis no longer faced the challenges of travel. “On the other hand, we didn’t have the same opportunity to achieve common ground virtually,” he said. “Where there are strong disagreements, I’m a great believer that people need to know one another. There needs to be relationship building.”
OMERACT’s emerging leader program has been a cornerstone of its in-person meetings, engaging young rheumatologists to interact with some of the leaders of outcome measurement. The virtual format dampened this process somewhat, eliminating those important “café chats” between the stakeholders.
The hope is to bring people face-to-face once more at the next meeting in May 2023. The agenda will focus on relationship building, identifying controversial areas, and bringing younger people to develop relationships, Dr. Tugwell said. OMERACT will retain a virtual option for the worldwide voting, “which will allow for more buy-in from so many more people,” he added.
A consensus on pain
The onus of developing outcome measures that move with the times is sometimes too great for one group to manage. In 2018, OMERACT became a part of the Red Hat Group (RHG), an organization conceived at the COMET (Core Outcome Measures in Effectiveness Trials) VII meeting in Amsterdam.
RHG aims to improve the choice of outcomes in health research. It includes eight groups: COMET; OMERACT; the Cochrane Skin Core Outcome Set Initiative; Grading of Recommendations, Assessment, Development and Evaluations; Center for Medical Technology Policy; COnsensus-based Standards for the selection of health Measurement Instruments; Clinical Data Interchange Standards Consortium; and Standardized Outcomes in Nephrology.
The collaboration between groups offers a “very interesting interface between consensus building as well as hard evidence,” Dr. Tugwell said. The focus goes beyond rheumatology to other clinical areas of common interest, exploring how one classifies outcome domains in terms of symptoms, life impact, or death.
Pain is an important common denominator that the RHG has evaluated.
“We believe it’s too general. We’re trying to define pain across all Red Hat Groups because it’s clear that the research community has all these different scales for defining pain severity,” Dr. Tugwell said. “We have to find a way to make ruthless decisions and rules for doing it. And of course, it has to be transparent.”
Looking ahead
As part of its ongoing work, OMERACT is evaluating the robustness of instruments that rheumatologists use as outcome measures in clinical trials, which can be a laborious process. The OMERACT Filter 2.0, part of the latest iteration of the handbook, offers strong guidance for researchers but needs a long-term strategy and key methodological support. “To that end, we set up a technical advisory group to help people in the instrument selection work and that remains an ongoing process,” OMERACT leaders said in their joint statement.
OMERACT is looking at opportunities to create benchmark processes for developing core sets outside of rheumatology and a methodology around outcome measures such as contextual factors, composites, and surrogates.
It will also be taking a step back to solicit opinions from the approval agencies represented by the OMERACT membership on the OMERACT handbook.
The goal is to make sure the handbook aligns with everyone else’s approval and labeling requirements.
OMERACT’s patient participants bring important perspectives
OMERACT over the years has sought to become a more patient-centered group. Patients have been involved in OMERACT activities since its sixth meeting, forming an independent, yet integrated, group within the network. They have their own steering committee and produced and helped to update a glossary for OMERACT patients and professionals.
Catherine (McGowan) Hofstetter, who was diagnosed with rheumatoid arthritis 30 years ago, chairs OMERACT’s Patient Research Partners Support Team. In a Q&A, she discussed the importance of patient voices and OMERACT’s plans to further educate and include patients in the dialogue on outcomes.
Question: Have patients always been a part of OMERACT meetings?
Answer: Patients have been involved with OMERACT since 2002. The patient voice adds relevance to all the work that OMERACT does. You can’t begin to talk about outcomes unless there is a patient at the table with lived experience.
Q: Can you cite a few examples of how the patient voice enriches the conversation on outcomes research?
A: Outcomes and priorities that are important to patients are often completely different than those of the clinician. For instance, a work outcome is important to someone who doesn’t have any medical insurance or disability insurance, so that you can ensure that there is food on the table and a roof over your head. Or it may be important to someone because the employment provides medical and disability insurance to provide security for them and their family. These are two different perspectives on work and therefore work priorities and outcomes.
Q: What have been some of the challenges of getting patients to participate?
A: Training patients is one challenge. OMERACT’s work has a very steep learning curve, and while the basics are the same between the groups in terms of looking at what we measure and how we measure it, the nuances of different working groups require a lot of time and energy to be comfortable enough with the work, and then be confident enough to bring your perspective and lived experience to the table. It’s also a very accomplished group, which can be quite intimidating. Self-disclosure is a very personal and intimate undertaking that requires patience, compassion, and respect.
Q: Are there any plans to enhance patient engagement?
A: When we had OMERACT 2020 it was a virtual conference that took place over about 6 months. We had far more patient research partners [PRPs] participate than we have ever had at any OMERACT face-to-face meeting. There is a desire and passion on the part of patients to lend their voices to the work. The working groups meet virtually throughout the year to advance their agendas, and PRPs are a part of each of the working groups.
Hopefully, we can start working toward including more voices at the conferences by enabling a hybrid model. The PRP Support Team will begin engaging patients this fall with education, mentoring, and team-building exercises so by the time we meet in person in May 2023, they will have enough background knowledge and information to give them the confidence that will enhance their experience at the face-to-face meeting.
We also need to ensure that those patients who want to stay engaged can. This means that the education and training should continue long after the face-to-face meeting is over. We need to build capacity in the PRP group and look to succession planning and be a resource to working groups struggling to find PRPs to work with them on a longer-term basis.
Clinical research in rheumatology was suffering from an identity crisis of sorts 40 years ago. A lack of consensus across continents resulted in differing views about clinical outcome measures and judgments about treatments.
Patients were not allowed to be the generating source of a clinical outcome, according to Peter Tugwell, MSc, MD. “The only outcomes that were acceptable were clinician assessments, blood tests, and imaging,” said Dr. Tugwell, professor of medicine, epidemiology, and public health at the University of Ottawa (Ont.) and a practicing rheumatologist at Ottawa Hospital.
Clinicians were coming to different conclusions about patient responses to treatment when managing rheumatoid arthritis in clinical practice.
OMERACT sought to address this lack of uniformity. This international group, formed in 1992, leverages stakeholder groups to improve outcome measurement in rheumatology endpoints through a consensus-building, data-driven format.
It was originally known as “Outcome Measures in Rheumatoid Arthritis Clinical Trials,” but its leaders have since broadened its scope to “Outcome Measures in Rheumatology.” Over the years, it has evolved into an international network that assesses measurement across a wide variety of intervention studies. Now 30 years old, the network spans 40 active working groups and has influenced work in patient outcomes across 500 peer-reviewed publications.
The network meets every 2 years to address what is always a challenging agenda, said Dr. Tugwell, one of its founding members and chair. “There’s lots of strong opinions.” Participating in the discussions are individuals from all stages of seniority in rheumatology and clinical epidemiology, patient research partners, industry, approval agencies, and many countries who are committed to the spirit of OMERACT.
“The secret to our success has been getting world leaders to come together and have those discussions, work them through, and identify common ground in such a way that the approval agencies accept these outcome measures in clinical trials,” he added.
“My impression was the founders perceived a problem in the early 1990s and devised a consensus method in an attempt to quantify clinical parameters to define disease activity in rheumatoid arthritis – an important first step to do clinical trials and allow comparisons between them,” said Patricia Woo, CBE, FMedSci, FRCP, emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. At that time, even disease definitions varied between the United States and Europe and other parts of the world, said Dr. Woo, who is not a part of OMERACT. “This was especially true for pediatric rheumatology.”
Fusing the continental divide
OMERACT arose from a need to streamline clinical outcome measures in rheumatology. Research papers during the 1980s demonstrated a lack of coherence in managing patients with rheumatoid arthritis in routine practice. In addition, the measures used to define clinical endpoints in clinical trials operated in silos – they were either too specific to a certain trial, overlapped with other concepts, or didn’t reflect changes in treatment.
Approval agencies in Europe and North America were approving only outcomes measures developed by their respective researchers. This was also true of patients they tested on. “This seemed crazy,” Dr. Tugwell said.
Dr. Tugwell was involved in the Cochrane collaboration, which conducts systematic reviews of best evidence across the world that assesses the magnitude of benefits versus harms.
To achieve this goal, “you need to pull studies from around the world,” he said. Maarten Boers, MD, PhD, a rheumatologist (and later professor of clinical epidemiology at Amsterdam University Medical Center) from the Netherlands, spent a year in Ontario, Canada, to train as a clinical epidemiologist. Together, Dr. Tugwell and Dr. Boers began discussing options to develop more streamlined outcome measures.
They initiated the first OMERACT conference in Maastricht, the Netherlands, in 1992. The Food and Drug Administration and European Medicines Agency participated, along with leaders of outcomes measurement in Europe and in North America.
Discussions centered on methods to develop outcomes in a meaningful fashion. During the first meeting, North American and European approval agencies agreed to accept each other’s studies and endpoints and patient reported outcomes.
Agreement was achieved on a preliminary set of outcome domains and measures that later became known as the WHO-ILAR (World Health Organization–International League of Associations for Rheumatology) core set. The set included seven outcome domains: tender joints, swollen joints, pain, physician global assessment, patient global assessment, physical disability, and acute phase reactants, and one additional outcome domain for studies lasting 1 year or more: radiographs of the joints.
“A proactive program was planned to test not only the validity of these endpoints, but also the methods for their measurement. This was the start of a continuing process,” OMERACT members said in a joint statement for this article. Meetings have since taken place every 2 years.
OMERACT accomplishments
OMERACT now requires buy-in from four continents: Asia, Australia, Europe, and North America.
Its leaders have developed an explicit process for gaining endorsement of core outcome domains and instrument measurement sets. To fully capture the possibilities of “what to measure,” i.e., “measurable aspects of health conditions,” OMERACT has developed a framework of concepts, core areas, and outcome domains. The key concepts are pathophysiology (with a core area termed “manifestations/abnormalities”) and impact (with core areas of “death/lifespan,” and “life impact,” and the optional area of “societal/resource use”). An outcome domain defines an element of a core area to measure the effects of a treatment, such as blood markers, pain intensity, physical function, or emotional well-being.
A core outcome domain set is developed by agreeing to at least one outcome domain within one of the three core areas. Subsequently, a core outcome measurement set is developed by agreeing to at least one applicable measurement instrument for each core outcome domain. This requires documentation of validity, summarized under three metrics: truth, discrimination, and feasibility.
OMERACT’s handbook provides tutelage on establishing and implementing core outcomes, and several workbooks offer guidance on developing core outcome domain sets, selecting instruments for core outcome measurement sets, and OMERACT methodology.
All this work has led to widespread adoption.
Approval agencies have accepted OMERACT’s filter and methods advances, which have been adopted by many research groups in rheumatology and among nonrheumatology research groups. Organizations such as the U.S. National Institutes of Health’s National Institute of Neurological Disorders and Stroke have sought its advice.
Its core outcomes have been adopted and used for approval in the great majority of studies on rheumatoid arthritis, Dr. Tugwell said.
Several BMJ articles underscore the influence and uptake of OMERACT’s core outcome set. One 2017 paper, which analyzed 273 randomized trials of rheumatoid arthritis drug treatments on ClinicalTrials.gov, found that the WHO-ILAR arthritis core outcome set was reported in 81% of the studies. “The adoption of a core outcome set has the potential to increase consistency in outcomes measured across trials and ensure that trials are more likely to measure appropriate outcomes,” the authors concluded.
Since the initial 1992 meeting, OMERACT has broadened its focus from rheumatoid arthritis to 25 other musculoskeletal conditions.
For example, other OMERACT conferences have led to consensus on core sets of measures for osteoarthritis and osteoporosis, psoriasis/psoriatic arthritis, psychosocial measures, and a core set of data for cost-effectiveness evaluations.
‘Speed is a limitation’
OMERACT is a bottom-up volunteer organization. It doesn’t represent any official organization of any clinical society. “We’ve not asked to be adopted by the American College of Rheumatology, EULAR [European Alliance of Associations for Rheumatology], or other international organizations,” Dr. Tugwell said. It offers a chance for patients, users, and doers of research to work together to agree on rigorous criteria accepted by the approval agencies and take the necessary time to work things through.
This is not a fast process, usually taking 4-6 years to initiate and establish an outcome domain set, he emphasized. “It would be beneficial to do it faster if we had the resources to meet every year. The fact is we’re a volunteer organization that meets every 2 years.”
Speed is a limitation, he acknowledged, but it’s an acceptable trade-off for doing things correctly.
The group has faced other challenges during the COVID-19 pandemic, pivoting to a virtual format that had benefits and limitations.
In one respect, moving to a virtual meeting increased uptake in participation and voting, Dr. Tugwell said. Patient participants with severe rheumatoid arthritis no longer faced the challenges of travel. “On the other hand, we didn’t have the same opportunity to achieve common ground virtually,” he said. “Where there are strong disagreements, I’m a great believer that people need to know one another. There needs to be relationship building.”
OMERACT’s emerging leader program has been a cornerstone of its in-person meetings, engaging young rheumatologists to interact with some of the leaders of outcome measurement. The virtual format dampened this process somewhat, eliminating those important “café chats” between the stakeholders.
The hope is to bring people face-to-face once more at the next meeting in May 2023. The agenda will focus on relationship building, identifying controversial areas, and bringing younger people to develop relationships, Dr. Tugwell said. OMERACT will retain a virtual option for the worldwide voting, “which will allow for more buy-in from so many more people,” he added.
A consensus on pain
The onus of developing outcome measures that move with the times is sometimes too great for one group to manage. In 2018, OMERACT became a part of the Red Hat Group (RHG), an organization conceived at the COMET (Core Outcome Measures in Effectiveness Trials) VII meeting in Amsterdam.
RHG aims to improve the choice of outcomes in health research. It includes eight groups: COMET; OMERACT; the Cochrane Skin Core Outcome Set Initiative; Grading of Recommendations, Assessment, Development and Evaluations; Center for Medical Technology Policy; COnsensus-based Standards for the selection of health Measurement Instruments; Clinical Data Interchange Standards Consortium; and Standardized Outcomes in Nephrology.
The collaboration between groups offers a “very interesting interface between consensus building as well as hard evidence,” Dr. Tugwell said. The focus goes beyond rheumatology to other clinical areas of common interest, exploring how one classifies outcome domains in terms of symptoms, life impact, or death.
Pain is an important common denominator that the RHG has evaluated.
“We believe it’s too general. We’re trying to define pain across all Red Hat Groups because it’s clear that the research community has all these different scales for defining pain severity,” Dr. Tugwell said. “We have to find a way to make ruthless decisions and rules for doing it. And of course, it has to be transparent.”
Looking ahead
As part of its ongoing work, OMERACT is evaluating the robustness of instruments that rheumatologists use as outcome measures in clinical trials, which can be a laborious process. The OMERACT Filter 2.0, part of the latest iteration of the handbook, offers strong guidance for researchers but needs a long-term strategy and key methodological support. “To that end, we set up a technical advisory group to help people in the instrument selection work and that remains an ongoing process,” OMERACT leaders said in their joint statement.
OMERACT is looking at opportunities to create benchmark processes for developing core sets outside of rheumatology and a methodology around outcome measures such as contextual factors, composites, and surrogates.
It will also be taking a step back to solicit opinions from the approval agencies represented by the OMERACT membership on the OMERACT handbook.
The goal is to make sure the handbook aligns with everyone else’s approval and labeling requirements.
OMERACT’s patient participants bring important perspectives
OMERACT over the years has sought to become a more patient-centered group. Patients have been involved in OMERACT activities since its sixth meeting, forming an independent, yet integrated, group within the network. They have their own steering committee and produced and helped to update a glossary for OMERACT patients and professionals.
Catherine (McGowan) Hofstetter, who was diagnosed with rheumatoid arthritis 30 years ago, chairs OMERACT’s Patient Research Partners Support Team. In a Q&A, she discussed the importance of patient voices and OMERACT’s plans to further educate and include patients in the dialogue on outcomes.
Question: Have patients always been a part of OMERACT meetings?
Answer: Patients have been involved with OMERACT since 2002. The patient voice adds relevance to all the work that OMERACT does. You can’t begin to talk about outcomes unless there is a patient at the table with lived experience.
Q: Can you cite a few examples of how the patient voice enriches the conversation on outcomes research?
A: Outcomes and priorities that are important to patients are often completely different than those of the clinician. For instance, a work outcome is important to someone who doesn’t have any medical insurance or disability insurance, so that you can ensure that there is food on the table and a roof over your head. Or it may be important to someone because the employment provides medical and disability insurance to provide security for them and their family. These are two different perspectives on work and therefore work priorities and outcomes.
Q: What have been some of the challenges of getting patients to participate?
A: Training patients is one challenge. OMERACT’s work has a very steep learning curve, and while the basics are the same between the groups in terms of looking at what we measure and how we measure it, the nuances of different working groups require a lot of time and energy to be comfortable enough with the work, and then be confident enough to bring your perspective and lived experience to the table. It’s also a very accomplished group, which can be quite intimidating. Self-disclosure is a very personal and intimate undertaking that requires patience, compassion, and respect.
Q: Are there any plans to enhance patient engagement?
A: When we had OMERACT 2020 it was a virtual conference that took place over about 6 months. We had far more patient research partners [PRPs] participate than we have ever had at any OMERACT face-to-face meeting. There is a desire and passion on the part of patients to lend their voices to the work. The working groups meet virtually throughout the year to advance their agendas, and PRPs are a part of each of the working groups.
Hopefully, we can start working toward including more voices at the conferences by enabling a hybrid model. The PRP Support Team will begin engaging patients this fall with education, mentoring, and team-building exercises so by the time we meet in person in May 2023, they will have enough background knowledge and information to give them the confidence that will enhance their experience at the face-to-face meeting.
We also need to ensure that those patients who want to stay engaged can. This means that the education and training should continue long after the face-to-face meeting is over. We need to build capacity in the PRP group and look to succession planning and be a resource to working groups struggling to find PRPs to work with them on a longer-term basis.
Clinical research in rheumatology was suffering from an identity crisis of sorts 40 years ago. A lack of consensus across continents resulted in differing views about clinical outcome measures and judgments about treatments.
Patients were not allowed to be the generating source of a clinical outcome, according to Peter Tugwell, MSc, MD. “The only outcomes that were acceptable were clinician assessments, blood tests, and imaging,” said Dr. Tugwell, professor of medicine, epidemiology, and public health at the University of Ottawa (Ont.) and a practicing rheumatologist at Ottawa Hospital.
Clinicians were coming to different conclusions about patient responses to treatment when managing rheumatoid arthritis in clinical practice.
OMERACT sought to address this lack of uniformity. This international group, formed in 1992, leverages stakeholder groups to improve outcome measurement in rheumatology endpoints through a consensus-building, data-driven format.
It was originally known as “Outcome Measures in Rheumatoid Arthritis Clinical Trials,” but its leaders have since broadened its scope to “Outcome Measures in Rheumatology.” Over the years, it has evolved into an international network that assesses measurement across a wide variety of intervention studies. Now 30 years old, the network spans 40 active working groups and has influenced work in patient outcomes across 500 peer-reviewed publications.
The network meets every 2 years to address what is always a challenging agenda, said Dr. Tugwell, one of its founding members and chair. “There’s lots of strong opinions.” Participating in the discussions are individuals from all stages of seniority in rheumatology and clinical epidemiology, patient research partners, industry, approval agencies, and many countries who are committed to the spirit of OMERACT.
“The secret to our success has been getting world leaders to come together and have those discussions, work them through, and identify common ground in such a way that the approval agencies accept these outcome measures in clinical trials,” he added.
“My impression was the founders perceived a problem in the early 1990s and devised a consensus method in an attempt to quantify clinical parameters to define disease activity in rheumatoid arthritis – an important first step to do clinical trials and allow comparisons between them,” said Patricia Woo, CBE, FMedSci, FRCP, emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. At that time, even disease definitions varied between the United States and Europe and other parts of the world, said Dr. Woo, who is not a part of OMERACT. “This was especially true for pediatric rheumatology.”
Fusing the continental divide
OMERACT arose from a need to streamline clinical outcome measures in rheumatology. Research papers during the 1980s demonstrated a lack of coherence in managing patients with rheumatoid arthritis in routine practice. In addition, the measures used to define clinical endpoints in clinical trials operated in silos – they were either too specific to a certain trial, overlapped with other concepts, or didn’t reflect changes in treatment.
Approval agencies in Europe and North America were approving only outcomes measures developed by their respective researchers. This was also true of patients they tested on. “This seemed crazy,” Dr. Tugwell said.
Dr. Tugwell was involved in the Cochrane collaboration, which conducts systematic reviews of best evidence across the world that assesses the magnitude of benefits versus harms.
To achieve this goal, “you need to pull studies from around the world,” he said. Maarten Boers, MD, PhD, a rheumatologist (and later professor of clinical epidemiology at Amsterdam University Medical Center) from the Netherlands, spent a year in Ontario, Canada, to train as a clinical epidemiologist. Together, Dr. Tugwell and Dr. Boers began discussing options to develop more streamlined outcome measures.
They initiated the first OMERACT conference in Maastricht, the Netherlands, in 1992. The Food and Drug Administration and European Medicines Agency participated, along with leaders of outcomes measurement in Europe and in North America.
Discussions centered on methods to develop outcomes in a meaningful fashion. During the first meeting, North American and European approval agencies agreed to accept each other’s studies and endpoints and patient reported outcomes.
Agreement was achieved on a preliminary set of outcome domains and measures that later became known as the WHO-ILAR (World Health Organization–International League of Associations for Rheumatology) core set. The set included seven outcome domains: tender joints, swollen joints, pain, physician global assessment, patient global assessment, physical disability, and acute phase reactants, and one additional outcome domain for studies lasting 1 year or more: radiographs of the joints.
“A proactive program was planned to test not only the validity of these endpoints, but also the methods for their measurement. This was the start of a continuing process,” OMERACT members said in a joint statement for this article. Meetings have since taken place every 2 years.
OMERACT accomplishments
OMERACT now requires buy-in from four continents: Asia, Australia, Europe, and North America.
Its leaders have developed an explicit process for gaining endorsement of core outcome domains and instrument measurement sets. To fully capture the possibilities of “what to measure,” i.e., “measurable aspects of health conditions,” OMERACT has developed a framework of concepts, core areas, and outcome domains. The key concepts are pathophysiology (with a core area termed “manifestations/abnormalities”) and impact (with core areas of “death/lifespan,” and “life impact,” and the optional area of “societal/resource use”). An outcome domain defines an element of a core area to measure the effects of a treatment, such as blood markers, pain intensity, physical function, or emotional well-being.
A core outcome domain set is developed by agreeing to at least one outcome domain within one of the three core areas. Subsequently, a core outcome measurement set is developed by agreeing to at least one applicable measurement instrument for each core outcome domain. This requires documentation of validity, summarized under three metrics: truth, discrimination, and feasibility.
OMERACT’s handbook provides tutelage on establishing and implementing core outcomes, and several workbooks offer guidance on developing core outcome domain sets, selecting instruments for core outcome measurement sets, and OMERACT methodology.
All this work has led to widespread adoption.
Approval agencies have accepted OMERACT’s filter and methods advances, which have been adopted by many research groups in rheumatology and among nonrheumatology research groups. Organizations such as the U.S. National Institutes of Health’s National Institute of Neurological Disorders and Stroke have sought its advice.
Its core outcomes have been adopted and used for approval in the great majority of studies on rheumatoid arthritis, Dr. Tugwell said.
Several BMJ articles underscore the influence and uptake of OMERACT’s core outcome set. One 2017 paper, which analyzed 273 randomized trials of rheumatoid arthritis drug treatments on ClinicalTrials.gov, found that the WHO-ILAR arthritis core outcome set was reported in 81% of the studies. “The adoption of a core outcome set has the potential to increase consistency in outcomes measured across trials and ensure that trials are more likely to measure appropriate outcomes,” the authors concluded.
Since the initial 1992 meeting, OMERACT has broadened its focus from rheumatoid arthritis to 25 other musculoskeletal conditions.
For example, other OMERACT conferences have led to consensus on core sets of measures for osteoarthritis and osteoporosis, psoriasis/psoriatic arthritis, psychosocial measures, and a core set of data for cost-effectiveness evaluations.
‘Speed is a limitation’
OMERACT is a bottom-up volunteer organization. It doesn’t represent any official organization of any clinical society. “We’ve not asked to be adopted by the American College of Rheumatology, EULAR [European Alliance of Associations for Rheumatology], or other international organizations,” Dr. Tugwell said. It offers a chance for patients, users, and doers of research to work together to agree on rigorous criteria accepted by the approval agencies and take the necessary time to work things through.
This is not a fast process, usually taking 4-6 years to initiate and establish an outcome domain set, he emphasized. “It would be beneficial to do it faster if we had the resources to meet every year. The fact is we’re a volunteer organization that meets every 2 years.”
Speed is a limitation, he acknowledged, but it’s an acceptable trade-off for doing things correctly.
The group has faced other challenges during the COVID-19 pandemic, pivoting to a virtual format that had benefits and limitations.
In one respect, moving to a virtual meeting increased uptake in participation and voting, Dr. Tugwell said. Patient participants with severe rheumatoid arthritis no longer faced the challenges of travel. “On the other hand, we didn’t have the same opportunity to achieve common ground virtually,” he said. “Where there are strong disagreements, I’m a great believer that people need to know one another. There needs to be relationship building.”
OMERACT’s emerging leader program has been a cornerstone of its in-person meetings, engaging young rheumatologists to interact with some of the leaders of outcome measurement. The virtual format dampened this process somewhat, eliminating those important “café chats” between the stakeholders.
The hope is to bring people face-to-face once more at the next meeting in May 2023. The agenda will focus on relationship building, identifying controversial areas, and bringing younger people to develop relationships, Dr. Tugwell said. OMERACT will retain a virtual option for the worldwide voting, “which will allow for more buy-in from so many more people,” he added.
A consensus on pain
The onus of developing outcome measures that move with the times is sometimes too great for one group to manage. In 2018, OMERACT became a part of the Red Hat Group (RHG), an organization conceived at the COMET (Core Outcome Measures in Effectiveness Trials) VII meeting in Amsterdam.
RHG aims to improve the choice of outcomes in health research. It includes eight groups: COMET; OMERACT; the Cochrane Skin Core Outcome Set Initiative; Grading of Recommendations, Assessment, Development and Evaluations; Center for Medical Technology Policy; COnsensus-based Standards for the selection of health Measurement Instruments; Clinical Data Interchange Standards Consortium; and Standardized Outcomes in Nephrology.
The collaboration between groups offers a “very interesting interface between consensus building as well as hard evidence,” Dr. Tugwell said. The focus goes beyond rheumatology to other clinical areas of common interest, exploring how one classifies outcome domains in terms of symptoms, life impact, or death.
Pain is an important common denominator that the RHG has evaluated.
“We believe it’s too general. We’re trying to define pain across all Red Hat Groups because it’s clear that the research community has all these different scales for defining pain severity,” Dr. Tugwell said. “We have to find a way to make ruthless decisions and rules for doing it. And of course, it has to be transparent.”
Looking ahead
As part of its ongoing work, OMERACT is evaluating the robustness of instruments that rheumatologists use as outcome measures in clinical trials, which can be a laborious process. The OMERACT Filter 2.0, part of the latest iteration of the handbook, offers strong guidance for researchers but needs a long-term strategy and key methodological support. “To that end, we set up a technical advisory group to help people in the instrument selection work and that remains an ongoing process,” OMERACT leaders said in their joint statement.
OMERACT is looking at opportunities to create benchmark processes for developing core sets outside of rheumatology and a methodology around outcome measures such as contextual factors, composites, and surrogates.
It will also be taking a step back to solicit opinions from the approval agencies represented by the OMERACT membership on the OMERACT handbook.
The goal is to make sure the handbook aligns with everyone else’s approval and labeling requirements.
OMERACT’s patient participants bring important perspectives
OMERACT over the years has sought to become a more patient-centered group. Patients have been involved in OMERACT activities since its sixth meeting, forming an independent, yet integrated, group within the network. They have their own steering committee and produced and helped to update a glossary for OMERACT patients and professionals.
Catherine (McGowan) Hofstetter, who was diagnosed with rheumatoid arthritis 30 years ago, chairs OMERACT’s Patient Research Partners Support Team. In a Q&A, she discussed the importance of patient voices and OMERACT’s plans to further educate and include patients in the dialogue on outcomes.
Question: Have patients always been a part of OMERACT meetings?
Answer: Patients have been involved with OMERACT since 2002. The patient voice adds relevance to all the work that OMERACT does. You can’t begin to talk about outcomes unless there is a patient at the table with lived experience.
Q: Can you cite a few examples of how the patient voice enriches the conversation on outcomes research?
A: Outcomes and priorities that are important to patients are often completely different than those of the clinician. For instance, a work outcome is important to someone who doesn’t have any medical insurance or disability insurance, so that you can ensure that there is food on the table and a roof over your head. Or it may be important to someone because the employment provides medical and disability insurance to provide security for them and their family. These are two different perspectives on work and therefore work priorities and outcomes.
Q: What have been some of the challenges of getting patients to participate?
A: Training patients is one challenge. OMERACT’s work has a very steep learning curve, and while the basics are the same between the groups in terms of looking at what we measure and how we measure it, the nuances of different working groups require a lot of time and energy to be comfortable enough with the work, and then be confident enough to bring your perspective and lived experience to the table. It’s also a very accomplished group, which can be quite intimidating. Self-disclosure is a very personal and intimate undertaking that requires patience, compassion, and respect.
Q: Are there any plans to enhance patient engagement?
A: When we had OMERACT 2020 it was a virtual conference that took place over about 6 months. We had far more patient research partners [PRPs] participate than we have ever had at any OMERACT face-to-face meeting. There is a desire and passion on the part of patients to lend their voices to the work. The working groups meet virtually throughout the year to advance their agendas, and PRPs are a part of each of the working groups.
Hopefully, we can start working toward including more voices at the conferences by enabling a hybrid model. The PRP Support Team will begin engaging patients this fall with education, mentoring, and team-building exercises so by the time we meet in person in May 2023, they will have enough background knowledge and information to give them the confidence that will enhance their experience at the face-to-face meeting.
We also need to ensure that those patients who want to stay engaged can. This means that the education and training should continue long after the face-to-face meeting is over. We need to build capacity in the PRP group and look to succession planning and be a resource to working groups struggling to find PRPs to work with them on a longer-term basis.
Physicians urged to write indications on drug scripts as methotrexate users face new barriers with SCOTUS decision
.
The Court’s 5-4 decision in Dobbs v. Jackson Women’s Health Organization, which halted abortion procedures across the country, also appears to be affecting certain drug regimens. Reports have emerged that pharmacies are denying access to methotrexate (MTX), a drug often used in patients with arthritis or cancer, as well as psoriasis and other skin diseases. In very high doses, MTX it is used to terminate an ectopic pregnancy after miscarriage. The drug can also lead to birth defects.
“It’s happening all over,” Donald Miller, PharmD, professor of pharmacy practice at North Dakota State University, Fargo, said in an interview. “Pharmacists are reluctant to dispense it, and rheumatologists are reluctant to prescribe it because they’re afraid of going to jail.”
Becky Schwartz, a patient who takes MTX for lupus, recently tweeted that her physician’s office stopped prescribing the drug because it is considered an abortifacient. “I had care that made my disabled life easier, and [the Supreme Court] took that from me,” Ms. Schwartz wrote.
Prior to the Supreme Court’s ruling, physicians were concerned about the impact an overturning of the 1973 law would have on patient access to MTX and other prescription medications with abortifacient properties. Doctors in general are becoming afraid of prescribing anything that’s a teratogen, said Dr. Miller.
MTX is used far more often for autoimmune disease than as an abortifacient, said rheumatologist Kristen Young, MD, clinical assistant professor at the University of Arizona College of Medicine, Phoenix. It’s a slippery slope if states reacting to the Supreme Court ruling start regulating oral abortifacients, she added. Specifically, this will have a significant impact on patients with rheumatic disease.
Texas pharmacies target two drugs
MTX denials have caught the attention of health care organizations. “Uncertainty in financial and criminal liability for health care professionals in certain state laws and regulations are possibly compromising continuity of care and access [to] medications proven to be safe and effective by the Food and Drug Administration for these indications,” warned the American Pharmacists Association (APhA) in a statement to this news organization.
The APhA said that it was monitoring this situation to assess the effect on patients and pharmacists.
The Arthritis Foundation was made aware of challenges from patients in accessing their MTX prescription for managing their arthritis and shared a statement on the Foundation’s website.
In Texas, pharmacists can refuse to fill scripts for misoprostol and MTX, a combination used for medical abortions. According to the foundation, “Already there are reports that people in Texas who miscarry or take methotrexate for arthritis [are] having trouble getting their prescriptions filled.”
MTX, approved by the FDA in 1985, “is the absolute cornerstone of rheumatoid arthritis. We cannot deny our patients this incredibly valuable drug,” said John Reveille, MD, vice-chair for the department of medicine at the University of Texas McGovern School of Medicine and a member of the Arthritis Foundation expert panel, in an interview.
“While it’s true that methotrexate can be lethal to the fetus, misoprostol is much more likely to cause a spontaneous abortion, and the combination is especially effective,” he said.
“If you look at Cochrane clinical studies, the dose of misoprostol contained in certain combinations with NSAIDs [nonsteroidal anti-inflammatory drugs] can induce spontaneous abortions. It’s surprising that pharmacists are targeting methotrexate, an essential drug in arthritis treatment, when there are medications available that do not have this benefit that can by themselves cause loss of the fetus, such as mifepristone,” added Dr. Reveille.
The Dobbs ruling could also affect the ability of oncologists to provide lifesaving cancer care, according to Jason Westin, MD, an oncologist at the University of Texas MD Anderson Cancer Center in the department of lymphoma and myeloma.
“We have heard of medications with multiple indications, such as methotrexate, not being dispensed by pharmacies due to confusion regarding the intended use and potential consequences for the health care team,” he said in an interview.
Conflicting laws pose challenges for physicians
In North Dakota, inconsistencies in several laws are making it difficult for physicians and pharmacists to make decisions. “Lots of confusion can result when people pass laws against abortion. There’s sometimes no insight into the ramifications of those laws,” said Dr. Miller.
North Dakota approved a trigger law several years ago that makes abortion illegal 30 days after an overturning of Roe. However, another law that regulates abortion conflicts with the trigger law. “Some of the language will need clarification in the next legislative session,” he said.
APhA and other pharmacy associations strongly favor not interfering with the doctor- or pharmacist-patient relationship. The law needs to defer to appropriate care between doctor and patient, said Dr. Miller. State pharmacy associations in North Dakota are working with legislatures to clarify any exceptions in the law, he added.
Arizona lawmakers are trying to reconcile two abortion laws on the books. One, based on an 1864 territorial law, deems abortion illegal. In addition, a newly approved law bans abortions after 15 weeks. The latter will go into effect in September 2022. In both laws, a risk to the mother’s life is the only exception for abortion, said Dr. Young.
Denials aren’t widespread
Not all doctors are seeing MTX denials, but they’re worried about the future. “To date, we have not encountered difficulty in obtaining methotrexate based upon state abortion restrictions but are concerned that this could occur and result in dangerous delays in care,” said Dr. Westin.
Dr. Reveille, who practices rheumatology in Houston, has not yet received any complaints from patients. Things may be different in more rural parts of Texas, where pharmacists could be denying prescriptions based on religious issues, he offered.
It’s a little soon to see what repercussions may result from the Supreme Court ruling and state actions, said Dr. Reveille. “In Texas, we’re a bit ahead of the tidal wave.”
Access problems also haven’t shown up at the university clinic where Dr. Young practices. “In Arizona, it’s unclear if there would be a legal basis to refuse a person methotrexate on the basis that it can be used as an abortifacient,” she said.
Specificity is key in writing Rx scripts
Physicians can make things easier for patients by writing the indication and dose for the drug on the prescription slip. For example, a 10-mg script for MTX is not going to be used for an abortion, said Dr. Miller.
Rheumatologists in Texas have been doing this for some time, even before the Supreme Court ruling, said Fehmida Zahabi, MD, FACR, president of the Society of Texas Association of Rheumatology. For MTX prescriptions in premenopausal women, “patients are told their doctor needs to call the pharmacist. In the small print, we are asked to give a diagnosis to make sure we aren’t using it to terminate pregnancies,” said Dr. Zahabi.
She further noted that if the diagnosis is already indicated on the script, pharmacies generally won’t give patients a hard time.
Patients can also ask their physicians for a letter of medical necessity that confirms a drug’s use for a specific medical condition.
Mail order is another option if a local pharmacy won’t fill a prescription, said Dr. Miller. “This is legal unless a state makes it illegal to send an abortifacient across state lines,” he added.
Many medications used in rheumatic diseases are harmful in pregnancy, and it’s important to routinely discuss pregnancy risk and planning in the rheumatology clinic, said Dr. Young. This should include a thorough discussion and referral for long-acting reversible contraception in most cases, she suggested.
Actions at the federal, state level
President Joe Biden recently signed an executive order prompting federal regulators to protect access to medication abortions, among other steps to safeguard access to reproductive services.
In a statement on Twitter, the American College of Rheumatology (ACR) said that it was “ ... following this issue closely to determine if rheumatology providers and patients are experiencing any widespread difficulty accessing methotrexate or if any initial disruptions are potentially temporary and due to the independent actions of pharmacists trying to figure out what is and isn’t allowed where they practice.”
ACR has assembled a task force of medical and policy experts to determine the best course of action for patients.
The Arthritis Foundation also continues to monitor the situation, encouraging patients to call its hotline, said Steven Schultz, director of state legislative affairs, in an interview.
“We are analyzing how medication abortion could cause confusion on the part of providers or pharmacists dispensing the medication and what this means for specific patients,” said Mr. Schultz. Through a survey, the foundation hopes to get a better idea of what’s going on in the states at a macro level.
This may take some time, as states go through a process of lawsuits, injunctions, or coming into session to do something that may affect access to MTX, said Mr. Schultz.
Being involved in local advocacy is more important than ever, stressed Dr. Young. “Additionally, being plugged into what the ACR and other advocacy groups are doing on the national level is helpful as well to know the status of these medication access issues.”
Rheumatologists have a unique voice in this discussion, she added. “We guide our patients to stability for a safe pregnancy, and even with careful planning, we see patients who become critically ill during pregnancy and require lifesaving treatment, which at times can mean an abortion is necessary.”
Oncologists also advocate for their patients on a regular basis to make sure they have access to the care they need, said Dr. Westin. This situation with Roe is no different, he added. “We will continue to use our unique expertise to advocate for policies that assure access to high-quality, evidence-based care – and to help our patients overcome barriers that may interfere.”
Dr. Reveille participated on an advisory board with Eli Lilly in October 2021.
A version of this article first appeared on Medscape.com.
.
The Court’s 5-4 decision in Dobbs v. Jackson Women’s Health Organization, which halted abortion procedures across the country, also appears to be affecting certain drug regimens. Reports have emerged that pharmacies are denying access to methotrexate (MTX), a drug often used in patients with arthritis or cancer, as well as psoriasis and other skin diseases. In very high doses, MTX it is used to terminate an ectopic pregnancy after miscarriage. The drug can also lead to birth defects.
“It’s happening all over,” Donald Miller, PharmD, professor of pharmacy practice at North Dakota State University, Fargo, said in an interview. “Pharmacists are reluctant to dispense it, and rheumatologists are reluctant to prescribe it because they’re afraid of going to jail.”
Becky Schwartz, a patient who takes MTX for lupus, recently tweeted that her physician’s office stopped prescribing the drug because it is considered an abortifacient. “I had care that made my disabled life easier, and [the Supreme Court] took that from me,” Ms. Schwartz wrote.
Prior to the Supreme Court’s ruling, physicians were concerned about the impact an overturning of the 1973 law would have on patient access to MTX and other prescription medications with abortifacient properties. Doctors in general are becoming afraid of prescribing anything that’s a teratogen, said Dr. Miller.
MTX is used far more often for autoimmune disease than as an abortifacient, said rheumatologist Kristen Young, MD, clinical assistant professor at the University of Arizona College of Medicine, Phoenix. It’s a slippery slope if states reacting to the Supreme Court ruling start regulating oral abortifacients, she added. Specifically, this will have a significant impact on patients with rheumatic disease.
Texas pharmacies target two drugs
MTX denials have caught the attention of health care organizations. “Uncertainty in financial and criminal liability for health care professionals in certain state laws and regulations are possibly compromising continuity of care and access [to] medications proven to be safe and effective by the Food and Drug Administration for these indications,” warned the American Pharmacists Association (APhA) in a statement to this news organization.
The APhA said that it was monitoring this situation to assess the effect on patients and pharmacists.
The Arthritis Foundation was made aware of challenges from patients in accessing their MTX prescription for managing their arthritis and shared a statement on the Foundation’s website.
In Texas, pharmacists can refuse to fill scripts for misoprostol and MTX, a combination used for medical abortions. According to the foundation, “Already there are reports that people in Texas who miscarry or take methotrexate for arthritis [are] having trouble getting their prescriptions filled.”
MTX, approved by the FDA in 1985, “is the absolute cornerstone of rheumatoid arthritis. We cannot deny our patients this incredibly valuable drug,” said John Reveille, MD, vice-chair for the department of medicine at the University of Texas McGovern School of Medicine and a member of the Arthritis Foundation expert panel, in an interview.
“While it’s true that methotrexate can be lethal to the fetus, misoprostol is much more likely to cause a spontaneous abortion, and the combination is especially effective,” he said.
“If you look at Cochrane clinical studies, the dose of misoprostol contained in certain combinations with NSAIDs [nonsteroidal anti-inflammatory drugs] can induce spontaneous abortions. It’s surprising that pharmacists are targeting methotrexate, an essential drug in arthritis treatment, when there are medications available that do not have this benefit that can by themselves cause loss of the fetus, such as mifepristone,” added Dr. Reveille.
The Dobbs ruling could also affect the ability of oncologists to provide lifesaving cancer care, according to Jason Westin, MD, an oncologist at the University of Texas MD Anderson Cancer Center in the department of lymphoma and myeloma.
“We have heard of medications with multiple indications, such as methotrexate, not being dispensed by pharmacies due to confusion regarding the intended use and potential consequences for the health care team,” he said in an interview.
Conflicting laws pose challenges for physicians
In North Dakota, inconsistencies in several laws are making it difficult for physicians and pharmacists to make decisions. “Lots of confusion can result when people pass laws against abortion. There’s sometimes no insight into the ramifications of those laws,” said Dr. Miller.
North Dakota approved a trigger law several years ago that makes abortion illegal 30 days after an overturning of Roe. However, another law that regulates abortion conflicts with the trigger law. “Some of the language will need clarification in the next legislative session,” he said.
APhA and other pharmacy associations strongly favor not interfering with the doctor- or pharmacist-patient relationship. The law needs to defer to appropriate care between doctor and patient, said Dr. Miller. State pharmacy associations in North Dakota are working with legislatures to clarify any exceptions in the law, he added.
Arizona lawmakers are trying to reconcile two abortion laws on the books. One, based on an 1864 territorial law, deems abortion illegal. In addition, a newly approved law bans abortions after 15 weeks. The latter will go into effect in September 2022. In both laws, a risk to the mother’s life is the only exception for abortion, said Dr. Young.
Denials aren’t widespread
Not all doctors are seeing MTX denials, but they’re worried about the future. “To date, we have not encountered difficulty in obtaining methotrexate based upon state abortion restrictions but are concerned that this could occur and result in dangerous delays in care,” said Dr. Westin.
Dr. Reveille, who practices rheumatology in Houston, has not yet received any complaints from patients. Things may be different in more rural parts of Texas, where pharmacists could be denying prescriptions based on religious issues, he offered.
It’s a little soon to see what repercussions may result from the Supreme Court ruling and state actions, said Dr. Reveille. “In Texas, we’re a bit ahead of the tidal wave.”
Access problems also haven’t shown up at the university clinic where Dr. Young practices. “In Arizona, it’s unclear if there would be a legal basis to refuse a person methotrexate on the basis that it can be used as an abortifacient,” she said.
Specificity is key in writing Rx scripts
Physicians can make things easier for patients by writing the indication and dose for the drug on the prescription slip. For example, a 10-mg script for MTX is not going to be used for an abortion, said Dr. Miller.
Rheumatologists in Texas have been doing this for some time, even before the Supreme Court ruling, said Fehmida Zahabi, MD, FACR, president of the Society of Texas Association of Rheumatology. For MTX prescriptions in premenopausal women, “patients are told their doctor needs to call the pharmacist. In the small print, we are asked to give a diagnosis to make sure we aren’t using it to terminate pregnancies,” said Dr. Zahabi.
She further noted that if the diagnosis is already indicated on the script, pharmacies generally won’t give patients a hard time.
Patients can also ask their physicians for a letter of medical necessity that confirms a drug’s use for a specific medical condition.
Mail order is another option if a local pharmacy won’t fill a prescription, said Dr. Miller. “This is legal unless a state makes it illegal to send an abortifacient across state lines,” he added.
Many medications used in rheumatic diseases are harmful in pregnancy, and it’s important to routinely discuss pregnancy risk and planning in the rheumatology clinic, said Dr. Young. This should include a thorough discussion and referral for long-acting reversible contraception in most cases, she suggested.
Actions at the federal, state level
President Joe Biden recently signed an executive order prompting federal regulators to protect access to medication abortions, among other steps to safeguard access to reproductive services.
In a statement on Twitter, the American College of Rheumatology (ACR) said that it was “ ... following this issue closely to determine if rheumatology providers and patients are experiencing any widespread difficulty accessing methotrexate or if any initial disruptions are potentially temporary and due to the independent actions of pharmacists trying to figure out what is and isn’t allowed where they practice.”
ACR has assembled a task force of medical and policy experts to determine the best course of action for patients.
The Arthritis Foundation also continues to monitor the situation, encouraging patients to call its hotline, said Steven Schultz, director of state legislative affairs, in an interview.
“We are analyzing how medication abortion could cause confusion on the part of providers or pharmacists dispensing the medication and what this means for specific patients,” said Mr. Schultz. Through a survey, the foundation hopes to get a better idea of what’s going on in the states at a macro level.
This may take some time, as states go through a process of lawsuits, injunctions, or coming into session to do something that may affect access to MTX, said Mr. Schultz.
Being involved in local advocacy is more important than ever, stressed Dr. Young. “Additionally, being plugged into what the ACR and other advocacy groups are doing on the national level is helpful as well to know the status of these medication access issues.”
Rheumatologists have a unique voice in this discussion, she added. “We guide our patients to stability for a safe pregnancy, and even with careful planning, we see patients who become critically ill during pregnancy and require lifesaving treatment, which at times can mean an abortion is necessary.”
Oncologists also advocate for their patients on a regular basis to make sure they have access to the care they need, said Dr. Westin. This situation with Roe is no different, he added. “We will continue to use our unique expertise to advocate for policies that assure access to high-quality, evidence-based care – and to help our patients overcome barriers that may interfere.”
Dr. Reveille participated on an advisory board with Eli Lilly in October 2021.
A version of this article first appeared on Medscape.com.
.
The Court’s 5-4 decision in Dobbs v. Jackson Women’s Health Organization, which halted abortion procedures across the country, also appears to be affecting certain drug regimens. Reports have emerged that pharmacies are denying access to methotrexate (MTX), a drug often used in patients with arthritis or cancer, as well as psoriasis and other skin diseases. In very high doses, MTX it is used to terminate an ectopic pregnancy after miscarriage. The drug can also lead to birth defects.
“It’s happening all over,” Donald Miller, PharmD, professor of pharmacy practice at North Dakota State University, Fargo, said in an interview. “Pharmacists are reluctant to dispense it, and rheumatologists are reluctant to prescribe it because they’re afraid of going to jail.”
Becky Schwartz, a patient who takes MTX for lupus, recently tweeted that her physician’s office stopped prescribing the drug because it is considered an abortifacient. “I had care that made my disabled life easier, and [the Supreme Court] took that from me,” Ms. Schwartz wrote.
Prior to the Supreme Court’s ruling, physicians were concerned about the impact an overturning of the 1973 law would have on patient access to MTX and other prescription medications with abortifacient properties. Doctors in general are becoming afraid of prescribing anything that’s a teratogen, said Dr. Miller.
MTX is used far more often for autoimmune disease than as an abortifacient, said rheumatologist Kristen Young, MD, clinical assistant professor at the University of Arizona College of Medicine, Phoenix. It’s a slippery slope if states reacting to the Supreme Court ruling start regulating oral abortifacients, she added. Specifically, this will have a significant impact on patients with rheumatic disease.
Texas pharmacies target two drugs
MTX denials have caught the attention of health care organizations. “Uncertainty in financial and criminal liability for health care professionals in certain state laws and regulations are possibly compromising continuity of care and access [to] medications proven to be safe and effective by the Food and Drug Administration for these indications,” warned the American Pharmacists Association (APhA) in a statement to this news organization.
The APhA said that it was monitoring this situation to assess the effect on patients and pharmacists.
The Arthritis Foundation was made aware of challenges from patients in accessing their MTX prescription for managing their arthritis and shared a statement on the Foundation’s website.
In Texas, pharmacists can refuse to fill scripts for misoprostol and MTX, a combination used for medical abortions. According to the foundation, “Already there are reports that people in Texas who miscarry or take methotrexate for arthritis [are] having trouble getting their prescriptions filled.”
MTX, approved by the FDA in 1985, “is the absolute cornerstone of rheumatoid arthritis. We cannot deny our patients this incredibly valuable drug,” said John Reveille, MD, vice-chair for the department of medicine at the University of Texas McGovern School of Medicine and a member of the Arthritis Foundation expert panel, in an interview.
“While it’s true that methotrexate can be lethal to the fetus, misoprostol is much more likely to cause a spontaneous abortion, and the combination is especially effective,” he said.
“If you look at Cochrane clinical studies, the dose of misoprostol contained in certain combinations with NSAIDs [nonsteroidal anti-inflammatory drugs] can induce spontaneous abortions. It’s surprising that pharmacists are targeting methotrexate, an essential drug in arthritis treatment, when there are medications available that do not have this benefit that can by themselves cause loss of the fetus, such as mifepristone,” added Dr. Reveille.
The Dobbs ruling could also affect the ability of oncologists to provide lifesaving cancer care, according to Jason Westin, MD, an oncologist at the University of Texas MD Anderson Cancer Center in the department of lymphoma and myeloma.
“We have heard of medications with multiple indications, such as methotrexate, not being dispensed by pharmacies due to confusion regarding the intended use and potential consequences for the health care team,” he said in an interview.
Conflicting laws pose challenges for physicians
In North Dakota, inconsistencies in several laws are making it difficult for physicians and pharmacists to make decisions. “Lots of confusion can result when people pass laws against abortion. There’s sometimes no insight into the ramifications of those laws,” said Dr. Miller.
North Dakota approved a trigger law several years ago that makes abortion illegal 30 days after an overturning of Roe. However, another law that regulates abortion conflicts with the trigger law. “Some of the language will need clarification in the next legislative session,” he said.
APhA and other pharmacy associations strongly favor not interfering with the doctor- or pharmacist-patient relationship. The law needs to defer to appropriate care between doctor and patient, said Dr. Miller. State pharmacy associations in North Dakota are working with legislatures to clarify any exceptions in the law, he added.
Arizona lawmakers are trying to reconcile two abortion laws on the books. One, based on an 1864 territorial law, deems abortion illegal. In addition, a newly approved law bans abortions after 15 weeks. The latter will go into effect in September 2022. In both laws, a risk to the mother’s life is the only exception for abortion, said Dr. Young.
Denials aren’t widespread
Not all doctors are seeing MTX denials, but they’re worried about the future. “To date, we have not encountered difficulty in obtaining methotrexate based upon state abortion restrictions but are concerned that this could occur and result in dangerous delays in care,” said Dr. Westin.
Dr. Reveille, who practices rheumatology in Houston, has not yet received any complaints from patients. Things may be different in more rural parts of Texas, where pharmacists could be denying prescriptions based on religious issues, he offered.
It’s a little soon to see what repercussions may result from the Supreme Court ruling and state actions, said Dr. Reveille. “In Texas, we’re a bit ahead of the tidal wave.”
Access problems also haven’t shown up at the university clinic where Dr. Young practices. “In Arizona, it’s unclear if there would be a legal basis to refuse a person methotrexate on the basis that it can be used as an abortifacient,” she said.
Specificity is key in writing Rx scripts
Physicians can make things easier for patients by writing the indication and dose for the drug on the prescription slip. For example, a 10-mg script for MTX is not going to be used for an abortion, said Dr. Miller.
Rheumatologists in Texas have been doing this for some time, even before the Supreme Court ruling, said Fehmida Zahabi, MD, FACR, president of the Society of Texas Association of Rheumatology. For MTX prescriptions in premenopausal women, “patients are told their doctor needs to call the pharmacist. In the small print, we are asked to give a diagnosis to make sure we aren’t using it to terminate pregnancies,” said Dr. Zahabi.
She further noted that if the diagnosis is already indicated on the script, pharmacies generally won’t give patients a hard time.
Patients can also ask their physicians for a letter of medical necessity that confirms a drug’s use for a specific medical condition.
Mail order is another option if a local pharmacy won’t fill a prescription, said Dr. Miller. “This is legal unless a state makes it illegal to send an abortifacient across state lines,” he added.
Many medications used in rheumatic diseases are harmful in pregnancy, and it’s important to routinely discuss pregnancy risk and planning in the rheumatology clinic, said Dr. Young. This should include a thorough discussion and referral for long-acting reversible contraception in most cases, she suggested.
Actions at the federal, state level
President Joe Biden recently signed an executive order prompting federal regulators to protect access to medication abortions, among other steps to safeguard access to reproductive services.
In a statement on Twitter, the American College of Rheumatology (ACR) said that it was “ ... following this issue closely to determine if rheumatology providers and patients are experiencing any widespread difficulty accessing methotrexate or if any initial disruptions are potentially temporary and due to the independent actions of pharmacists trying to figure out what is and isn’t allowed where they practice.”
ACR has assembled a task force of medical and policy experts to determine the best course of action for patients.
The Arthritis Foundation also continues to monitor the situation, encouraging patients to call its hotline, said Steven Schultz, director of state legislative affairs, in an interview.
“We are analyzing how medication abortion could cause confusion on the part of providers or pharmacists dispensing the medication and what this means for specific patients,” said Mr. Schultz. Through a survey, the foundation hopes to get a better idea of what’s going on in the states at a macro level.
This may take some time, as states go through a process of lawsuits, injunctions, or coming into session to do something that may affect access to MTX, said Mr. Schultz.
Being involved in local advocacy is more important than ever, stressed Dr. Young. “Additionally, being plugged into what the ACR and other advocacy groups are doing on the national level is helpful as well to know the status of these medication access issues.”
Rheumatologists have a unique voice in this discussion, she added. “We guide our patients to stability for a safe pregnancy, and even with careful planning, we see patients who become critically ill during pregnancy and require lifesaving treatment, which at times can mean an abortion is necessary.”
Oncologists also advocate for their patients on a regular basis to make sure they have access to the care they need, said Dr. Westin. This situation with Roe is no different, he added. “We will continue to use our unique expertise to advocate for policies that assure access to high-quality, evidence-based care – and to help our patients overcome barriers that may interfere.”
Dr. Reveille participated on an advisory board with Eli Lilly in October 2021.
A version of this article first appeared on Medscape.com.
Abortion debate may affect Rx decisions for pregnant women
Obstetrician Beverly Gray, MD, is already seeing the effects of the Roe v. Wade abortion debate in her North Carolina practice.
The state allows abortion but requires that women get counseling with a qualified health professional 72 hours before the procedure. “Aside from that, we still have patients asking for more efficacious contraceptive methods just in case,” said Dr. Gray, residency director and division director for women’s community and population health and associate professor for obstetrics and gynecology at Duke University, Durham, N.C.
Patients and staff in her clinic have also been approaching her about tubal ligation. “They’re asking about additional birth control methods because they’re concerned about what’s going to happen” with the challenge to the historic Roe v. Wade decision in the Supreme Court and subsequent actions in the states to restrict or ban abortion, she said.
This has implications not just for abortion but for medications known to affect pregnancy. “What I’m really worried about is physicians will be withholding medicine because they’re concerned about teratogenic effects,” said Dr. Gray.
With more states issuing restrictions on abortion, doctors are worried that patients needing certain drugs to maintain their lupus flares, cancer, or other diseases may decide not to take them in the event they accidentally become pregnant. If the drug is known to affect the fetus, the fear is a patient who lives in a state with abortion restrictions will no longer have the option to terminate a pregnancy.
Instead, a scenario may arise in which the patient – and their physician – may opt not to treat at all with an otherwise lifesaving medication, experts told this news organization.
The U.S. landscape on abortion restrictions
A leaked draft of a U.S. Supreme Court opinion on Mississippi’s 15-week abortion ban has sent the medical community into a tailspin. The case, Dobbs v. Jackson Women’s Health Organization, challenges the 1973 Roe v. Wade decision that affirms the constitutional right to abortion. It’s anticipated the high court will decide on the case in June.
Although the upcoming decision is subject to change, the draft indicated the high court would uphold the Mississippi ban. This would essentially overturn the 1973 ruling. An earlier Supreme Court decision allowing a Texas law banning abortion at 6 weeks suggests the court may already be heading in this direction. At the state level, legislatures have been moving on divergent paths – some taking steps to preserve abortion rights, others initiating restrictions.
More than 100 abortion restrictions in 19 states took effect in 2021, according to the Guttmacher Institute, which tracks such metrics. In 2022, “two key themes are anti-abortion policymakers’ continued pursuit of various types of abortion bans and restrictions on medication abortion,” the institute reported.
Forty-six states and the District of Columbia have introduced 2,025 restrictions or proactive measures on sexual and reproductive health and rights so far this year. The latest tally from Guttmacher, updated in late May, revealed that 11 states so far have enacted 42 abortion restrictions. A total of 6 states (Arizona, Florida, Idaho, Kentucky, Oklahoma, and Wyoming) have issued nine bans on abortion.
Comparatively, 11 states have enacted 19 protective abortion measures.
Twenty-two states have introduced 117 restrictions on medication abortions, which account for 54% of U.S. abortions. This includes seven measures that would ban medication abortion outright, according to Guttmacher. Kentucky and South Dakota collectively have enacted 14 restrictions on medication abortion, as well as provisions that ban mailing of abortion pills.
Chilling effect on prescribing
Some physicians anticipate that drugs such as the “morning-after” pill (levonorgestrel) will become less available as restrictions go into effect, since these are medications designed to prevent pregnancy.*
However, the ongoing effort to put a lid on abortion measures has prompted concerns about a trickle-down effect on other medications that are otherwise life-changing or lifesaving to patients but pose a risk to the fetus.
Several drugs are well documented to affect fetal growth and development of the fetus, ranging from mild, transitory effects to severe, permanent birth defects, said Ronald G. Grifka, MD, chief medical officer of University of Michigan Health-West and clinical professor of pediatrics at the University of Michigan Medical School, Ann Arbor. “As new medications are developed, we will need heightened attention to make sure they are safe for the fetus,” he added.
Certain teratogenic medications are associated with a high risk of abortion even though this isn’t their primary use, noted Christina Chambers, PhD, MPH, co-director of the Center for Better Beginnings and associate director with the Altman Clinical & Translational Research Institute at the University of California, San Diego.
“I don’t think anyone would intentionally take these drugs to induce spontaneous abortion. But if the drugs pose a risk for it, I can see how the laws might be stretched” to include them, said Dr. Chambers.
Methotrexate, a medication for autoimmune disorders, has a high risk of spontaneous abortion. So do acne medications such as isotretinoin.
Patients are usually told they’re not supposed to get pregnant on these drugs because there’s a high risk of pregnancy loss and risk of malformations and potential learning problems in the fetus. But many pregnancies aren’t planned, said Dr. Chambers. “Patients may forget about the side effects or think their birth control will protect them. And the next time they refill the medication, they may not hear about the warnings again.”
With a restrictive abortion law or ban in effect, a woman might think: “I won’t take this drug because if there’s any potential that I might get pregnant, I won’t have the option to abort an at-risk pregnancy.” Women and their doctors, for that matter, don’t want to put themselves in this position, said Dr. Chambers.
Rheumatologist Megan Clowse, MD, who prescribes several medications that potentially cause major birth defects and pregnancy loss, worries about the ramifications of these accumulating bans.
“Methotrexate has been a leading drug for us for decades for rheumatoid arthritis. Mycophenolate is a vital drug for lupus,” said Dr. Clowse, associate professor of medicine at Duke University’s division of rheumatology and immunology.
Both methotrexate and mycophenolate pose about a 40% risk of pregnancy loss and significantly increase the risk for birth defects. “I’m definitely concerned that there might be doctors or women who elect not to use those medications in women of reproductive age because of the potential risk for pregnancy and absence of abortion rights,” said Dr. Clowse.
These situations might force women to use contraceptives they don’t want to use, such as hormonal implants or intrauterine devices, she added. Another side effect is that women and their partners may decide to abstain from sex.
The iPLEDGE factor
Some rheumatology drugs like lenalidomide (Revlimid) require a valid negative pregnancy test in a lab every month. Similarly, the iPLEDGE Risk Evaluation and Mitigation Strategy seeks to reduce the teratogenicity of isotretinoin by requiring two types of birth control and regular pregnancy tests by users.
For isotretinoin specifically, abortion restrictions “could lead to increased adherence to pregnancy prevention measures which are already stringent in iPLEDGE. But on the other hand, it could lead to reduced willingness of physicians to prescribe or patients to take the medication,” said Dr. Chambers.
With programs like iPLEDGE in effect, the rate of pregnancies and abortions that occur in dermatology are relatively low, said Jenny Murase, MD, associate clinical professor of dermatology at the University of California, San Francisco.
Nevertheless, as a physician who regularly prescribes medications like isotretinoin in women of childbearing age, “it’s terrifying to me that a woman wouldn’t have the option to terminate the pregnancy if a teratogenic effect from the medication caused a severe birth defect,” said Dr. Murase.
Dermatologists use other teratogenic medications such as thalidomide, mycophenolate mofetil, and methotrexate for chronic dermatologic disease like psoriasis and atopic dermatitis.
The situation is especially tricky for dermatologists since most patients – about 80% – never discuss their pregnancy with their specialist prior to pregnancy initiation. Dr. Murase recalls when a patient with chronic plaque psoriasis on methotrexate in her late 40s became pregnant and had an abortion even before Dr. Murase became aware of the pregnancy.
Because dermatologists routinely prescribe long-term medications for chronic diseases like acne, psoriasis, and atopic dermatitis, it is important to have a conversation regarding the risks and benefits of long-term medication should a pregnancy occur in any woman of childbearing age, she said.
Fewer women in clinical trials?
Abortion restrictions could possibly discourage women of reproductive age to participate in a clinical trial for a new medication, said Dr. Chambers.
A female patient with a chronic disease who’s randomized to receive a new medication may be required to use certain types of birth control because of unknown potential adverse effects the drug may have on the fetus. But in some cases, accidental pregnancies happen.
The participant in the trial may say, “I don’t know enough about the safety of this drug in pregnancy, and I’ve already taken it. I want to terminate the pregnancy,” said Dr. Chambers. Thinking ahead, a woman may decide not to do the trial to avoid the risk of getting pregnant and not having the option to terminate the pregnancy.
This could apply to new drugs such as antiviral treatments, or medications for severe chronic disease that typically have no clinical trial data in pregnancy prior to initial release into the market.
Women may start taking the drug without thinking about getting pregnant, then realize there are no safety data and become concerned about its effects on a future pregnancy.
The question is: Will abortion restrictions have a chilling effect on these new drugs as well? Patients and their doctors may decide not to try it until more data are available. “I can see where abortion restrictions would change the risk or benefit calculation in thinking about what you do or don’t prescribe or take during reproductive age,” said Dr. Chambers.
The upside of restrictions?
If there’s a positive side to these developments with abortion bans, it may encourage women taking new medications or joining clinical trials to think even more carefully about adherence to effective contraception, said Dr. Chambers.
Some methods are more effective than others, she emphasized. “When you have an unplanned pregnancy, it could mean that the method you used wasn’t optimal or you weren’t using it as recommended.” A goal moving forward is to encourage more thoughtful use of highly effective contraceptives, thus reducing the number of unplanned pregnancies, she added.
If patients are taking methotrexate, “the time to think about pregnancy is before getting pregnant so you can switch to a drug that’s compatible with pregnancy,” she said.
This whole thought process regarding pregnancy planning could work toward useful health goals, said Dr. Chambers. “Nobody thinks termination is the preferred method, but planning ahead should involve a discussion of what works best for the patient.”
Patients do have other choices, said Dr. Grifka. “Fortunately, there are many commonly prescribed medications which cross the placenta and have no ill effects on the fetus.”
Talking to patients about choices
Dr. Clowse, who spends a lot of time training rheumatologists, encourages them to have conversations with patients about pregnancy planning. It’s a lot to manage, getting the right drug to a female patient with chronic illness, especially in this current climate of abortion upheaval, she noted.
Her approach is to have an open and honest conversation with patients about their concerns and fears, what the realities are, and what the potential future options are for certain rheumatology drugs in the United States.
Some women who see what’s happening across the country may become so risk averse that they may choose to die rather than take a lifesaving drug that poses certain risks under new restrictions.
“I think that’s tragic,” said Dr. Clowse.
To help their patients, Dr. Gray believes physicians across specialties should better educate themselves about physiology in pregnancy and how to counsel patients on the impact of not taking medications in pregnancy.
In her view, it’s almost coercive to say to a patient, “You really need to have effective contraception if I’m going to give you this lifesaving or quality-of-life-improving medication.”
When confronting such scenarios, Dr. Gray doesn’t think physicians need to change how they counsel patients about contraception. “I don’t think we should be putting pressure on patients to consider other permanent methods just because there’s a lack of abortion options.”
Patients will eventually make those decisions for themselves, she said. “They’re going to want a more efficacious method because they’re worried about not having access to abortion if they get pregnant.”
Dr. Gray reports being a site principal investigator for a phase 3 trial for VeraCept IUD, funded by Sebela Pharmaceuticals. Dr. Clowse reports receiving research funding and doing consulting for GlaxoSmithKline.
*Correction, 6/2/2022: A previous version of this article misstated the intended use of drugs such as the “morning-after” pill (levonorgestrel). They are taken to prevent unintended pregnancy.
A version of this article first appeared on Medscape.com .
Obstetrician Beverly Gray, MD, is already seeing the effects of the Roe v. Wade abortion debate in her North Carolina practice.
The state allows abortion but requires that women get counseling with a qualified health professional 72 hours before the procedure. “Aside from that, we still have patients asking for more efficacious contraceptive methods just in case,” said Dr. Gray, residency director and division director for women’s community and population health and associate professor for obstetrics and gynecology at Duke University, Durham, N.C.
Patients and staff in her clinic have also been approaching her about tubal ligation. “They’re asking about additional birth control methods because they’re concerned about what’s going to happen” with the challenge to the historic Roe v. Wade decision in the Supreme Court and subsequent actions in the states to restrict or ban abortion, she said.
This has implications not just for abortion but for medications known to affect pregnancy. “What I’m really worried about is physicians will be withholding medicine because they’re concerned about teratogenic effects,” said Dr. Gray.
With more states issuing restrictions on abortion, doctors are worried that patients needing certain drugs to maintain their lupus flares, cancer, or other diseases may decide not to take them in the event they accidentally become pregnant. If the drug is known to affect the fetus, the fear is a patient who lives in a state with abortion restrictions will no longer have the option to terminate a pregnancy.
Instead, a scenario may arise in which the patient – and their physician – may opt not to treat at all with an otherwise lifesaving medication, experts told this news organization.
The U.S. landscape on abortion restrictions
A leaked draft of a U.S. Supreme Court opinion on Mississippi’s 15-week abortion ban has sent the medical community into a tailspin. The case, Dobbs v. Jackson Women’s Health Organization, challenges the 1973 Roe v. Wade decision that affirms the constitutional right to abortion. It’s anticipated the high court will decide on the case in June.
Although the upcoming decision is subject to change, the draft indicated the high court would uphold the Mississippi ban. This would essentially overturn the 1973 ruling. An earlier Supreme Court decision allowing a Texas law banning abortion at 6 weeks suggests the court may already be heading in this direction. At the state level, legislatures have been moving on divergent paths – some taking steps to preserve abortion rights, others initiating restrictions.
More than 100 abortion restrictions in 19 states took effect in 2021, according to the Guttmacher Institute, which tracks such metrics. In 2022, “two key themes are anti-abortion policymakers’ continued pursuit of various types of abortion bans and restrictions on medication abortion,” the institute reported.
Forty-six states and the District of Columbia have introduced 2,025 restrictions or proactive measures on sexual and reproductive health and rights so far this year. The latest tally from Guttmacher, updated in late May, revealed that 11 states so far have enacted 42 abortion restrictions. A total of 6 states (Arizona, Florida, Idaho, Kentucky, Oklahoma, and Wyoming) have issued nine bans on abortion.
Comparatively, 11 states have enacted 19 protective abortion measures.
Twenty-two states have introduced 117 restrictions on medication abortions, which account for 54% of U.S. abortions. This includes seven measures that would ban medication abortion outright, according to Guttmacher. Kentucky and South Dakota collectively have enacted 14 restrictions on medication abortion, as well as provisions that ban mailing of abortion pills.
Chilling effect on prescribing
Some physicians anticipate that drugs such as the “morning-after” pill (levonorgestrel) will become less available as restrictions go into effect, since these are medications designed to prevent pregnancy.*
However, the ongoing effort to put a lid on abortion measures has prompted concerns about a trickle-down effect on other medications that are otherwise life-changing or lifesaving to patients but pose a risk to the fetus.
Several drugs are well documented to affect fetal growth and development of the fetus, ranging from mild, transitory effects to severe, permanent birth defects, said Ronald G. Grifka, MD, chief medical officer of University of Michigan Health-West and clinical professor of pediatrics at the University of Michigan Medical School, Ann Arbor. “As new medications are developed, we will need heightened attention to make sure they are safe for the fetus,” he added.
Certain teratogenic medications are associated with a high risk of abortion even though this isn’t their primary use, noted Christina Chambers, PhD, MPH, co-director of the Center for Better Beginnings and associate director with the Altman Clinical & Translational Research Institute at the University of California, San Diego.
“I don’t think anyone would intentionally take these drugs to induce spontaneous abortion. But if the drugs pose a risk for it, I can see how the laws might be stretched” to include them, said Dr. Chambers.
Methotrexate, a medication for autoimmune disorders, has a high risk of spontaneous abortion. So do acne medications such as isotretinoin.
Patients are usually told they’re not supposed to get pregnant on these drugs because there’s a high risk of pregnancy loss and risk of malformations and potential learning problems in the fetus. But many pregnancies aren’t planned, said Dr. Chambers. “Patients may forget about the side effects or think their birth control will protect them. And the next time they refill the medication, they may not hear about the warnings again.”
With a restrictive abortion law or ban in effect, a woman might think: “I won’t take this drug because if there’s any potential that I might get pregnant, I won’t have the option to abort an at-risk pregnancy.” Women and their doctors, for that matter, don’t want to put themselves in this position, said Dr. Chambers.
Rheumatologist Megan Clowse, MD, who prescribes several medications that potentially cause major birth defects and pregnancy loss, worries about the ramifications of these accumulating bans.
“Methotrexate has been a leading drug for us for decades for rheumatoid arthritis. Mycophenolate is a vital drug for lupus,” said Dr. Clowse, associate professor of medicine at Duke University’s division of rheumatology and immunology.
Both methotrexate and mycophenolate pose about a 40% risk of pregnancy loss and significantly increase the risk for birth defects. “I’m definitely concerned that there might be doctors or women who elect not to use those medications in women of reproductive age because of the potential risk for pregnancy and absence of abortion rights,” said Dr. Clowse.
These situations might force women to use contraceptives they don’t want to use, such as hormonal implants or intrauterine devices, she added. Another side effect is that women and their partners may decide to abstain from sex.
The iPLEDGE factor
Some rheumatology drugs like lenalidomide (Revlimid) require a valid negative pregnancy test in a lab every month. Similarly, the iPLEDGE Risk Evaluation and Mitigation Strategy seeks to reduce the teratogenicity of isotretinoin by requiring two types of birth control and regular pregnancy tests by users.
For isotretinoin specifically, abortion restrictions “could lead to increased adherence to pregnancy prevention measures which are already stringent in iPLEDGE. But on the other hand, it could lead to reduced willingness of physicians to prescribe or patients to take the medication,” said Dr. Chambers.
With programs like iPLEDGE in effect, the rate of pregnancies and abortions that occur in dermatology are relatively low, said Jenny Murase, MD, associate clinical professor of dermatology at the University of California, San Francisco.
Nevertheless, as a physician who regularly prescribes medications like isotretinoin in women of childbearing age, “it’s terrifying to me that a woman wouldn’t have the option to terminate the pregnancy if a teratogenic effect from the medication caused a severe birth defect,” said Dr. Murase.
Dermatologists use other teratogenic medications such as thalidomide, mycophenolate mofetil, and methotrexate for chronic dermatologic disease like psoriasis and atopic dermatitis.
The situation is especially tricky for dermatologists since most patients – about 80% – never discuss their pregnancy with their specialist prior to pregnancy initiation. Dr. Murase recalls when a patient with chronic plaque psoriasis on methotrexate in her late 40s became pregnant and had an abortion even before Dr. Murase became aware of the pregnancy.
Because dermatologists routinely prescribe long-term medications for chronic diseases like acne, psoriasis, and atopic dermatitis, it is important to have a conversation regarding the risks and benefits of long-term medication should a pregnancy occur in any woman of childbearing age, she said.
Fewer women in clinical trials?
Abortion restrictions could possibly discourage women of reproductive age to participate in a clinical trial for a new medication, said Dr. Chambers.
A female patient with a chronic disease who’s randomized to receive a new medication may be required to use certain types of birth control because of unknown potential adverse effects the drug may have on the fetus. But in some cases, accidental pregnancies happen.
The participant in the trial may say, “I don’t know enough about the safety of this drug in pregnancy, and I’ve already taken it. I want to terminate the pregnancy,” said Dr. Chambers. Thinking ahead, a woman may decide not to do the trial to avoid the risk of getting pregnant and not having the option to terminate the pregnancy.
This could apply to new drugs such as antiviral treatments, or medications for severe chronic disease that typically have no clinical trial data in pregnancy prior to initial release into the market.
Women may start taking the drug without thinking about getting pregnant, then realize there are no safety data and become concerned about its effects on a future pregnancy.
The question is: Will abortion restrictions have a chilling effect on these new drugs as well? Patients and their doctors may decide not to try it until more data are available. “I can see where abortion restrictions would change the risk or benefit calculation in thinking about what you do or don’t prescribe or take during reproductive age,” said Dr. Chambers.
The upside of restrictions?
If there’s a positive side to these developments with abortion bans, it may encourage women taking new medications or joining clinical trials to think even more carefully about adherence to effective contraception, said Dr. Chambers.
Some methods are more effective than others, she emphasized. “When you have an unplanned pregnancy, it could mean that the method you used wasn’t optimal or you weren’t using it as recommended.” A goal moving forward is to encourage more thoughtful use of highly effective contraceptives, thus reducing the number of unplanned pregnancies, she added.
If patients are taking methotrexate, “the time to think about pregnancy is before getting pregnant so you can switch to a drug that’s compatible with pregnancy,” she said.
This whole thought process regarding pregnancy planning could work toward useful health goals, said Dr. Chambers. “Nobody thinks termination is the preferred method, but planning ahead should involve a discussion of what works best for the patient.”
Patients do have other choices, said Dr. Grifka. “Fortunately, there are many commonly prescribed medications which cross the placenta and have no ill effects on the fetus.”
Talking to patients about choices
Dr. Clowse, who spends a lot of time training rheumatologists, encourages them to have conversations with patients about pregnancy planning. It’s a lot to manage, getting the right drug to a female patient with chronic illness, especially in this current climate of abortion upheaval, she noted.
Her approach is to have an open and honest conversation with patients about their concerns and fears, what the realities are, and what the potential future options are for certain rheumatology drugs in the United States.
Some women who see what’s happening across the country may become so risk averse that they may choose to die rather than take a lifesaving drug that poses certain risks under new restrictions.
“I think that’s tragic,” said Dr. Clowse.
To help their patients, Dr. Gray believes physicians across specialties should better educate themselves about physiology in pregnancy and how to counsel patients on the impact of not taking medications in pregnancy.
In her view, it’s almost coercive to say to a patient, “You really need to have effective contraception if I’m going to give you this lifesaving or quality-of-life-improving medication.”
When confronting such scenarios, Dr. Gray doesn’t think physicians need to change how they counsel patients about contraception. “I don’t think we should be putting pressure on patients to consider other permanent methods just because there’s a lack of abortion options.”
Patients will eventually make those decisions for themselves, she said. “They’re going to want a more efficacious method because they’re worried about not having access to abortion if they get pregnant.”
Dr. Gray reports being a site principal investigator for a phase 3 trial for VeraCept IUD, funded by Sebela Pharmaceuticals. Dr. Clowse reports receiving research funding and doing consulting for GlaxoSmithKline.
*Correction, 6/2/2022: A previous version of this article misstated the intended use of drugs such as the “morning-after” pill (levonorgestrel). They are taken to prevent unintended pregnancy.
A version of this article first appeared on Medscape.com .
Obstetrician Beverly Gray, MD, is already seeing the effects of the Roe v. Wade abortion debate in her North Carolina practice.
The state allows abortion but requires that women get counseling with a qualified health professional 72 hours before the procedure. “Aside from that, we still have patients asking for more efficacious contraceptive methods just in case,” said Dr. Gray, residency director and division director for women’s community and population health and associate professor for obstetrics and gynecology at Duke University, Durham, N.C.
Patients and staff in her clinic have also been approaching her about tubal ligation. “They’re asking about additional birth control methods because they’re concerned about what’s going to happen” with the challenge to the historic Roe v. Wade decision in the Supreme Court and subsequent actions in the states to restrict or ban abortion, she said.
This has implications not just for abortion but for medications known to affect pregnancy. “What I’m really worried about is physicians will be withholding medicine because they’re concerned about teratogenic effects,” said Dr. Gray.
With more states issuing restrictions on abortion, doctors are worried that patients needing certain drugs to maintain their lupus flares, cancer, or other diseases may decide not to take them in the event they accidentally become pregnant. If the drug is known to affect the fetus, the fear is a patient who lives in a state with abortion restrictions will no longer have the option to terminate a pregnancy.
Instead, a scenario may arise in which the patient – and their physician – may opt not to treat at all with an otherwise lifesaving medication, experts told this news organization.
The U.S. landscape on abortion restrictions
A leaked draft of a U.S. Supreme Court opinion on Mississippi’s 15-week abortion ban has sent the medical community into a tailspin. The case, Dobbs v. Jackson Women’s Health Organization, challenges the 1973 Roe v. Wade decision that affirms the constitutional right to abortion. It’s anticipated the high court will decide on the case in June.
Although the upcoming decision is subject to change, the draft indicated the high court would uphold the Mississippi ban. This would essentially overturn the 1973 ruling. An earlier Supreme Court decision allowing a Texas law banning abortion at 6 weeks suggests the court may already be heading in this direction. At the state level, legislatures have been moving on divergent paths – some taking steps to preserve abortion rights, others initiating restrictions.
More than 100 abortion restrictions in 19 states took effect in 2021, according to the Guttmacher Institute, which tracks such metrics. In 2022, “two key themes are anti-abortion policymakers’ continued pursuit of various types of abortion bans and restrictions on medication abortion,” the institute reported.
Forty-six states and the District of Columbia have introduced 2,025 restrictions or proactive measures on sexual and reproductive health and rights so far this year. The latest tally from Guttmacher, updated in late May, revealed that 11 states so far have enacted 42 abortion restrictions. A total of 6 states (Arizona, Florida, Idaho, Kentucky, Oklahoma, and Wyoming) have issued nine bans on abortion.
Comparatively, 11 states have enacted 19 protective abortion measures.
Twenty-two states have introduced 117 restrictions on medication abortions, which account for 54% of U.S. abortions. This includes seven measures that would ban medication abortion outright, according to Guttmacher. Kentucky and South Dakota collectively have enacted 14 restrictions on medication abortion, as well as provisions that ban mailing of abortion pills.
Chilling effect on prescribing
Some physicians anticipate that drugs such as the “morning-after” pill (levonorgestrel) will become less available as restrictions go into effect, since these are medications designed to prevent pregnancy.*
However, the ongoing effort to put a lid on abortion measures has prompted concerns about a trickle-down effect on other medications that are otherwise life-changing or lifesaving to patients but pose a risk to the fetus.
Several drugs are well documented to affect fetal growth and development of the fetus, ranging from mild, transitory effects to severe, permanent birth defects, said Ronald G. Grifka, MD, chief medical officer of University of Michigan Health-West and clinical professor of pediatrics at the University of Michigan Medical School, Ann Arbor. “As new medications are developed, we will need heightened attention to make sure they are safe for the fetus,” he added.
Certain teratogenic medications are associated with a high risk of abortion even though this isn’t their primary use, noted Christina Chambers, PhD, MPH, co-director of the Center for Better Beginnings and associate director with the Altman Clinical & Translational Research Institute at the University of California, San Diego.
“I don’t think anyone would intentionally take these drugs to induce spontaneous abortion. But if the drugs pose a risk for it, I can see how the laws might be stretched” to include them, said Dr. Chambers.
Methotrexate, a medication for autoimmune disorders, has a high risk of spontaneous abortion. So do acne medications such as isotretinoin.
Patients are usually told they’re not supposed to get pregnant on these drugs because there’s a high risk of pregnancy loss and risk of malformations and potential learning problems in the fetus. But many pregnancies aren’t planned, said Dr. Chambers. “Patients may forget about the side effects or think their birth control will protect them. And the next time they refill the medication, they may not hear about the warnings again.”
With a restrictive abortion law or ban in effect, a woman might think: “I won’t take this drug because if there’s any potential that I might get pregnant, I won’t have the option to abort an at-risk pregnancy.” Women and their doctors, for that matter, don’t want to put themselves in this position, said Dr. Chambers.
Rheumatologist Megan Clowse, MD, who prescribes several medications that potentially cause major birth defects and pregnancy loss, worries about the ramifications of these accumulating bans.
“Methotrexate has been a leading drug for us for decades for rheumatoid arthritis. Mycophenolate is a vital drug for lupus,” said Dr. Clowse, associate professor of medicine at Duke University’s division of rheumatology and immunology.
Both methotrexate and mycophenolate pose about a 40% risk of pregnancy loss and significantly increase the risk for birth defects. “I’m definitely concerned that there might be doctors or women who elect not to use those medications in women of reproductive age because of the potential risk for pregnancy and absence of abortion rights,” said Dr. Clowse.
These situations might force women to use contraceptives they don’t want to use, such as hormonal implants or intrauterine devices, she added. Another side effect is that women and their partners may decide to abstain from sex.
The iPLEDGE factor
Some rheumatology drugs like lenalidomide (Revlimid) require a valid negative pregnancy test in a lab every month. Similarly, the iPLEDGE Risk Evaluation and Mitigation Strategy seeks to reduce the teratogenicity of isotretinoin by requiring two types of birth control and regular pregnancy tests by users.
For isotretinoin specifically, abortion restrictions “could lead to increased adherence to pregnancy prevention measures which are already stringent in iPLEDGE. But on the other hand, it could lead to reduced willingness of physicians to prescribe or patients to take the medication,” said Dr. Chambers.
With programs like iPLEDGE in effect, the rate of pregnancies and abortions that occur in dermatology are relatively low, said Jenny Murase, MD, associate clinical professor of dermatology at the University of California, San Francisco.
Nevertheless, as a physician who regularly prescribes medications like isotretinoin in women of childbearing age, “it’s terrifying to me that a woman wouldn’t have the option to terminate the pregnancy if a teratogenic effect from the medication caused a severe birth defect,” said Dr. Murase.
Dermatologists use other teratogenic medications such as thalidomide, mycophenolate mofetil, and methotrexate for chronic dermatologic disease like psoriasis and atopic dermatitis.
The situation is especially tricky for dermatologists since most patients – about 80% – never discuss their pregnancy with their specialist prior to pregnancy initiation. Dr. Murase recalls when a patient with chronic plaque psoriasis on methotrexate in her late 40s became pregnant and had an abortion even before Dr. Murase became aware of the pregnancy.
Because dermatologists routinely prescribe long-term medications for chronic diseases like acne, psoriasis, and atopic dermatitis, it is important to have a conversation regarding the risks and benefits of long-term medication should a pregnancy occur in any woman of childbearing age, she said.
Fewer women in clinical trials?
Abortion restrictions could possibly discourage women of reproductive age to participate in a clinical trial for a new medication, said Dr. Chambers.
A female patient with a chronic disease who’s randomized to receive a new medication may be required to use certain types of birth control because of unknown potential adverse effects the drug may have on the fetus. But in some cases, accidental pregnancies happen.
The participant in the trial may say, “I don’t know enough about the safety of this drug in pregnancy, and I’ve already taken it. I want to terminate the pregnancy,” said Dr. Chambers. Thinking ahead, a woman may decide not to do the trial to avoid the risk of getting pregnant and not having the option to terminate the pregnancy.
This could apply to new drugs such as antiviral treatments, or medications for severe chronic disease that typically have no clinical trial data in pregnancy prior to initial release into the market.
Women may start taking the drug without thinking about getting pregnant, then realize there are no safety data and become concerned about its effects on a future pregnancy.
The question is: Will abortion restrictions have a chilling effect on these new drugs as well? Patients and their doctors may decide not to try it until more data are available. “I can see where abortion restrictions would change the risk or benefit calculation in thinking about what you do or don’t prescribe or take during reproductive age,” said Dr. Chambers.
The upside of restrictions?
If there’s a positive side to these developments with abortion bans, it may encourage women taking new medications or joining clinical trials to think even more carefully about adherence to effective contraception, said Dr. Chambers.
Some methods are more effective than others, she emphasized. “When you have an unplanned pregnancy, it could mean that the method you used wasn’t optimal or you weren’t using it as recommended.” A goal moving forward is to encourage more thoughtful use of highly effective contraceptives, thus reducing the number of unplanned pregnancies, she added.
If patients are taking methotrexate, “the time to think about pregnancy is before getting pregnant so you can switch to a drug that’s compatible with pregnancy,” she said.
This whole thought process regarding pregnancy planning could work toward useful health goals, said Dr. Chambers. “Nobody thinks termination is the preferred method, but planning ahead should involve a discussion of what works best for the patient.”
Patients do have other choices, said Dr. Grifka. “Fortunately, there are many commonly prescribed medications which cross the placenta and have no ill effects on the fetus.”
Talking to patients about choices
Dr. Clowse, who spends a lot of time training rheumatologists, encourages them to have conversations with patients about pregnancy planning. It’s a lot to manage, getting the right drug to a female patient with chronic illness, especially in this current climate of abortion upheaval, she noted.
Her approach is to have an open and honest conversation with patients about their concerns and fears, what the realities are, and what the potential future options are for certain rheumatology drugs in the United States.
Some women who see what’s happening across the country may become so risk averse that they may choose to die rather than take a lifesaving drug that poses certain risks under new restrictions.
“I think that’s tragic,” said Dr. Clowse.
To help their patients, Dr. Gray believes physicians across specialties should better educate themselves about physiology in pregnancy and how to counsel patients on the impact of not taking medications in pregnancy.
In her view, it’s almost coercive to say to a patient, “You really need to have effective contraception if I’m going to give you this lifesaving or quality-of-life-improving medication.”
When confronting such scenarios, Dr. Gray doesn’t think physicians need to change how they counsel patients about contraception. “I don’t think we should be putting pressure on patients to consider other permanent methods just because there’s a lack of abortion options.”
Patients will eventually make those decisions for themselves, she said. “They’re going to want a more efficacious method because they’re worried about not having access to abortion if they get pregnant.”
Dr. Gray reports being a site principal investigator for a phase 3 trial for VeraCept IUD, funded by Sebela Pharmaceuticals. Dr. Clowse reports receiving research funding and doing consulting for GlaxoSmithKline.
*Correction, 6/2/2022: A previous version of this article misstated the intended use of drugs such as the “morning-after” pill (levonorgestrel). They are taken to prevent unintended pregnancy.
A version of this article first appeared on Medscape.com .
Four mental health trajectories in youth: Predicting persistent psychopathology
A study that tracked psychopathology in 13,000 children and adolescents found that
Investigators also found a strong correlation between new incidence of high psychopathology and externalizing problems such as hyperactivity. “It is of paramount importance to identify factors that distinguish those with persisting problems and escalating trajectories so that resources can be appropriately directed,” wrote the authors of the study published online in JAMA Network Open.
Recent studies have shown that concurrent and sequential comorbidity of psychiatric disorders are very common in adult populations, lead author Colm Healy, PhD, a postdoctoral researcher for psychiatry with the University of Medicine and Health Sciences, Ireland, said in an interview.
The speculation is that this occurs in early life when psychiatry symptoms experience high fluidity. “This presents a complex scenario to model, where young people’s mental health appears to shift and change across development. Few investigations to date have had the data available to examine these trajectories over the full range of child development,” said Dr. Healy.
He and his colleagues attempted to map the profiles and trajectories of psychopathology in children and adolescents, using latent profile transition analysis (LPTA), a person-centered method, to assess comorbidity and movement in the various phases of childhood development.
“The idea behind person-centered methods such as LTPA is that it identifies unobserved subgroups of participants who respond similarly to specific variables – in this case responses to a broad measure of psychopathology,” explained Dr. Healy.
The study included 7,507 children from the child sample (ages 3, 5, and 9 years) and 6,039 children from the adolescent sample (ages 9, 13, and 17 or 18 years). Data analysis took place from October 2020 to September 2021.
Dr. Healy and colleagues in a supplementary investigation compared cohorts at age 9 years to look for sex and generational differences.
Four developmental profiles
Researchers identified 4 distinct developmental profies for person-centered psychopathological trajectories: no psychopathology (incidence range, 60%-70%), high psychopathology (incidence range, 3%-5%), externalizing problems (incidence range, 15%-25%), and internalizing problems (incidence range, 7%-12%).
Internalizing problems reflect issues with peers and emotional problems whereas externalizing problems more closely associate with hyperactivity and conduct.
Less than 5% of the youth studied experienced persistent symptoms. However, 48.6% in the child cohort and 44.1% in the adolescent cohort moved into one of the 3 psychopathology profiles (high psychopathology, externalizing, internalizing problems) at some point in development.
The spread of trajectories was more diverse in the child cohort, said Dr. Healy. “Children ebbed and flowed between the different profiles over time with a large proportion falling into one of the psychopathology categories and then switching between these profiles.” Switching was also evident in the adolescent cohort but to a lesser extent, he said.
Externalizing problems link to high psychopathology
Rates of remittance were higher among individuals in both cohorts for internalizing problems, compared with externalizing problems.
It’s possible that for some of these young people, internalizing problems are a reaction to environmental stressors such as bullying,” said Dr. Healy. “When that stress is relieved, the internalizing problems may dissipate.”
In a clinically relevant finding, children with externalizing problems (age 5, 129 [61.3%] and age 9, 95 [74.3%]) were more likely to present with new incidents of high psychopathology. This was also true in the adolescent group (age 13, 129 [91.1%] and age 17, 146 [89.9%]).
This suggests that a proportion of youth with externalizing problems have an escalating trajectory of psychopathology. “Thus, it may be possible to distinguish those with an escalating trajectory from a stable or remitting trajectory. The specific distinguishing factors require further investigation, but it has been observed before that some of those reporting externalizing problems in early life continue to have difficulties into later life,” noted Dr. Healy.
A combination of environmental or biological factors may explain this escalation, which could respond to early intervention, he said.
Overall, few children in the study transitioned directly from no psychopathology to high psychopathology.
Differences between boys, girls
In both cohorts, investigators noticed significant differences between the sexes.
Boys in childhood made up a larger proportion of the three psychopathology profiles. But by late adolescence, girls made up a larger proportion of the internalizing profile whereas boys made up a larger proportion of the externalizing profile. “These differences were in line with our expectations,” said Dr. Healy.
Trajectories also differed among boys and girls. In childhood, girls had a higher percentage of de-escalating trajectories relative to boys. “More girls than boys in the psychopathology profiles switched to a non or less severe profile. In adolescence, differences in trajectories were less obvious, with the exception that girls were more likely than boys to transition to internalizing problems from all of the other profiles at age 17,” said Dr. Healy.
Most young people who experience psychopathology will eventually see an improvement in symptoms, noted Dr. Healy. Next steps are to identify markers that distinguish individuals with persistent trajectories from remitting trajectories at the different phases of development, he said.
Study draws mixed reviews
Clinical psychiatrists not involved in the study had varying reactions to the results.
“This study is notable for its data-driven and powerful illustration of how childhood and adolescence are dynamic periods during which psychiatric symptoms can emerge and evolve,” said Sunny X. Tang, MD, a psychiatrist and an assistant professor at the Institute of Behavioral Science and the Feinstein Institutes for Medical Research, Manhasset, New York.
The clinical call for action is for person-centered mental health screening to be a routine part of pediatric and adolescent primary care or school-based services, noted Dr. Tang.
Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore, did not think the study would have a significant impact on clinical practice.
He noted that Dr. Healy and coauthors found that some children stayed true to type, but many fluctuated between the four profile groups. The finding that fluctuation occurred more frequently in younger children is not surprising “and is consistent with what we know about the ‘moving targets’ that make diagnosing children so difficult,” said Dr. Nestadt.
“It would have been helpful to have identified clinical indicators of likely persistence in psychopathology, but the measure employed here did not allow that. It is also frustrating to not have any information on treatment, such that we cannot know whether the children who shifted to ‘no psychopathology’ did so because of treatment or spontaneously,” he added.
Victor M. Fornari, MD, MS, director of the Division of Child & Adolescent Psychiatry at The Zucker Hillside Hospital and Cohen’s Children’s Medical Center, New York, said the study is an important contribution to understanding the development of psychopathology during childhood.
“Generally, it is felt that nearly one in five youth will meet criteria for at least one psychiatric disorder by the age of 18. It is well known that externalizing disorders like ADHD manifest earlier in childhood and that depression often manifests later in adolescence,” he said.
No disclosures were reported.
A study that tracked psychopathology in 13,000 children and adolescents found that
Investigators also found a strong correlation between new incidence of high psychopathology and externalizing problems such as hyperactivity. “It is of paramount importance to identify factors that distinguish those with persisting problems and escalating trajectories so that resources can be appropriately directed,” wrote the authors of the study published online in JAMA Network Open.
Recent studies have shown that concurrent and sequential comorbidity of psychiatric disorders are very common in adult populations, lead author Colm Healy, PhD, a postdoctoral researcher for psychiatry with the University of Medicine and Health Sciences, Ireland, said in an interview.
The speculation is that this occurs in early life when psychiatry symptoms experience high fluidity. “This presents a complex scenario to model, where young people’s mental health appears to shift and change across development. Few investigations to date have had the data available to examine these trajectories over the full range of child development,” said Dr. Healy.
He and his colleagues attempted to map the profiles and trajectories of psychopathology in children and adolescents, using latent profile transition analysis (LPTA), a person-centered method, to assess comorbidity and movement in the various phases of childhood development.
“The idea behind person-centered methods such as LTPA is that it identifies unobserved subgroups of participants who respond similarly to specific variables – in this case responses to a broad measure of psychopathology,” explained Dr. Healy.
The study included 7,507 children from the child sample (ages 3, 5, and 9 years) and 6,039 children from the adolescent sample (ages 9, 13, and 17 or 18 years). Data analysis took place from October 2020 to September 2021.
Dr. Healy and colleagues in a supplementary investigation compared cohorts at age 9 years to look for sex and generational differences.
Four developmental profiles
Researchers identified 4 distinct developmental profies for person-centered psychopathological trajectories: no psychopathology (incidence range, 60%-70%), high psychopathology (incidence range, 3%-5%), externalizing problems (incidence range, 15%-25%), and internalizing problems (incidence range, 7%-12%).
Internalizing problems reflect issues with peers and emotional problems whereas externalizing problems more closely associate with hyperactivity and conduct.
Less than 5% of the youth studied experienced persistent symptoms. However, 48.6% in the child cohort and 44.1% in the adolescent cohort moved into one of the 3 psychopathology profiles (high psychopathology, externalizing, internalizing problems) at some point in development.
The spread of trajectories was more diverse in the child cohort, said Dr. Healy. “Children ebbed and flowed between the different profiles over time with a large proportion falling into one of the psychopathology categories and then switching between these profiles.” Switching was also evident in the adolescent cohort but to a lesser extent, he said.
Externalizing problems link to high psychopathology
Rates of remittance were higher among individuals in both cohorts for internalizing problems, compared with externalizing problems.
It’s possible that for some of these young people, internalizing problems are a reaction to environmental stressors such as bullying,” said Dr. Healy. “When that stress is relieved, the internalizing problems may dissipate.”
In a clinically relevant finding, children with externalizing problems (age 5, 129 [61.3%] and age 9, 95 [74.3%]) were more likely to present with new incidents of high psychopathology. This was also true in the adolescent group (age 13, 129 [91.1%] and age 17, 146 [89.9%]).
This suggests that a proportion of youth with externalizing problems have an escalating trajectory of psychopathology. “Thus, it may be possible to distinguish those with an escalating trajectory from a stable or remitting trajectory. The specific distinguishing factors require further investigation, but it has been observed before that some of those reporting externalizing problems in early life continue to have difficulties into later life,” noted Dr. Healy.
A combination of environmental or biological factors may explain this escalation, which could respond to early intervention, he said.
Overall, few children in the study transitioned directly from no psychopathology to high psychopathology.
Differences between boys, girls
In both cohorts, investigators noticed significant differences between the sexes.
Boys in childhood made up a larger proportion of the three psychopathology profiles. But by late adolescence, girls made up a larger proportion of the internalizing profile whereas boys made up a larger proportion of the externalizing profile. “These differences were in line with our expectations,” said Dr. Healy.
Trajectories also differed among boys and girls. In childhood, girls had a higher percentage of de-escalating trajectories relative to boys. “More girls than boys in the psychopathology profiles switched to a non or less severe profile. In adolescence, differences in trajectories were less obvious, with the exception that girls were more likely than boys to transition to internalizing problems from all of the other profiles at age 17,” said Dr. Healy.
Most young people who experience psychopathology will eventually see an improvement in symptoms, noted Dr. Healy. Next steps are to identify markers that distinguish individuals with persistent trajectories from remitting trajectories at the different phases of development, he said.
Study draws mixed reviews
Clinical psychiatrists not involved in the study had varying reactions to the results.
“This study is notable for its data-driven and powerful illustration of how childhood and adolescence are dynamic periods during which psychiatric symptoms can emerge and evolve,” said Sunny X. Tang, MD, a psychiatrist and an assistant professor at the Institute of Behavioral Science and the Feinstein Institutes for Medical Research, Manhasset, New York.
The clinical call for action is for person-centered mental health screening to be a routine part of pediatric and adolescent primary care or school-based services, noted Dr. Tang.
Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore, did not think the study would have a significant impact on clinical practice.
He noted that Dr. Healy and coauthors found that some children stayed true to type, but many fluctuated between the four profile groups. The finding that fluctuation occurred more frequently in younger children is not surprising “and is consistent with what we know about the ‘moving targets’ that make diagnosing children so difficult,” said Dr. Nestadt.
“It would have been helpful to have identified clinical indicators of likely persistence in psychopathology, but the measure employed here did not allow that. It is also frustrating to not have any information on treatment, such that we cannot know whether the children who shifted to ‘no psychopathology’ did so because of treatment or spontaneously,” he added.
Victor M. Fornari, MD, MS, director of the Division of Child & Adolescent Psychiatry at The Zucker Hillside Hospital and Cohen’s Children’s Medical Center, New York, said the study is an important contribution to understanding the development of psychopathology during childhood.
“Generally, it is felt that nearly one in five youth will meet criteria for at least one psychiatric disorder by the age of 18. It is well known that externalizing disorders like ADHD manifest earlier in childhood and that depression often manifests later in adolescence,” he said.
No disclosures were reported.
A study that tracked psychopathology in 13,000 children and adolescents found that
Investigators also found a strong correlation between new incidence of high psychopathology and externalizing problems such as hyperactivity. “It is of paramount importance to identify factors that distinguish those with persisting problems and escalating trajectories so that resources can be appropriately directed,” wrote the authors of the study published online in JAMA Network Open.
Recent studies have shown that concurrent and sequential comorbidity of psychiatric disorders are very common in adult populations, lead author Colm Healy, PhD, a postdoctoral researcher for psychiatry with the University of Medicine and Health Sciences, Ireland, said in an interview.
The speculation is that this occurs in early life when psychiatry symptoms experience high fluidity. “This presents a complex scenario to model, where young people’s mental health appears to shift and change across development. Few investigations to date have had the data available to examine these trajectories over the full range of child development,” said Dr. Healy.
He and his colleagues attempted to map the profiles and trajectories of psychopathology in children and adolescents, using latent profile transition analysis (LPTA), a person-centered method, to assess comorbidity and movement in the various phases of childhood development.
“The idea behind person-centered methods such as LTPA is that it identifies unobserved subgroups of participants who respond similarly to specific variables – in this case responses to a broad measure of psychopathology,” explained Dr. Healy.
The study included 7,507 children from the child sample (ages 3, 5, and 9 years) and 6,039 children from the adolescent sample (ages 9, 13, and 17 or 18 years). Data analysis took place from October 2020 to September 2021.
Dr. Healy and colleagues in a supplementary investigation compared cohorts at age 9 years to look for sex and generational differences.
Four developmental profiles
Researchers identified 4 distinct developmental profies for person-centered psychopathological trajectories: no psychopathology (incidence range, 60%-70%), high psychopathology (incidence range, 3%-5%), externalizing problems (incidence range, 15%-25%), and internalizing problems (incidence range, 7%-12%).
Internalizing problems reflect issues with peers and emotional problems whereas externalizing problems more closely associate with hyperactivity and conduct.
Less than 5% of the youth studied experienced persistent symptoms. However, 48.6% in the child cohort and 44.1% in the adolescent cohort moved into one of the 3 psychopathology profiles (high psychopathology, externalizing, internalizing problems) at some point in development.
The spread of trajectories was more diverse in the child cohort, said Dr. Healy. “Children ebbed and flowed between the different profiles over time with a large proportion falling into one of the psychopathology categories and then switching between these profiles.” Switching was also evident in the adolescent cohort but to a lesser extent, he said.
Externalizing problems link to high psychopathology
Rates of remittance were higher among individuals in both cohorts for internalizing problems, compared with externalizing problems.
It’s possible that for some of these young people, internalizing problems are a reaction to environmental stressors such as bullying,” said Dr. Healy. “When that stress is relieved, the internalizing problems may dissipate.”
In a clinically relevant finding, children with externalizing problems (age 5, 129 [61.3%] and age 9, 95 [74.3%]) were more likely to present with new incidents of high psychopathology. This was also true in the adolescent group (age 13, 129 [91.1%] and age 17, 146 [89.9%]).
This suggests that a proportion of youth with externalizing problems have an escalating trajectory of psychopathology. “Thus, it may be possible to distinguish those with an escalating trajectory from a stable or remitting trajectory. The specific distinguishing factors require further investigation, but it has been observed before that some of those reporting externalizing problems in early life continue to have difficulties into later life,” noted Dr. Healy.
A combination of environmental or biological factors may explain this escalation, which could respond to early intervention, he said.
Overall, few children in the study transitioned directly from no psychopathology to high psychopathology.
Differences between boys, girls
In both cohorts, investigators noticed significant differences between the sexes.
Boys in childhood made up a larger proportion of the three psychopathology profiles. But by late adolescence, girls made up a larger proportion of the internalizing profile whereas boys made up a larger proportion of the externalizing profile. “These differences were in line with our expectations,” said Dr. Healy.
Trajectories also differed among boys and girls. In childhood, girls had a higher percentage of de-escalating trajectories relative to boys. “More girls than boys in the psychopathology profiles switched to a non or less severe profile. In adolescence, differences in trajectories were less obvious, with the exception that girls were more likely than boys to transition to internalizing problems from all of the other profiles at age 17,” said Dr. Healy.
Most young people who experience psychopathology will eventually see an improvement in symptoms, noted Dr. Healy. Next steps are to identify markers that distinguish individuals with persistent trajectories from remitting trajectories at the different phases of development, he said.
Study draws mixed reviews
Clinical psychiatrists not involved in the study had varying reactions to the results.
“This study is notable for its data-driven and powerful illustration of how childhood and adolescence are dynamic periods during which psychiatric symptoms can emerge and evolve,” said Sunny X. Tang, MD, a psychiatrist and an assistant professor at the Institute of Behavioral Science and the Feinstein Institutes for Medical Research, Manhasset, New York.
The clinical call for action is for person-centered mental health screening to be a routine part of pediatric and adolescent primary care or school-based services, noted Dr. Tang.
Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore, did not think the study would have a significant impact on clinical practice.
He noted that Dr. Healy and coauthors found that some children stayed true to type, but many fluctuated between the four profile groups. The finding that fluctuation occurred more frequently in younger children is not surprising “and is consistent with what we know about the ‘moving targets’ that make diagnosing children so difficult,” said Dr. Nestadt.
“It would have been helpful to have identified clinical indicators of likely persistence in psychopathology, but the measure employed here did not allow that. It is also frustrating to not have any information on treatment, such that we cannot know whether the children who shifted to ‘no psychopathology’ did so because of treatment or spontaneously,” he added.
Victor M. Fornari, MD, MS, director of the Division of Child & Adolescent Psychiatry at The Zucker Hillside Hospital and Cohen’s Children’s Medical Center, New York, said the study is an important contribution to understanding the development of psychopathology during childhood.
“Generally, it is felt that nearly one in five youth will meet criteria for at least one psychiatric disorder by the age of 18. It is well known that externalizing disorders like ADHD manifest earlier in childhood and that depression often manifests later in adolescence,” he said.
No disclosures were reported.
FROM JAMA NETWORK OPEN
Women in rheumatology: A look back, a look forward
Jean Liew, MD, recalls the long list of women mentors who have guided her career in rheumatology.
It started during her residency, when Jennifer Barton, MD, at Oregon Health & Science University, Portland, exposed her to new ways of conducting clinical research on patient outcomes.
In fellowship, she met Lianne Gensler, MD, a leader in axial spondyloarthritis, at the annual meeting of the American College of Rheumatology. Through Dr. Gensler’s mentorship and sponsorship, she was introduced to Maureen Dubreuil, MD, at Boston University, whose research focuses on pharmacoepidemiologic approaches using large databases.
Dr. Liew currently practices rheumatology under the leadership of Tuhina Neogi, MD, a world-renowned expert in osteoarthritis and gout. “She’s my research mentor,” Dr. Liew, an assistant professor of medicine at Boston University, said in an interview.
Her academic timeline reflects the powerful network and influence of women rheumatologists, who represent half of the adult rheumatology workforce in the United States. “In the research arena, many experts are women and they serve as role models and mentors to many,” Dr. Liew said.
But there’s more work to do, she and others acknowledged.
Rheumatology faces ongoing workforce shortages while struggling with a gender gap that’s closing but not as quickly as many women rheumatologists would like to see.
The gap persists, despite overall gains in the field of medicine, Vaneet Sandhu, MD, a rheumatologist with Loma Linda (Calif.) University, said in an interview. Women have exceeded men as enrollees in medical colleges, reported the Association of American Medical Colleges. And yet, “our colleagues reported last year that, in academic rheumatology, women are less likely to be full or associate professors than men,” she said.
The odds of being a fellowship program director or division director is similar in both males and females. “So, we’ve had some gains, but there’s always room for more,” Dr. Sandhu said.
Too few physicians
The next 10 years forecasts a dearth in American physicians.
AAMC projects a shortage of 124,000 doctors in the United States by 2034. Following on a similar trajectory, the ACR in 2015 anticipated a 25% drop in the supply of rheumatology clinical providers by 2030, with demand exceeding supply by more than 4,100 clinical employees.
The ACR’s workforce study projected that more women would come into rheumatology, noted Marcy Bolster, MD, director of the rheumatology fellowship training program at Massachusetts General Hospital, Boston. Women make up at least 50% of the workforce and 66% of fellows If these numbers hold, “we’ll definitely see an increase in the percent of women in the workforce” moving forward, Dr. Bolster said in an interview.
Women have helped the shortage to a great extent, said Nilanjana Bose, MD, a rheumatologist at Lonestar Rheumatology, Houston.
The work-life balance that rheumatology offers, combined with its focus on the cognitive part of internal medicine, explains why the field has attracted so many women. Rheumatology provides flexible work options. Women “get to teach or do rounds in the hospital or have a private practice where you’re mostly outpatient with some hospital work,” Dr. Bose said in an interview.
With anticipated shortages looming over the next decade, the profession needs to be cognizant of the different demands women face in their careers and how it can accommodate the workforce to meet the needs of its providers and maintain access for patients, Dr. Bolster said.
There are many innovative ways to match the demand for access. One thought is to create shared positions. Instead of employing four full-time physicians and one person part time, have two people who are working part time, Dr. Bolster suggested. “It is also important to not only expand our workforce with advanced practice providers, but to ensure their retention in the rheumatology workforce, to improve access to care for those with rheumatic diseases.”
Increasing the number of residency positions is another step toward addressing the shortage, Dr. Sandhu offered.
Women rheumatologists should make their voices heard by contacting members of Congress to support legislation that advocates for workforce shortage solutions, “in addition to generally supporting women’s rights and growth in the workplace,” she said.
The gender divide continues
Rosalind Ramsey-Goldman, MD, DrPH, remembers being the only woman in a group of five during her fellowship in the mid-1980s. Few women role models existed within the ACR, especially those in academic careers. “Now, most fellowships have more than 50% women, reflecting the number of women going to medical school,” said Dr. Ramsey-Goldman, Gallagher Research Professor in Rheumatology at Northwestern University and Northwestern Medicine, Chicago.
As more women enter the profession, women rheumatologists in academic rheumatology have started to outpace men in recent years. Some research suggests they’ve made headway in gaining leadership spots at institutions.
One recent paper, a cross-sectional national study of more than 6,100 rheumatologists, found that women had similar odds of attaining fellowship program or division director positions as men. As directors of training programs, women in rheumatology “instill this collaborative and growth mindset that encourages learners to self-reflect and work as a team,” Dr. Sandhu said.
Women bring a different perspective to training, and how curriculum works, Dr. Bose said. Studies have shown that women tend to be more empathic. They ask more questions. “That’s not to say men aren’t good. Women just have an inborn ability for connecting,” and this perspective helps to enrich the educational experience for trainees.
Women who lead training programs are also attuned to realities that female trainees confront, such as dealing with the challenges of achieving the best possible education while also raising a family, noted Graciela S. Alarcón, MD, MPH, who holds emeritus positions at the University of Alabama at Birmingham and the Universidad Peruana Cayetano Heredia in Lima, Peru.
“These program directors cultivate the ability to relate to women trainees in a very personal manner, supporting them in their efforts to achieve a balance between their training demands and their family/personal responsibilities,” she said.
Other research suggests the gender gap hasn’t gone away. Women continue to have lower odds of holding a higher-level professorship, receiving a federal grant, or speaking at academic conferences. They are also less likely to serve as first authors on rheumatology guidelines or recommendations.
Some studies suggest that women see fewer patients and earn less than their male counterparts. At peak difference, men can earn up to $100,000+ more than women. “My own impression is that it takes more efforts for women to reach the same level of recognition than men, and although overt discrimination is rare nowadays, subtle discrimination still occurs,” according to Dr. Alarcón.
Over a lifetime, female physicians can expect to earn less than their male counterparts, with clear implications for different retirement income levels, she said.
Fixing a leaky academic pipeline
The reality is the academic pipeline, and especially the physician-scientist pipeline, “continues to be leaky,” Dr. Liew said. “We know that caregivers to young children have larger barriers to surmount in academics and in research, and that there is a gender disparity present.” The toll of academic medicine on early career women who are parents is especially pronounced. While the pandemic has intensified this problem, it was around pre-COVID, she added.
Women who start in academia as academic clinicians or clinician researchers aren’t always able to meet their goals for promotion within the appropriate time frame. This is because of inequities in the system and lack of support related to maternity leave, childcare, and other issues. As a result, they leave academia and go into private practice or industry, Dr. Liew said.
The ACR in its 2015 survey projected that more women would be seeking part-time positions.
The good news is many academic institutions are taking a more equitable view about different career paths, offering equal parental leave to both men and women, Dr. Bolster noted. “It is essential that workforce planning encompasses the changing responsibilities within families and account for more parental leave by both men and women.” If certain projections come true, with 50% of the profession retiring between 2015 and 2030, combined with more men and women working part time, “it is requisite that workforce strategies plan for this.”
When Dr. Ramsey-Goldman was a trainee and junior faculty, there were no formal maternity leave policies.
Now, this benefit is available, she said. In another critical change, the ACR has made childcare services and a lactation room available for young mothers during its annual meeting. “Virtual meetings afford further ways to interact with colleagues,” she added.
Whether women choose to stay in academia or go into clinical practice is a very personal decision. “But it is also fair that, in some programs, training directors and faculty members can encourage trainees toward academia and its fascinating research possibilities,” Dr. Alarcón offered.
Making gains in research
Women are increasingly driving groundbreaking rheumatology research at all levels, Dr. Sandhu said. “And women empower women. Not infrequently, our female leaders, veterans in rheumatology research, seek younger female rheumatologists to help them grow in their niches. This has been one of the most beautiful things of the sisterhood in rheumatology that I have been blessed to be part of.”
In pediatric rheumatology, young female researchers are leading global research efforts. Some standouts include Kate Webb, MD, a pediatric rheumatologist in Cape Town, South Africa, and scientist who has worked on multisystem inflammatory syndrome during the pandemic. Sheila Angeles-Han, MD, who works on uveitis in juvenile idiopathic arthritis, had a role in recent ACR guidelines. Laura Lewandowski, MD, has also contributed to global rheumatology efforts, especially in low- and middle-income countries, Dr. Liew said.
The 2021 ACR annual meeting highlighted the research efforts of women rheumatologists from around the world. A global rheumatology summit at the meeting featured many women voices, including Dzifa Dey, MD, from Ghana, who received the ACR Distinguished International Rheumatology Professional Award. Ashira Blazer, MD, and Irene Blanco, MD, have spearheaded the ACR’s diversity, equity, and inclusion initiatives.
Women researchers have many opportunities to study rheumatologic diseases that disproportionately affect women, Dr. Alarcón said.
Lupus, for example, affects women in a much higher proportion than men (90% vs. 10%). This may be an attractive target for the best and brightest among future women researchers, Dr. Alarcón suggested. “It is a fact that publications related to lupus in leading internal medicine and rheumatology journals often include women either as first or senior authors. In that context, it can be said that several advances in the study of lupus worldwide can be attributed to women.”
This applies to disparities in social determinants of health that account for extremely complex outcomes in lupus among women of color, compared with White women, in addition to the costs associated with the disease and its impact on morbidity, mortality, and quality of life.
Women rheumatologists have advanced the work in reproductive management of rheumatic diseases, including a recent ACR-endorsed publication that provides formal guidance on managing reproductive health in women with rheumatic disease, Dr. Sandhu said. “One thing is clear: Without women, the work on reproductive diseases in rheumatology to date would not likely be where it is.”
Dr. Ramsey-Goldman added that “this critical work will not only set the stage for clinical care of both women and men regarding their reproductive health but will also inform education strategies for trainees and future research activities, and help direct policy regarding access to care, medication development, and costs of treatment.”
Obtaining grant funding to support salaries and researcher endeavors remains a challenge, Dr. Liew said. “It takes working evenings, weekends, and holidays to meet those goals within a set time frame. So you can see why a female faculty member with children might be disadvantaged, compared to a male counterpart without children.”
Competition for grant funding remains fierce as budgets become tighter, she added.
“We will lose a lot more brilliant and compassionate rheumatologists (clinicians, physician-scientists, and scientists alike) if we do not think of ways to make things more equitable or do not acknowledge the privileges that support some to continued career successes and leave others behind,” Dr. Liew said.
Women who choose a research field should seek out mentor and financial support that will allow them enough protected time to balance out research with other clinical activities, such as teaching and patient care, Dr. Alarcón said.
Training directors, mentors, and faculty should prioritize the needs of current and future women researchers, she said. “The guidance provided to young female trainees toward a successful research career is a formidable challenge that may provide, in turn, enormous satisfaction. There are established avenues to seek funding as new investigators.”
Progress in diversity
Rheumatology as a field is attracting more candidates and all races and genders, Dr. Bose said. “I think in the coming years we will see more and more women from minorities being incorporated into the rheumatology workforce.”
Others would like to see further improvements in diversity and attracting women from historically excluded backgrounds. Patients will benefit from rheumatologists who are able to connect with them through shared languages, cultures, and other life experiences, Dr. Liew said. “It is imperative that we work on recruitment, mentorship, and retention in this regard.”
While the representation of women of color is still inadequate, there has been some progress, Dr. Sandhu said. The number of female Hispanic, Latinx, and Black or African American graduates from medical school has seen a steady rise since 2017. And, AAMC has established task forces such as the Women of Color Initiative to identify strategies for furthering the careers of women of color in academic medicine.
“There’s still a lot of room to grow. I am, however, proud to say we will finally have a woman of color as the president of ACR in 2023,” said Dr. Sandhu, referring to Deborah Dyett Desir, MD.
Dr. Desir discussed the importance of diversifying the ACR in a recent interview.
All rheumatologists know that there is a place for them in the ACR, she stressed. “The demographics of our membership should reflect that of our population.”
As growth in diverse representation occurs, so will recruitment, retention, and a greater awareness and distribution of knowledge and means to address implicit biases and microaggressions, Dr. Sandhu said. “We will see a greater quality of health care, where patients may feel more connected to someone they can identify with.”
Looking ahead
Dr. Alarcón expects women to continue to play a major role in rheumatology, not just in research, education, and patient care but in leadership of academic societies and professional organizations.
“Women in rheumatology have come a long way – a piece of history that I have been fortunate to witness from my beginnings in the early 1970s. We have, I think, paved the way for the next generations of leaders in our beloved specialty field.”
Dr. Bolster is a member of the ACR board of directors and board liaison of the ACR Workforce Solutions Committee. Dr. Ramsey-Goldman has been a GlaxoSmithKline consultant for lupus studies, a consultant and site investigator with Exagen Diagnostics for lupus biomarker studies, and a site investigator for Xencor and Horizon Pharma lupus trials. Dr. Sandhu serves on the ACR’s Committee on Rheumatology Training and Workforce Issues.
Related article
Pioneer days of rheumatology: One veteran looks back
Patricia Woo, CBE, FMedSci, FRCP, has seen it all.
As a member of the British Rheumatology Society and fellow of the Royal College of Physicians, she presented the case for and obtained official training approval for pediatric rheumatology in the 1990s. She also set the wheels in motion to form the Paediatric Rheumatology International Trials Organisation and the Paediatric Rheumatology European Society.
Now 74, Dr. Woo remembers the discrimination she faced in the 1970s. “I was told I couldn’t become an investigator or consultant if I were to marry or have children.” Around the same time, she found out a male clinician researcher didn’t want to work with her, not because of her qualifications, but because she was a woman.
That wouldn’t happen now with all the antidiscrimination laws in place, noted Dr. Woo, an emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. Looking at the advances made by women in rheumatology, “there’s a major difference between 3 decades ago and today. If anyone discriminates today, they are called out.”
As the founding president of the Paediatric Rheumatology European Society, Dr. Woo is one of many early trailblazers who weathered many changes and made gains in the profession.
It’s important to recognize the work of Barbara Ansell, MD, the founder of pediatric rheumatology in the Canadian Red Cross Memorial Hospital, said Dr. Woo. Back in the 1960s, this wasn’t even a subspecialty. “Sick kids in general were taken either to pediatricians who didn’t know much about undescribed rheumatological conditions, and rheumatologists who didn’t know or have facilities for pediatric care.”
Dr. Ansell started this work, and Dr. Woo took over when she retired. With her colleagues, she set up a syllabus for pediatric rheumatology to formalize training for all junior doctors. This established a model of multidisciplinary clinical care and research. “Over the years, more women doctors have been attracted to pediatric rheumatology and have done well,” she said.
The rise of female leaders in rheumatology over the past few decades has been exponential, she continued. Women have become presidents of rheumatologic societies. Some established themselves as leaders in specific disciplines.
Carol Black, MD, from the United Kingdom is renowned for her international collaborative work in scleroderma research and clinical care. Patience White, MD in Washington, D.C., started research on the process of transitioning from childhood to adolescent to adult clinical care, a discipline that now has a strong international presence, Dr. Woo said.
The European Alliance of Associations for Rheumatology, which created a task force on gender equity in academic rheumatology, is evolving, she continued. The Academy of Medical Sciences in the United Kingdom also has active gender equality and mentoring programs, including a program to boost the careers of all researchers.
It’s also much easier now for women to become lead authors on papers since many are heads of lab or clinical services, Dr. Woo continued. “I don’t think there’s much discrimination if you’re a good clinician, and/or a good scientist. If women do their work well, they get the appropriate acknowledgment.”
Jean Liew, MD, recalls the long list of women mentors who have guided her career in rheumatology.
It started during her residency, when Jennifer Barton, MD, at Oregon Health & Science University, Portland, exposed her to new ways of conducting clinical research on patient outcomes.
In fellowship, she met Lianne Gensler, MD, a leader in axial spondyloarthritis, at the annual meeting of the American College of Rheumatology. Through Dr. Gensler’s mentorship and sponsorship, she was introduced to Maureen Dubreuil, MD, at Boston University, whose research focuses on pharmacoepidemiologic approaches using large databases.
Dr. Liew currently practices rheumatology under the leadership of Tuhina Neogi, MD, a world-renowned expert in osteoarthritis and gout. “She’s my research mentor,” Dr. Liew, an assistant professor of medicine at Boston University, said in an interview.
Her academic timeline reflects the powerful network and influence of women rheumatologists, who represent half of the adult rheumatology workforce in the United States. “In the research arena, many experts are women and they serve as role models and mentors to many,” Dr. Liew said.
But there’s more work to do, she and others acknowledged.
Rheumatology faces ongoing workforce shortages while struggling with a gender gap that’s closing but not as quickly as many women rheumatologists would like to see.
The gap persists, despite overall gains in the field of medicine, Vaneet Sandhu, MD, a rheumatologist with Loma Linda (Calif.) University, said in an interview. Women have exceeded men as enrollees in medical colleges, reported the Association of American Medical Colleges. And yet, “our colleagues reported last year that, in academic rheumatology, women are less likely to be full or associate professors than men,” she said.
The odds of being a fellowship program director or division director is similar in both males and females. “So, we’ve had some gains, but there’s always room for more,” Dr. Sandhu said.
Too few physicians
The next 10 years forecasts a dearth in American physicians.
AAMC projects a shortage of 124,000 doctors in the United States by 2034. Following on a similar trajectory, the ACR in 2015 anticipated a 25% drop in the supply of rheumatology clinical providers by 2030, with demand exceeding supply by more than 4,100 clinical employees.
The ACR’s workforce study projected that more women would come into rheumatology, noted Marcy Bolster, MD, director of the rheumatology fellowship training program at Massachusetts General Hospital, Boston. Women make up at least 50% of the workforce and 66% of fellows If these numbers hold, “we’ll definitely see an increase in the percent of women in the workforce” moving forward, Dr. Bolster said in an interview.
Women have helped the shortage to a great extent, said Nilanjana Bose, MD, a rheumatologist at Lonestar Rheumatology, Houston.
The work-life balance that rheumatology offers, combined with its focus on the cognitive part of internal medicine, explains why the field has attracted so many women. Rheumatology provides flexible work options. Women “get to teach or do rounds in the hospital or have a private practice where you’re mostly outpatient with some hospital work,” Dr. Bose said in an interview.
With anticipated shortages looming over the next decade, the profession needs to be cognizant of the different demands women face in their careers and how it can accommodate the workforce to meet the needs of its providers and maintain access for patients, Dr. Bolster said.
There are many innovative ways to match the demand for access. One thought is to create shared positions. Instead of employing four full-time physicians and one person part time, have two people who are working part time, Dr. Bolster suggested. “It is also important to not only expand our workforce with advanced practice providers, but to ensure their retention in the rheumatology workforce, to improve access to care for those with rheumatic diseases.”
Increasing the number of residency positions is another step toward addressing the shortage, Dr. Sandhu offered.
Women rheumatologists should make their voices heard by contacting members of Congress to support legislation that advocates for workforce shortage solutions, “in addition to generally supporting women’s rights and growth in the workplace,” she said.
The gender divide continues
Rosalind Ramsey-Goldman, MD, DrPH, remembers being the only woman in a group of five during her fellowship in the mid-1980s. Few women role models existed within the ACR, especially those in academic careers. “Now, most fellowships have more than 50% women, reflecting the number of women going to medical school,” said Dr. Ramsey-Goldman, Gallagher Research Professor in Rheumatology at Northwestern University and Northwestern Medicine, Chicago.
As more women enter the profession, women rheumatologists in academic rheumatology have started to outpace men in recent years. Some research suggests they’ve made headway in gaining leadership spots at institutions.
One recent paper, a cross-sectional national study of more than 6,100 rheumatologists, found that women had similar odds of attaining fellowship program or division director positions as men. As directors of training programs, women in rheumatology “instill this collaborative and growth mindset that encourages learners to self-reflect and work as a team,” Dr. Sandhu said.
Women bring a different perspective to training, and how curriculum works, Dr. Bose said. Studies have shown that women tend to be more empathic. They ask more questions. “That’s not to say men aren’t good. Women just have an inborn ability for connecting,” and this perspective helps to enrich the educational experience for trainees.
Women who lead training programs are also attuned to realities that female trainees confront, such as dealing with the challenges of achieving the best possible education while also raising a family, noted Graciela S. Alarcón, MD, MPH, who holds emeritus positions at the University of Alabama at Birmingham and the Universidad Peruana Cayetano Heredia in Lima, Peru.
“These program directors cultivate the ability to relate to women trainees in a very personal manner, supporting them in their efforts to achieve a balance between their training demands and their family/personal responsibilities,” she said.
Other research suggests the gender gap hasn’t gone away. Women continue to have lower odds of holding a higher-level professorship, receiving a federal grant, or speaking at academic conferences. They are also less likely to serve as first authors on rheumatology guidelines or recommendations.
Some studies suggest that women see fewer patients and earn less than their male counterparts. At peak difference, men can earn up to $100,000+ more than women. “My own impression is that it takes more efforts for women to reach the same level of recognition than men, and although overt discrimination is rare nowadays, subtle discrimination still occurs,” according to Dr. Alarcón.
Over a lifetime, female physicians can expect to earn less than their male counterparts, with clear implications for different retirement income levels, she said.
Fixing a leaky academic pipeline
The reality is the academic pipeline, and especially the physician-scientist pipeline, “continues to be leaky,” Dr. Liew said. “We know that caregivers to young children have larger barriers to surmount in academics and in research, and that there is a gender disparity present.” The toll of academic medicine on early career women who are parents is especially pronounced. While the pandemic has intensified this problem, it was around pre-COVID, she added.
Women who start in academia as academic clinicians or clinician researchers aren’t always able to meet their goals for promotion within the appropriate time frame. This is because of inequities in the system and lack of support related to maternity leave, childcare, and other issues. As a result, they leave academia and go into private practice or industry, Dr. Liew said.
The ACR in its 2015 survey projected that more women would be seeking part-time positions.
The good news is many academic institutions are taking a more equitable view about different career paths, offering equal parental leave to both men and women, Dr. Bolster noted. “It is essential that workforce planning encompasses the changing responsibilities within families and account for more parental leave by both men and women.” If certain projections come true, with 50% of the profession retiring between 2015 and 2030, combined with more men and women working part time, “it is requisite that workforce strategies plan for this.”
When Dr. Ramsey-Goldman was a trainee and junior faculty, there were no formal maternity leave policies.
Now, this benefit is available, she said. In another critical change, the ACR has made childcare services and a lactation room available for young mothers during its annual meeting. “Virtual meetings afford further ways to interact with colleagues,” she added.
Whether women choose to stay in academia or go into clinical practice is a very personal decision. “But it is also fair that, in some programs, training directors and faculty members can encourage trainees toward academia and its fascinating research possibilities,” Dr. Alarcón offered.
Making gains in research
Women are increasingly driving groundbreaking rheumatology research at all levels, Dr. Sandhu said. “And women empower women. Not infrequently, our female leaders, veterans in rheumatology research, seek younger female rheumatologists to help them grow in their niches. This has been one of the most beautiful things of the sisterhood in rheumatology that I have been blessed to be part of.”
In pediatric rheumatology, young female researchers are leading global research efforts. Some standouts include Kate Webb, MD, a pediatric rheumatologist in Cape Town, South Africa, and scientist who has worked on multisystem inflammatory syndrome during the pandemic. Sheila Angeles-Han, MD, who works on uveitis in juvenile idiopathic arthritis, had a role in recent ACR guidelines. Laura Lewandowski, MD, has also contributed to global rheumatology efforts, especially in low- and middle-income countries, Dr. Liew said.
The 2021 ACR annual meeting highlighted the research efforts of women rheumatologists from around the world. A global rheumatology summit at the meeting featured many women voices, including Dzifa Dey, MD, from Ghana, who received the ACR Distinguished International Rheumatology Professional Award. Ashira Blazer, MD, and Irene Blanco, MD, have spearheaded the ACR’s diversity, equity, and inclusion initiatives.
Women researchers have many opportunities to study rheumatologic diseases that disproportionately affect women, Dr. Alarcón said.
Lupus, for example, affects women in a much higher proportion than men (90% vs. 10%). This may be an attractive target for the best and brightest among future women researchers, Dr. Alarcón suggested. “It is a fact that publications related to lupus in leading internal medicine and rheumatology journals often include women either as first or senior authors. In that context, it can be said that several advances in the study of lupus worldwide can be attributed to women.”
This applies to disparities in social determinants of health that account for extremely complex outcomes in lupus among women of color, compared with White women, in addition to the costs associated with the disease and its impact on morbidity, mortality, and quality of life.
Women rheumatologists have advanced the work in reproductive management of rheumatic diseases, including a recent ACR-endorsed publication that provides formal guidance on managing reproductive health in women with rheumatic disease, Dr. Sandhu said. “One thing is clear: Without women, the work on reproductive diseases in rheumatology to date would not likely be where it is.”
Dr. Ramsey-Goldman added that “this critical work will not only set the stage for clinical care of both women and men regarding their reproductive health but will also inform education strategies for trainees and future research activities, and help direct policy regarding access to care, medication development, and costs of treatment.”
Obtaining grant funding to support salaries and researcher endeavors remains a challenge, Dr. Liew said. “It takes working evenings, weekends, and holidays to meet those goals within a set time frame. So you can see why a female faculty member with children might be disadvantaged, compared to a male counterpart without children.”
Competition for grant funding remains fierce as budgets become tighter, she added.
“We will lose a lot more brilliant and compassionate rheumatologists (clinicians, physician-scientists, and scientists alike) if we do not think of ways to make things more equitable or do not acknowledge the privileges that support some to continued career successes and leave others behind,” Dr. Liew said.
Women who choose a research field should seek out mentor and financial support that will allow them enough protected time to balance out research with other clinical activities, such as teaching and patient care, Dr. Alarcón said.
Training directors, mentors, and faculty should prioritize the needs of current and future women researchers, she said. “The guidance provided to young female trainees toward a successful research career is a formidable challenge that may provide, in turn, enormous satisfaction. There are established avenues to seek funding as new investigators.”
Progress in diversity
Rheumatology as a field is attracting more candidates and all races and genders, Dr. Bose said. “I think in the coming years we will see more and more women from minorities being incorporated into the rheumatology workforce.”
Others would like to see further improvements in diversity and attracting women from historically excluded backgrounds. Patients will benefit from rheumatologists who are able to connect with them through shared languages, cultures, and other life experiences, Dr. Liew said. “It is imperative that we work on recruitment, mentorship, and retention in this regard.”
While the representation of women of color is still inadequate, there has been some progress, Dr. Sandhu said. The number of female Hispanic, Latinx, and Black or African American graduates from medical school has seen a steady rise since 2017. And, AAMC has established task forces such as the Women of Color Initiative to identify strategies for furthering the careers of women of color in academic medicine.
“There’s still a lot of room to grow. I am, however, proud to say we will finally have a woman of color as the president of ACR in 2023,” said Dr. Sandhu, referring to Deborah Dyett Desir, MD.
Dr. Desir discussed the importance of diversifying the ACR in a recent interview.
All rheumatologists know that there is a place for them in the ACR, she stressed. “The demographics of our membership should reflect that of our population.”
As growth in diverse representation occurs, so will recruitment, retention, and a greater awareness and distribution of knowledge and means to address implicit biases and microaggressions, Dr. Sandhu said. “We will see a greater quality of health care, where patients may feel more connected to someone they can identify with.”
Looking ahead
Dr. Alarcón expects women to continue to play a major role in rheumatology, not just in research, education, and patient care but in leadership of academic societies and professional organizations.
“Women in rheumatology have come a long way – a piece of history that I have been fortunate to witness from my beginnings in the early 1970s. We have, I think, paved the way for the next generations of leaders in our beloved specialty field.”
Dr. Bolster is a member of the ACR board of directors and board liaison of the ACR Workforce Solutions Committee. Dr. Ramsey-Goldman has been a GlaxoSmithKline consultant for lupus studies, a consultant and site investigator with Exagen Diagnostics for lupus biomarker studies, and a site investigator for Xencor and Horizon Pharma lupus trials. Dr. Sandhu serves on the ACR’s Committee on Rheumatology Training and Workforce Issues.
Related article
Pioneer days of rheumatology: One veteran looks back
Patricia Woo, CBE, FMedSci, FRCP, has seen it all.
As a member of the British Rheumatology Society and fellow of the Royal College of Physicians, she presented the case for and obtained official training approval for pediatric rheumatology in the 1990s. She also set the wheels in motion to form the Paediatric Rheumatology International Trials Organisation and the Paediatric Rheumatology European Society.
Now 74, Dr. Woo remembers the discrimination she faced in the 1970s. “I was told I couldn’t become an investigator or consultant if I were to marry or have children.” Around the same time, she found out a male clinician researcher didn’t want to work with her, not because of her qualifications, but because she was a woman.
That wouldn’t happen now with all the antidiscrimination laws in place, noted Dr. Woo, an emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. Looking at the advances made by women in rheumatology, “there’s a major difference between 3 decades ago and today. If anyone discriminates today, they are called out.”
As the founding president of the Paediatric Rheumatology European Society, Dr. Woo is one of many early trailblazers who weathered many changes and made gains in the profession.
It’s important to recognize the work of Barbara Ansell, MD, the founder of pediatric rheumatology in the Canadian Red Cross Memorial Hospital, said Dr. Woo. Back in the 1960s, this wasn’t even a subspecialty. “Sick kids in general were taken either to pediatricians who didn’t know much about undescribed rheumatological conditions, and rheumatologists who didn’t know or have facilities for pediatric care.”
Dr. Ansell started this work, and Dr. Woo took over when she retired. With her colleagues, she set up a syllabus for pediatric rheumatology to formalize training for all junior doctors. This established a model of multidisciplinary clinical care and research. “Over the years, more women doctors have been attracted to pediatric rheumatology and have done well,” she said.
The rise of female leaders in rheumatology over the past few decades has been exponential, she continued. Women have become presidents of rheumatologic societies. Some established themselves as leaders in specific disciplines.
Carol Black, MD, from the United Kingdom is renowned for her international collaborative work in scleroderma research and clinical care. Patience White, MD in Washington, D.C., started research on the process of transitioning from childhood to adolescent to adult clinical care, a discipline that now has a strong international presence, Dr. Woo said.
The European Alliance of Associations for Rheumatology, which created a task force on gender equity in academic rheumatology, is evolving, she continued. The Academy of Medical Sciences in the United Kingdom also has active gender equality and mentoring programs, including a program to boost the careers of all researchers.
It’s also much easier now for women to become lead authors on papers since many are heads of lab or clinical services, Dr. Woo continued. “I don’t think there’s much discrimination if you’re a good clinician, and/or a good scientist. If women do their work well, they get the appropriate acknowledgment.”
Jean Liew, MD, recalls the long list of women mentors who have guided her career in rheumatology.
It started during her residency, when Jennifer Barton, MD, at Oregon Health & Science University, Portland, exposed her to new ways of conducting clinical research on patient outcomes.
In fellowship, she met Lianne Gensler, MD, a leader in axial spondyloarthritis, at the annual meeting of the American College of Rheumatology. Through Dr. Gensler’s mentorship and sponsorship, she was introduced to Maureen Dubreuil, MD, at Boston University, whose research focuses on pharmacoepidemiologic approaches using large databases.
Dr. Liew currently practices rheumatology under the leadership of Tuhina Neogi, MD, a world-renowned expert in osteoarthritis and gout. “She’s my research mentor,” Dr. Liew, an assistant professor of medicine at Boston University, said in an interview.
Her academic timeline reflects the powerful network and influence of women rheumatologists, who represent half of the adult rheumatology workforce in the United States. “In the research arena, many experts are women and they serve as role models and mentors to many,” Dr. Liew said.
But there’s more work to do, she and others acknowledged.
Rheumatology faces ongoing workforce shortages while struggling with a gender gap that’s closing but not as quickly as many women rheumatologists would like to see.
The gap persists, despite overall gains in the field of medicine, Vaneet Sandhu, MD, a rheumatologist with Loma Linda (Calif.) University, said in an interview. Women have exceeded men as enrollees in medical colleges, reported the Association of American Medical Colleges. And yet, “our colleagues reported last year that, in academic rheumatology, women are less likely to be full or associate professors than men,” she said.
The odds of being a fellowship program director or division director is similar in both males and females. “So, we’ve had some gains, but there’s always room for more,” Dr. Sandhu said.
Too few physicians
The next 10 years forecasts a dearth in American physicians.
AAMC projects a shortage of 124,000 doctors in the United States by 2034. Following on a similar trajectory, the ACR in 2015 anticipated a 25% drop in the supply of rheumatology clinical providers by 2030, with demand exceeding supply by more than 4,100 clinical employees.
The ACR’s workforce study projected that more women would come into rheumatology, noted Marcy Bolster, MD, director of the rheumatology fellowship training program at Massachusetts General Hospital, Boston. Women make up at least 50% of the workforce and 66% of fellows If these numbers hold, “we’ll definitely see an increase in the percent of women in the workforce” moving forward, Dr. Bolster said in an interview.
Women have helped the shortage to a great extent, said Nilanjana Bose, MD, a rheumatologist at Lonestar Rheumatology, Houston.
The work-life balance that rheumatology offers, combined with its focus on the cognitive part of internal medicine, explains why the field has attracted so many women. Rheumatology provides flexible work options. Women “get to teach or do rounds in the hospital or have a private practice where you’re mostly outpatient with some hospital work,” Dr. Bose said in an interview.
With anticipated shortages looming over the next decade, the profession needs to be cognizant of the different demands women face in their careers and how it can accommodate the workforce to meet the needs of its providers and maintain access for patients, Dr. Bolster said.
There are many innovative ways to match the demand for access. One thought is to create shared positions. Instead of employing four full-time physicians and one person part time, have two people who are working part time, Dr. Bolster suggested. “It is also important to not only expand our workforce with advanced practice providers, but to ensure their retention in the rheumatology workforce, to improve access to care for those with rheumatic diseases.”
Increasing the number of residency positions is another step toward addressing the shortage, Dr. Sandhu offered.
Women rheumatologists should make their voices heard by contacting members of Congress to support legislation that advocates for workforce shortage solutions, “in addition to generally supporting women’s rights and growth in the workplace,” she said.
The gender divide continues
Rosalind Ramsey-Goldman, MD, DrPH, remembers being the only woman in a group of five during her fellowship in the mid-1980s. Few women role models existed within the ACR, especially those in academic careers. “Now, most fellowships have more than 50% women, reflecting the number of women going to medical school,” said Dr. Ramsey-Goldman, Gallagher Research Professor in Rheumatology at Northwestern University and Northwestern Medicine, Chicago.
As more women enter the profession, women rheumatologists in academic rheumatology have started to outpace men in recent years. Some research suggests they’ve made headway in gaining leadership spots at institutions.
One recent paper, a cross-sectional national study of more than 6,100 rheumatologists, found that women had similar odds of attaining fellowship program or division director positions as men. As directors of training programs, women in rheumatology “instill this collaborative and growth mindset that encourages learners to self-reflect and work as a team,” Dr. Sandhu said.
Women bring a different perspective to training, and how curriculum works, Dr. Bose said. Studies have shown that women tend to be more empathic. They ask more questions. “That’s not to say men aren’t good. Women just have an inborn ability for connecting,” and this perspective helps to enrich the educational experience for trainees.
Women who lead training programs are also attuned to realities that female trainees confront, such as dealing with the challenges of achieving the best possible education while also raising a family, noted Graciela S. Alarcón, MD, MPH, who holds emeritus positions at the University of Alabama at Birmingham and the Universidad Peruana Cayetano Heredia in Lima, Peru.
“These program directors cultivate the ability to relate to women trainees in a very personal manner, supporting them in their efforts to achieve a balance between their training demands and their family/personal responsibilities,” she said.
Other research suggests the gender gap hasn’t gone away. Women continue to have lower odds of holding a higher-level professorship, receiving a federal grant, or speaking at academic conferences. They are also less likely to serve as first authors on rheumatology guidelines or recommendations.
Some studies suggest that women see fewer patients and earn less than their male counterparts. At peak difference, men can earn up to $100,000+ more than women. “My own impression is that it takes more efforts for women to reach the same level of recognition than men, and although overt discrimination is rare nowadays, subtle discrimination still occurs,” according to Dr. Alarcón.
Over a lifetime, female physicians can expect to earn less than their male counterparts, with clear implications for different retirement income levels, she said.
Fixing a leaky academic pipeline
The reality is the academic pipeline, and especially the physician-scientist pipeline, “continues to be leaky,” Dr. Liew said. “We know that caregivers to young children have larger barriers to surmount in academics and in research, and that there is a gender disparity present.” The toll of academic medicine on early career women who are parents is especially pronounced. While the pandemic has intensified this problem, it was around pre-COVID, she added.
Women who start in academia as academic clinicians or clinician researchers aren’t always able to meet their goals for promotion within the appropriate time frame. This is because of inequities in the system and lack of support related to maternity leave, childcare, and other issues. As a result, they leave academia and go into private practice or industry, Dr. Liew said.
The ACR in its 2015 survey projected that more women would be seeking part-time positions.
The good news is many academic institutions are taking a more equitable view about different career paths, offering equal parental leave to both men and women, Dr. Bolster noted. “It is essential that workforce planning encompasses the changing responsibilities within families and account for more parental leave by both men and women.” If certain projections come true, with 50% of the profession retiring between 2015 and 2030, combined with more men and women working part time, “it is requisite that workforce strategies plan for this.”
When Dr. Ramsey-Goldman was a trainee and junior faculty, there were no formal maternity leave policies.
Now, this benefit is available, she said. In another critical change, the ACR has made childcare services and a lactation room available for young mothers during its annual meeting. “Virtual meetings afford further ways to interact with colleagues,” she added.
Whether women choose to stay in academia or go into clinical practice is a very personal decision. “But it is also fair that, in some programs, training directors and faculty members can encourage trainees toward academia and its fascinating research possibilities,” Dr. Alarcón offered.
Making gains in research
Women are increasingly driving groundbreaking rheumatology research at all levels, Dr. Sandhu said. “And women empower women. Not infrequently, our female leaders, veterans in rheumatology research, seek younger female rheumatologists to help them grow in their niches. This has been one of the most beautiful things of the sisterhood in rheumatology that I have been blessed to be part of.”
In pediatric rheumatology, young female researchers are leading global research efforts. Some standouts include Kate Webb, MD, a pediatric rheumatologist in Cape Town, South Africa, and scientist who has worked on multisystem inflammatory syndrome during the pandemic. Sheila Angeles-Han, MD, who works on uveitis in juvenile idiopathic arthritis, had a role in recent ACR guidelines. Laura Lewandowski, MD, has also contributed to global rheumatology efforts, especially in low- and middle-income countries, Dr. Liew said.
The 2021 ACR annual meeting highlighted the research efforts of women rheumatologists from around the world. A global rheumatology summit at the meeting featured many women voices, including Dzifa Dey, MD, from Ghana, who received the ACR Distinguished International Rheumatology Professional Award. Ashira Blazer, MD, and Irene Blanco, MD, have spearheaded the ACR’s diversity, equity, and inclusion initiatives.
Women researchers have many opportunities to study rheumatologic diseases that disproportionately affect women, Dr. Alarcón said.
Lupus, for example, affects women in a much higher proportion than men (90% vs. 10%). This may be an attractive target for the best and brightest among future women researchers, Dr. Alarcón suggested. “It is a fact that publications related to lupus in leading internal medicine and rheumatology journals often include women either as first or senior authors. In that context, it can be said that several advances in the study of lupus worldwide can be attributed to women.”
This applies to disparities in social determinants of health that account for extremely complex outcomes in lupus among women of color, compared with White women, in addition to the costs associated with the disease and its impact on morbidity, mortality, and quality of life.
Women rheumatologists have advanced the work in reproductive management of rheumatic diseases, including a recent ACR-endorsed publication that provides formal guidance on managing reproductive health in women with rheumatic disease, Dr. Sandhu said. “One thing is clear: Without women, the work on reproductive diseases in rheumatology to date would not likely be where it is.”
Dr. Ramsey-Goldman added that “this critical work will not only set the stage for clinical care of both women and men regarding their reproductive health but will also inform education strategies for trainees and future research activities, and help direct policy regarding access to care, medication development, and costs of treatment.”
Obtaining grant funding to support salaries and researcher endeavors remains a challenge, Dr. Liew said. “It takes working evenings, weekends, and holidays to meet those goals within a set time frame. So you can see why a female faculty member with children might be disadvantaged, compared to a male counterpart without children.”
Competition for grant funding remains fierce as budgets become tighter, she added.
“We will lose a lot more brilliant and compassionate rheumatologists (clinicians, physician-scientists, and scientists alike) if we do not think of ways to make things more equitable or do not acknowledge the privileges that support some to continued career successes and leave others behind,” Dr. Liew said.
Women who choose a research field should seek out mentor and financial support that will allow them enough protected time to balance out research with other clinical activities, such as teaching and patient care, Dr. Alarcón said.
Training directors, mentors, and faculty should prioritize the needs of current and future women researchers, she said. “The guidance provided to young female trainees toward a successful research career is a formidable challenge that may provide, in turn, enormous satisfaction. There are established avenues to seek funding as new investigators.”
Progress in diversity
Rheumatology as a field is attracting more candidates and all races and genders, Dr. Bose said. “I think in the coming years we will see more and more women from minorities being incorporated into the rheumatology workforce.”
Others would like to see further improvements in diversity and attracting women from historically excluded backgrounds. Patients will benefit from rheumatologists who are able to connect with them through shared languages, cultures, and other life experiences, Dr. Liew said. “It is imperative that we work on recruitment, mentorship, and retention in this regard.”
While the representation of women of color is still inadequate, there has been some progress, Dr. Sandhu said. The number of female Hispanic, Latinx, and Black or African American graduates from medical school has seen a steady rise since 2017. And, AAMC has established task forces such as the Women of Color Initiative to identify strategies for furthering the careers of women of color in academic medicine.
“There’s still a lot of room to grow. I am, however, proud to say we will finally have a woman of color as the president of ACR in 2023,” said Dr. Sandhu, referring to Deborah Dyett Desir, MD.
Dr. Desir discussed the importance of diversifying the ACR in a recent interview.
All rheumatologists know that there is a place for them in the ACR, she stressed. “The demographics of our membership should reflect that of our population.”
As growth in diverse representation occurs, so will recruitment, retention, and a greater awareness and distribution of knowledge and means to address implicit biases and microaggressions, Dr. Sandhu said. “We will see a greater quality of health care, where patients may feel more connected to someone they can identify with.”
Looking ahead
Dr. Alarcón expects women to continue to play a major role in rheumatology, not just in research, education, and patient care but in leadership of academic societies and professional organizations.
“Women in rheumatology have come a long way – a piece of history that I have been fortunate to witness from my beginnings in the early 1970s. We have, I think, paved the way for the next generations of leaders in our beloved specialty field.”
Dr. Bolster is a member of the ACR board of directors and board liaison of the ACR Workforce Solutions Committee. Dr. Ramsey-Goldman has been a GlaxoSmithKline consultant for lupus studies, a consultant and site investigator with Exagen Diagnostics for lupus biomarker studies, and a site investigator for Xencor and Horizon Pharma lupus trials. Dr. Sandhu serves on the ACR’s Committee on Rheumatology Training and Workforce Issues.
Related article
Pioneer days of rheumatology: One veteran looks back
Patricia Woo, CBE, FMedSci, FRCP, has seen it all.
As a member of the British Rheumatology Society and fellow of the Royal College of Physicians, she presented the case for and obtained official training approval for pediatric rheumatology in the 1990s. She also set the wheels in motion to form the Paediatric Rheumatology International Trials Organisation and the Paediatric Rheumatology European Society.
Now 74, Dr. Woo remembers the discrimination she faced in the 1970s. “I was told I couldn’t become an investigator or consultant if I were to marry or have children.” Around the same time, she found out a male clinician researcher didn’t want to work with her, not because of her qualifications, but because she was a woman.
That wouldn’t happen now with all the antidiscrimination laws in place, noted Dr. Woo, an emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. Looking at the advances made by women in rheumatology, “there’s a major difference between 3 decades ago and today. If anyone discriminates today, they are called out.”
As the founding president of the Paediatric Rheumatology European Society, Dr. Woo is one of many early trailblazers who weathered many changes and made gains in the profession.
It’s important to recognize the work of Barbara Ansell, MD, the founder of pediatric rheumatology in the Canadian Red Cross Memorial Hospital, said Dr. Woo. Back in the 1960s, this wasn’t even a subspecialty. “Sick kids in general were taken either to pediatricians who didn’t know much about undescribed rheumatological conditions, and rheumatologists who didn’t know or have facilities for pediatric care.”
Dr. Ansell started this work, and Dr. Woo took over when she retired. With her colleagues, she set up a syllabus for pediatric rheumatology to formalize training for all junior doctors. This established a model of multidisciplinary clinical care and research. “Over the years, more women doctors have been attracted to pediatric rheumatology and have done well,” she said.
The rise of female leaders in rheumatology over the past few decades has been exponential, she continued. Women have become presidents of rheumatologic societies. Some established themselves as leaders in specific disciplines.
Carol Black, MD, from the United Kingdom is renowned for her international collaborative work in scleroderma research and clinical care. Patience White, MD in Washington, D.C., started research on the process of transitioning from childhood to adolescent to adult clinical care, a discipline that now has a strong international presence, Dr. Woo said.
The European Alliance of Associations for Rheumatology, which created a task force on gender equity in academic rheumatology, is evolving, she continued. The Academy of Medical Sciences in the United Kingdom also has active gender equality and mentoring programs, including a program to boost the careers of all researchers.
It’s also much easier now for women to become lead authors on papers since many are heads of lab or clinical services, Dr. Woo continued. “I don’t think there’s much discrimination if you’re a good clinician, and/or a good scientist. If women do their work well, they get the appropriate acknowledgment.”
Combination antidepressant treatment outperforms monotherapy in meta-analysis
Clinicians should consider this approach as a viable first-line treatment for severe depression and for nonresponders, a team of German researchers concluded.
The findings were published online Feb. 16 in JAMA Psychiatry.
Combining antidepressants is often the next step if a patient with acute depression fails to respond to a monotherapy. In a previous meta-analysis, first author Jonathan Henssler, MD, and colleagues reported on the merits of combining monoamine reuptake inhibitors (selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant) and antagonists of presynaptic alpha2-autoreceptors (mianserin, mirtazapine, trazodone).
Studies that followed yielded mixed results. One randomized controlled trial (RCT) showed signs of substantial superiority when antidepressants were combined; another report from Japan only demonstrated a modest effect, said Christopher Baethge, MD, senior author of the meta-analysis, in an interview. Another recent trial showed better efficacy with monotherapy.
“In our view, this diverse field of trials suggested a reassessment. Specifically, we wanted to find out whether certain combinations are effective whereas others are not,” said Dr. Baethge, a professor of psychiatry at the University of Cologne (Germany).
Combing through Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials, the investigators selected RCTs that compared combinations versus monotherapy antidepressants in adult patients with acute depression. The meta-analysis did not include studies on bipolar depression or maintenance therapy. It also didn’t include comorbid medical conditions and concomitant diagnoses of other psychiatric disorders as exclusion criteria.
Separate investigations of combinations using presynaptic alpha2-autoreceptor antagonists or bupropion also took place.
Treatment efficacy measured as standardized mean difference (SMD) between combination and monotherapy was the primary outcome. Other outcomes included the percent of patients in remission after either treatment course or the percentage of patients stopping drug therapy.
Combination treatments yield better outcomes
Among 39 trials and 6,751 patients included in the analysis, 38 of the trials provided data on the primary outcome.
Combination treatments yielded more superior outcomes, compared with monotherapy (SMD, 0.31; 95% confidence interval, 0.19-0.44). Greater efficacy in the combination approach was indicated in 82% of the studies. This finding also held up when the analysis was restricted to low risk of bias trials, applied as a first-line treatment, and among nonresponders.
Potential advantages of presynaptic alpha2-autoreceptors
In the separate analysis, presynaptic alpha2-autoreceptors did a better job than monotherapy as a first-line treatment and when applied to nonresponder populations. In comparison, bupropion combinations did not outperform monotherapy.
It’s possible that in combinations, “alpha2-autoreceptors effectively counteract, through sedation, the restlessness and agitation that many patients find troublesome when taking monoamine-reuptake inhibitors. Similarly, they may help against sexual dysfunction associated with reuptake inhibitors,” Dr. Baethge suggested.
Presynaptic alpha2-autoreceptors might also boost monoaminergic neurotransmission “by interrupting the inhibition feedback loop initiated when reuptake inhibitors increase neurotransmitter concentrations in the synaptic cleft,” he added.
Whether or not bupropion combinations help patients with treatment-resistant depression is inconclusive, noted Dr. Baethge. “More studies will likely help us get a clearer picture. So far, we can only say that we have not enough evidence to positively recommend bupropion combinations to that group of patients.”
Combining treatments did not yield more dropouts or adverse events than monotherapy. “It may thus be a safe treatment alternative when compared with other second-step strategies in treatment-resistant depression, such as augmenting monotherapy with lithium or atypical psychotic,” the investigators concluded.
Looking at this study’s limitations, the multiple clinical trials examined in a meta-analysis often have different designs, definitions of response and control groups, and use different rating scales, noted Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who was not involved in the study.
Some publication bias was found but overall the results kept their integrity across secondary outcomes and subgroup and sensitivity analyses.
Guidance for choosing more effective therapies
The hope is these results will help clinicians choose more promising combinations, such as presynaptic alpha2-autoreceptor antagonists with SSRIs or SNRIs, as opposed to combinations that are less helpful or haven’t gone through an RCT, said Dr. Baethge.
The findings on tolerability may also encourage some clinicians to consider these combinations, especially if they’ve favored less evidence-based approaches such as switching drugs or increasing the dose, he said.
Polypharmacy is often viewed as undesirable or leading to more side effects, noted Dr. Nasrallah. However, “the combination of a reuptake inhibitor plus an alpha2–presynaptic receptor antagonist like mirtazapine, can actually improve tolerability compared to monotherapy antidepressant because their mechanisms of action offset the side effects while increasing efficacy,” he said.
“Finally, although sedation is a side effect of both mirtazapine and trazodone, that can be helpful for patients with difficulty falling asleep, which is common in major depression,” added Dr. Nasrallah.
Dr. Baethge and Dr. Nasrallah had no disclosures. Dr. Henssler received a research grant from the German Federal Ministry of Education and Research.
Clinicians should consider this approach as a viable first-line treatment for severe depression and for nonresponders, a team of German researchers concluded.
The findings were published online Feb. 16 in JAMA Psychiatry.
Combining antidepressants is often the next step if a patient with acute depression fails to respond to a monotherapy. In a previous meta-analysis, first author Jonathan Henssler, MD, and colleagues reported on the merits of combining monoamine reuptake inhibitors (selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant) and antagonists of presynaptic alpha2-autoreceptors (mianserin, mirtazapine, trazodone).
Studies that followed yielded mixed results. One randomized controlled trial (RCT) showed signs of substantial superiority when antidepressants were combined; another report from Japan only demonstrated a modest effect, said Christopher Baethge, MD, senior author of the meta-analysis, in an interview. Another recent trial showed better efficacy with monotherapy.
“In our view, this diverse field of trials suggested a reassessment. Specifically, we wanted to find out whether certain combinations are effective whereas others are not,” said Dr. Baethge, a professor of psychiatry at the University of Cologne (Germany).
Combing through Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials, the investigators selected RCTs that compared combinations versus monotherapy antidepressants in adult patients with acute depression. The meta-analysis did not include studies on bipolar depression or maintenance therapy. It also didn’t include comorbid medical conditions and concomitant diagnoses of other psychiatric disorders as exclusion criteria.
Separate investigations of combinations using presynaptic alpha2-autoreceptor antagonists or bupropion also took place.
Treatment efficacy measured as standardized mean difference (SMD) between combination and monotherapy was the primary outcome. Other outcomes included the percent of patients in remission after either treatment course or the percentage of patients stopping drug therapy.
Combination treatments yield better outcomes
Among 39 trials and 6,751 patients included in the analysis, 38 of the trials provided data on the primary outcome.
Combination treatments yielded more superior outcomes, compared with monotherapy (SMD, 0.31; 95% confidence interval, 0.19-0.44). Greater efficacy in the combination approach was indicated in 82% of the studies. This finding also held up when the analysis was restricted to low risk of bias trials, applied as a first-line treatment, and among nonresponders.
Potential advantages of presynaptic alpha2-autoreceptors
In the separate analysis, presynaptic alpha2-autoreceptors did a better job than monotherapy as a first-line treatment and when applied to nonresponder populations. In comparison, bupropion combinations did not outperform monotherapy.
It’s possible that in combinations, “alpha2-autoreceptors effectively counteract, through sedation, the restlessness and agitation that many patients find troublesome when taking monoamine-reuptake inhibitors. Similarly, they may help against sexual dysfunction associated with reuptake inhibitors,” Dr. Baethge suggested.
Presynaptic alpha2-autoreceptors might also boost monoaminergic neurotransmission “by interrupting the inhibition feedback loop initiated when reuptake inhibitors increase neurotransmitter concentrations in the synaptic cleft,” he added.
Whether or not bupropion combinations help patients with treatment-resistant depression is inconclusive, noted Dr. Baethge. “More studies will likely help us get a clearer picture. So far, we can only say that we have not enough evidence to positively recommend bupropion combinations to that group of patients.”
Combining treatments did not yield more dropouts or adverse events than monotherapy. “It may thus be a safe treatment alternative when compared with other second-step strategies in treatment-resistant depression, such as augmenting monotherapy with lithium or atypical psychotic,” the investigators concluded.
Looking at this study’s limitations, the multiple clinical trials examined in a meta-analysis often have different designs, definitions of response and control groups, and use different rating scales, noted Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who was not involved in the study.
Some publication bias was found but overall the results kept their integrity across secondary outcomes and subgroup and sensitivity analyses.
Guidance for choosing more effective therapies
The hope is these results will help clinicians choose more promising combinations, such as presynaptic alpha2-autoreceptor antagonists with SSRIs or SNRIs, as opposed to combinations that are less helpful or haven’t gone through an RCT, said Dr. Baethge.
The findings on tolerability may also encourage some clinicians to consider these combinations, especially if they’ve favored less evidence-based approaches such as switching drugs or increasing the dose, he said.
Polypharmacy is often viewed as undesirable or leading to more side effects, noted Dr. Nasrallah. However, “the combination of a reuptake inhibitor plus an alpha2–presynaptic receptor antagonist like mirtazapine, can actually improve tolerability compared to monotherapy antidepressant because their mechanisms of action offset the side effects while increasing efficacy,” he said.
“Finally, although sedation is a side effect of both mirtazapine and trazodone, that can be helpful for patients with difficulty falling asleep, which is common in major depression,” added Dr. Nasrallah.
Dr. Baethge and Dr. Nasrallah had no disclosures. Dr. Henssler received a research grant from the German Federal Ministry of Education and Research.
Clinicians should consider this approach as a viable first-line treatment for severe depression and for nonresponders, a team of German researchers concluded.
The findings were published online Feb. 16 in JAMA Psychiatry.
Combining antidepressants is often the next step if a patient with acute depression fails to respond to a monotherapy. In a previous meta-analysis, first author Jonathan Henssler, MD, and colleagues reported on the merits of combining monoamine reuptake inhibitors (selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant) and antagonists of presynaptic alpha2-autoreceptors (mianserin, mirtazapine, trazodone).
Studies that followed yielded mixed results. One randomized controlled trial (RCT) showed signs of substantial superiority when antidepressants were combined; another report from Japan only demonstrated a modest effect, said Christopher Baethge, MD, senior author of the meta-analysis, in an interview. Another recent trial showed better efficacy with monotherapy.
“In our view, this diverse field of trials suggested a reassessment. Specifically, we wanted to find out whether certain combinations are effective whereas others are not,” said Dr. Baethge, a professor of psychiatry at the University of Cologne (Germany).
Combing through Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials, the investigators selected RCTs that compared combinations versus monotherapy antidepressants in adult patients with acute depression. The meta-analysis did not include studies on bipolar depression or maintenance therapy. It also didn’t include comorbid medical conditions and concomitant diagnoses of other psychiatric disorders as exclusion criteria.
Separate investigations of combinations using presynaptic alpha2-autoreceptor antagonists or bupropion also took place.
Treatment efficacy measured as standardized mean difference (SMD) between combination and monotherapy was the primary outcome. Other outcomes included the percent of patients in remission after either treatment course or the percentage of patients stopping drug therapy.
Combination treatments yield better outcomes
Among 39 trials and 6,751 patients included in the analysis, 38 of the trials provided data on the primary outcome.
Combination treatments yielded more superior outcomes, compared with monotherapy (SMD, 0.31; 95% confidence interval, 0.19-0.44). Greater efficacy in the combination approach was indicated in 82% of the studies. This finding also held up when the analysis was restricted to low risk of bias trials, applied as a first-line treatment, and among nonresponders.
Potential advantages of presynaptic alpha2-autoreceptors
In the separate analysis, presynaptic alpha2-autoreceptors did a better job than monotherapy as a first-line treatment and when applied to nonresponder populations. In comparison, bupropion combinations did not outperform monotherapy.
It’s possible that in combinations, “alpha2-autoreceptors effectively counteract, through sedation, the restlessness and agitation that many patients find troublesome when taking monoamine-reuptake inhibitors. Similarly, they may help against sexual dysfunction associated with reuptake inhibitors,” Dr. Baethge suggested.
Presynaptic alpha2-autoreceptors might also boost monoaminergic neurotransmission “by interrupting the inhibition feedback loop initiated when reuptake inhibitors increase neurotransmitter concentrations in the synaptic cleft,” he added.
Whether or not bupropion combinations help patients with treatment-resistant depression is inconclusive, noted Dr. Baethge. “More studies will likely help us get a clearer picture. So far, we can only say that we have not enough evidence to positively recommend bupropion combinations to that group of patients.”
Combining treatments did not yield more dropouts or adverse events than monotherapy. “It may thus be a safe treatment alternative when compared with other second-step strategies in treatment-resistant depression, such as augmenting monotherapy with lithium or atypical psychotic,” the investigators concluded.
Looking at this study’s limitations, the multiple clinical trials examined in a meta-analysis often have different designs, definitions of response and control groups, and use different rating scales, noted Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who was not involved in the study.
Some publication bias was found but overall the results kept their integrity across secondary outcomes and subgroup and sensitivity analyses.
Guidance for choosing more effective therapies
The hope is these results will help clinicians choose more promising combinations, such as presynaptic alpha2-autoreceptor antagonists with SSRIs or SNRIs, as opposed to combinations that are less helpful or haven’t gone through an RCT, said Dr. Baethge.
The findings on tolerability may also encourage some clinicians to consider these combinations, especially if they’ve favored less evidence-based approaches such as switching drugs or increasing the dose, he said.
Polypharmacy is often viewed as undesirable or leading to more side effects, noted Dr. Nasrallah. However, “the combination of a reuptake inhibitor plus an alpha2–presynaptic receptor antagonist like mirtazapine, can actually improve tolerability compared to monotherapy antidepressant because their mechanisms of action offset the side effects while increasing efficacy,” he said.
“Finally, although sedation is a side effect of both mirtazapine and trazodone, that can be helpful for patients with difficulty falling asleep, which is common in major depression,” added Dr. Nasrallah.
Dr. Baethge and Dr. Nasrallah had no disclosures. Dr. Henssler received a research grant from the German Federal Ministry of Education and Research.
FROM JAMA PSYCHIATRY