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Antiepileptic drugs tied to increased Parkinson’s disease risk
, new research suggests.
Drawing on data from the UK Biobank, investigators compared more than 1,400 individuals diagnosed with Parkinson’s disease with matched control persons and found a considerably higher risk of developing Parkinson’s disease among those who had taken AEDs in comparison with those who had not. There was a trend linking a greater number of AED prescriptions and multiple AEDs associated with a greater risk for Parkinson’s disease.
“We observed an association between the most commonly prescribed antiepileptic drugs in the U.K. and Parkinson’s disease using data from UK Biobank,” said senior author Alastair Noyce, PhD, professor of neurology and neuroepidemiology and honorary consultant neurologist, Queen Mary University of London.
“This is the first time that a comprehensive study of the link between AEDs and Parkinson’s disease has been undertaken,” said Dr. Noyce.
He added that the findings have no immediate clinical implications, “but further research is definitely needed, [as] this is an interesting observation made in a research setting.”
The study was published online in JAMA Neurology.
Plausible, but unclear link
Recent observational studies have found a “temporal association” between epilepsy and incident Parkinson’s disease, but the mechanism underlying this association is “unclear,” the authors wrote.
It is “plausible” that AEDs “may account for some or all of the apparent association between epilepsy and Parkinson’s disease” and that movement disorders are potential side effects of AEDs, but the association between AEDs and Parkinson’s disease has “not been well studied,” so it remains “unclear” whether AEDs play a role in the association.
“We have previously reported an association between epilepsy and Parkinson’s disease in several different datasets. Here, we wanted to see if it could be explained by an association with the drugs used to treat epilepsy rather than epilepsy per se,” Dr. Noyce explained.
Are AEDs the culprit?
The researchers used data from the UK Biobank, a longitudinal cohort study with more than 500,000 participants, as well as linked primary care medication data to conduct a nested case-control study to investigate this potential association. Participants ranged in age from 40 to 69 years and were recruited between 2006 and 2010.
The researchers compared 1,433 individuals diagnosed with Parkinson’s disease with 8,598 control persons who were matched in a 6:1 ratio for age, sex, race, ethnicity, and socioeconomic status (median [interquartile range] age, 71 [65-75] years; 60.9% men; 97.5% White).
Of those with Parkinson’s disease, 4.3% had been prescribed an AED prior to the date of their being diagnosed with Parkinson’s disease, compared with 2.5% in the control group; 4.4% had been diagnosed with epilepsy, compared with 1% of the control persons.
The strongest evidence was for the association between lamotrigine, levetiracetam, and sodium valproate and Parkinson’s disease. There was “weaker evidence” for carbamazepine, although all the AEDs were associated with a higher risk of Parkinson’s disease.
The odds of incident Parkinson’s disease were higher among those who were prescribed one or more AEDs and among individuals who were issued a higher number of prescriptions, the authors reported.
It is possible that it is the epilepsy itself that is associated with the risk of Parkinson’s disease, rather than the drugs, and that “likely explains part of the association we are seeing,” said Dr. Noyce.
“The bottom line is that more research into the links between epilepsy – and drugs used to treat epilepsy – and Parkinson’s disease is needed,” he said.
Moreover, “only with time will we work out whether the findings hold any real clinical relevance,” he added.
Alternative explanations
Commenting on the research, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, said, “It has been established in prior research that there is an association between epilepsy and Parkinson’s disease.” The current study “shows that having had a prescription written for one of four antiepileptic medications was associated with subsequently receiving a diagnosis of Parkinson’s disease.”
Although one possible conclusion is that the AEDs themselves increase the risk of developing Parkinson’s disease, “there seem to be other alternative explanations as to why a person who had been prescribed AEDs has an increased risk of receiving a diagnosis of Parkinson’s disease,” said Dr. Gilbert, an associate professor of neurology at Bellevue Hospital Center, New York, who was not involved with the current study.
For example, pre-motor changes in the brain of persons with Parkinson’s disease “may increase the risk of requiring an AED by potentially increasing the risk of having a seizure,” and “changes in the brain caused by the seizures for which AEDs are prescribed may increase the risk of Parkinson’s disease.”
Moreover, psychiatric changes related to Parkinson’s disease may have led to the prescription for AEDs, because at least two of the AEDs are also prescribed for mood stabilization, Dr. Gilbert suggested.
“An unanswered question that the paper acknowledges is, what about people who receive AEDs for reasons other than seizures? Do they also have an increased risk of Parkinson’s disease? This would be an interesting population to focus on because it would remove the link between AEDs and seizure and focus on the association between AEDs and Parkinson’s disease,” Dr. Gilbert said.
She emphasized that people who take AEDs for seizures “should not jump to the conclusion that they must come off these medications so as not to increase their risk of developing Parkinson’s disease.” She noted that having seizures “can be dangerous – injuries can occur during a seizure, and if a seizure can’t be stopped or a number occur in rapid succession, brain injury may result.”
For these reasons, people with “a tendency to have seizures need to protect themselves with AEDs” and “should certainly reach out to their neurologists with any questions,” Dr. Gilbert said.
The Preventive Neurology Unit is funded by Barts Charity. The Apocrita High Performance Cluster facility, supported by Queen Mary University London Research–IT Services, was used for this research. Dr. Noyce has received grants from Barts Charity, Parkinson’s UK, Cure Parkinson’s, the Michael J. Fox Foundation, Innovate UK, Solvemed, and Alchemab and personal fees from AstraZeneca, AbbVie, Zambon, BIAL, uMedeor, Alchemab, Britannia, and Charco Neurotech outside the submitted work. The other authors’ disclosures are listed on the original article. Dr. Gilbert reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
Drawing on data from the UK Biobank, investigators compared more than 1,400 individuals diagnosed with Parkinson’s disease with matched control persons and found a considerably higher risk of developing Parkinson’s disease among those who had taken AEDs in comparison with those who had not. There was a trend linking a greater number of AED prescriptions and multiple AEDs associated with a greater risk for Parkinson’s disease.
“We observed an association between the most commonly prescribed antiepileptic drugs in the U.K. and Parkinson’s disease using data from UK Biobank,” said senior author Alastair Noyce, PhD, professor of neurology and neuroepidemiology and honorary consultant neurologist, Queen Mary University of London.
“This is the first time that a comprehensive study of the link between AEDs and Parkinson’s disease has been undertaken,” said Dr. Noyce.
He added that the findings have no immediate clinical implications, “but further research is definitely needed, [as] this is an interesting observation made in a research setting.”
The study was published online in JAMA Neurology.
Plausible, but unclear link
Recent observational studies have found a “temporal association” between epilepsy and incident Parkinson’s disease, but the mechanism underlying this association is “unclear,” the authors wrote.
It is “plausible” that AEDs “may account for some or all of the apparent association between epilepsy and Parkinson’s disease” and that movement disorders are potential side effects of AEDs, but the association between AEDs and Parkinson’s disease has “not been well studied,” so it remains “unclear” whether AEDs play a role in the association.
“We have previously reported an association between epilepsy and Parkinson’s disease in several different datasets. Here, we wanted to see if it could be explained by an association with the drugs used to treat epilepsy rather than epilepsy per se,” Dr. Noyce explained.
Are AEDs the culprit?
The researchers used data from the UK Biobank, a longitudinal cohort study with more than 500,000 participants, as well as linked primary care medication data to conduct a nested case-control study to investigate this potential association. Participants ranged in age from 40 to 69 years and were recruited between 2006 and 2010.
The researchers compared 1,433 individuals diagnosed with Parkinson’s disease with 8,598 control persons who were matched in a 6:1 ratio for age, sex, race, ethnicity, and socioeconomic status (median [interquartile range] age, 71 [65-75] years; 60.9% men; 97.5% White).
Of those with Parkinson’s disease, 4.3% had been prescribed an AED prior to the date of their being diagnosed with Parkinson’s disease, compared with 2.5% in the control group; 4.4% had been diagnosed with epilepsy, compared with 1% of the control persons.
The strongest evidence was for the association between lamotrigine, levetiracetam, and sodium valproate and Parkinson’s disease. There was “weaker evidence” for carbamazepine, although all the AEDs were associated with a higher risk of Parkinson’s disease.
The odds of incident Parkinson’s disease were higher among those who were prescribed one or more AEDs and among individuals who were issued a higher number of prescriptions, the authors reported.
It is possible that it is the epilepsy itself that is associated with the risk of Parkinson’s disease, rather than the drugs, and that “likely explains part of the association we are seeing,” said Dr. Noyce.
“The bottom line is that more research into the links between epilepsy – and drugs used to treat epilepsy – and Parkinson’s disease is needed,” he said.
Moreover, “only with time will we work out whether the findings hold any real clinical relevance,” he added.
Alternative explanations
Commenting on the research, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, said, “It has been established in prior research that there is an association between epilepsy and Parkinson’s disease.” The current study “shows that having had a prescription written for one of four antiepileptic medications was associated with subsequently receiving a diagnosis of Parkinson’s disease.”
Although one possible conclusion is that the AEDs themselves increase the risk of developing Parkinson’s disease, “there seem to be other alternative explanations as to why a person who had been prescribed AEDs has an increased risk of receiving a diagnosis of Parkinson’s disease,” said Dr. Gilbert, an associate professor of neurology at Bellevue Hospital Center, New York, who was not involved with the current study.
For example, pre-motor changes in the brain of persons with Parkinson’s disease “may increase the risk of requiring an AED by potentially increasing the risk of having a seizure,” and “changes in the brain caused by the seizures for which AEDs are prescribed may increase the risk of Parkinson’s disease.”
Moreover, psychiatric changes related to Parkinson’s disease may have led to the prescription for AEDs, because at least two of the AEDs are also prescribed for mood stabilization, Dr. Gilbert suggested.
“An unanswered question that the paper acknowledges is, what about people who receive AEDs for reasons other than seizures? Do they also have an increased risk of Parkinson’s disease? This would be an interesting population to focus on because it would remove the link between AEDs and seizure and focus on the association between AEDs and Parkinson’s disease,” Dr. Gilbert said.
She emphasized that people who take AEDs for seizures “should not jump to the conclusion that they must come off these medications so as not to increase their risk of developing Parkinson’s disease.” She noted that having seizures “can be dangerous – injuries can occur during a seizure, and if a seizure can’t be stopped or a number occur in rapid succession, brain injury may result.”
For these reasons, people with “a tendency to have seizures need to protect themselves with AEDs” and “should certainly reach out to their neurologists with any questions,” Dr. Gilbert said.
The Preventive Neurology Unit is funded by Barts Charity. The Apocrita High Performance Cluster facility, supported by Queen Mary University London Research–IT Services, was used for this research. Dr. Noyce has received grants from Barts Charity, Parkinson’s UK, Cure Parkinson’s, the Michael J. Fox Foundation, Innovate UK, Solvemed, and Alchemab and personal fees from AstraZeneca, AbbVie, Zambon, BIAL, uMedeor, Alchemab, Britannia, and Charco Neurotech outside the submitted work. The other authors’ disclosures are listed on the original article. Dr. Gilbert reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
Drawing on data from the UK Biobank, investigators compared more than 1,400 individuals diagnosed with Parkinson’s disease with matched control persons and found a considerably higher risk of developing Parkinson’s disease among those who had taken AEDs in comparison with those who had not. There was a trend linking a greater number of AED prescriptions and multiple AEDs associated with a greater risk for Parkinson’s disease.
“We observed an association between the most commonly prescribed antiepileptic drugs in the U.K. and Parkinson’s disease using data from UK Biobank,” said senior author Alastair Noyce, PhD, professor of neurology and neuroepidemiology and honorary consultant neurologist, Queen Mary University of London.
“This is the first time that a comprehensive study of the link between AEDs and Parkinson’s disease has been undertaken,” said Dr. Noyce.
He added that the findings have no immediate clinical implications, “but further research is definitely needed, [as] this is an interesting observation made in a research setting.”
The study was published online in JAMA Neurology.
Plausible, but unclear link
Recent observational studies have found a “temporal association” between epilepsy and incident Parkinson’s disease, but the mechanism underlying this association is “unclear,” the authors wrote.
It is “plausible” that AEDs “may account for some or all of the apparent association between epilepsy and Parkinson’s disease” and that movement disorders are potential side effects of AEDs, but the association between AEDs and Parkinson’s disease has “not been well studied,” so it remains “unclear” whether AEDs play a role in the association.
“We have previously reported an association between epilepsy and Parkinson’s disease in several different datasets. Here, we wanted to see if it could be explained by an association with the drugs used to treat epilepsy rather than epilepsy per se,” Dr. Noyce explained.
Are AEDs the culprit?
The researchers used data from the UK Biobank, a longitudinal cohort study with more than 500,000 participants, as well as linked primary care medication data to conduct a nested case-control study to investigate this potential association. Participants ranged in age from 40 to 69 years and were recruited between 2006 and 2010.
The researchers compared 1,433 individuals diagnosed with Parkinson’s disease with 8,598 control persons who were matched in a 6:1 ratio for age, sex, race, ethnicity, and socioeconomic status (median [interquartile range] age, 71 [65-75] years; 60.9% men; 97.5% White).
Of those with Parkinson’s disease, 4.3% had been prescribed an AED prior to the date of their being diagnosed with Parkinson’s disease, compared with 2.5% in the control group; 4.4% had been diagnosed with epilepsy, compared with 1% of the control persons.
The strongest evidence was for the association between lamotrigine, levetiracetam, and sodium valproate and Parkinson’s disease. There was “weaker evidence” for carbamazepine, although all the AEDs were associated with a higher risk of Parkinson’s disease.
The odds of incident Parkinson’s disease were higher among those who were prescribed one or more AEDs and among individuals who were issued a higher number of prescriptions, the authors reported.
It is possible that it is the epilepsy itself that is associated with the risk of Parkinson’s disease, rather than the drugs, and that “likely explains part of the association we are seeing,” said Dr. Noyce.
“The bottom line is that more research into the links between epilepsy – and drugs used to treat epilepsy – and Parkinson’s disease is needed,” he said.
Moreover, “only with time will we work out whether the findings hold any real clinical relevance,” he added.
Alternative explanations
Commenting on the research, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, said, “It has been established in prior research that there is an association between epilepsy and Parkinson’s disease.” The current study “shows that having had a prescription written for one of four antiepileptic medications was associated with subsequently receiving a diagnosis of Parkinson’s disease.”
Although one possible conclusion is that the AEDs themselves increase the risk of developing Parkinson’s disease, “there seem to be other alternative explanations as to why a person who had been prescribed AEDs has an increased risk of receiving a diagnosis of Parkinson’s disease,” said Dr. Gilbert, an associate professor of neurology at Bellevue Hospital Center, New York, who was not involved with the current study.
For example, pre-motor changes in the brain of persons with Parkinson’s disease “may increase the risk of requiring an AED by potentially increasing the risk of having a seizure,” and “changes in the brain caused by the seizures for which AEDs are prescribed may increase the risk of Parkinson’s disease.”
Moreover, psychiatric changes related to Parkinson’s disease may have led to the prescription for AEDs, because at least two of the AEDs are also prescribed for mood stabilization, Dr. Gilbert suggested.
“An unanswered question that the paper acknowledges is, what about people who receive AEDs for reasons other than seizures? Do they also have an increased risk of Parkinson’s disease? This would be an interesting population to focus on because it would remove the link between AEDs and seizure and focus on the association between AEDs and Parkinson’s disease,” Dr. Gilbert said.
She emphasized that people who take AEDs for seizures “should not jump to the conclusion that they must come off these medications so as not to increase their risk of developing Parkinson’s disease.” She noted that having seizures “can be dangerous – injuries can occur during a seizure, and if a seizure can’t be stopped or a number occur in rapid succession, brain injury may result.”
For these reasons, people with “a tendency to have seizures need to protect themselves with AEDs” and “should certainly reach out to their neurologists with any questions,” Dr. Gilbert said.
The Preventive Neurology Unit is funded by Barts Charity. The Apocrita High Performance Cluster facility, supported by Queen Mary University London Research–IT Services, was used for this research. Dr. Noyce has received grants from Barts Charity, Parkinson’s UK, Cure Parkinson’s, the Michael J. Fox Foundation, Innovate UK, Solvemed, and Alchemab and personal fees from AstraZeneca, AbbVie, Zambon, BIAL, uMedeor, Alchemab, Britannia, and Charco Neurotech outside the submitted work. The other authors’ disclosures are listed on the original article. Dr. Gilbert reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
Dupilumab effective for eosinophilic esophagitis up to 52 weeks
Few side effects, other than injection pain, emerged in the year-long phase 3 trial that convinced the Food and Drug Administration to approve the drug for EoE in May, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.
The FDA approved dupilumab for the treatment of EoE in people 12 years and older who weigh at least 40 kg (about 88 pounds). The study included patients who had failed to benefit from an 8-week course of high-dose proton pump inhibitor (PPI) therapy, and most also hadn’t had relief from topical steroids.
Because dupilumab is a systemic biologic, such patients are the most likely candidates for the medication, Dr. Dellon said.
Dr. Dellon and colleagues published the study results in the New England Journal of Medicine.
A chronic, progressive, type 2 inflammatory disease of the esophagus, EoE can make it difficult to swallow and cause abdominal and chest pain or vomiting. Specialized diets, topical steroids, and PPIs can help manage EoE for many patients, but these therapies don’t always work, diets are difficult to follow, and topical steroids and PPIs can be difficult to take or cause side effects.
A fully human monoclonal antibody developed by Regeneron Pharmaceuticals and Sanofi, dupilumab blocks the shared receptor component for interleukin-4 and interleukin-13, central drivers of type 2 inflammation in EoE. The FDA has approved dupilumab for atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps.
Three-part trial
For the three-part study conducted in Australia, Canada, Europe, and the United States, participants received 300 mg dupilumab by subcutaneous injection.
In part A, investigators randomly assigned 42 patients to weekly doses of dupilumab and 39 to weekly placebo injections for 24 weeks.
In part B, they randomly divided patients into three groups: Eighty received dupilumab weekly; 81 received dupilumab every 2 weeks; and 79 received a placebo weekly, for 24 weeks.
In part C, the intervention and placebo groups from part A received dupilumab weekly for another 28 weeks. For the two intervention groups in part B, treatment remained the same, while the part B placebo group was evenly split to receive dupilumab weekly or every 2 weeks for 28 weeks.
Over half of patients in remission
In part A, 60% of patients receiving weekly dupilumab achieved histologic remission (defined as no more than six eosinophils per high-power field), compared with 5% of patients receiving placebo, a significant difference (P < .001).
In part B, 59% of patients receiving weekly dupilumab, 60% of those receiving biweekly dupilumab, and 6% of those receiving placebo achieved histologic remission. The difference between those receiving weekly dupilumab or placebo was significant (P < .001).
Symptoms improved with weekly dupilumab, as measured via the Dysphagia Symptom Questionnaire score, which can range from 0 to 84, with higher values indicating more frequent or more severe dysphagia. The mean score at baseline was 33.6 in part A and 36.7 in part B. Scores in patients receiving weekly dupilumab decreased by 12.3 in part A and 9.9 in part B (both P < .001). However, among part B patients receiving biweekly dupilumab, the mean score dropped by only 0.5, which was not significant.
Dupilumab reached a higher serum concentration with the weekly than the biweekly regimen, which may explain the improved symptoms with more frequent dosing, Dr. Dellon said.
Only nine patients experienced serious adverse events during the part A or B treatment period (seven who received weekly dupilumab, one who received biweekly dupilumab, and one who received placebo) and just one patient during the part C treatment period who received placebo in part A and weekly dupilumab in part C. None of these events, except one, were related to the regimen, according to investigators.
Patients who received weekly dupilumab in part A and continued to part C maintained similar treatment effects to week 52, Dr. Dellon said. Although the data on part B patients who continued into part C were not included in the published paper, they were similar, he said.
“The people who responded to the first 24 weeks maintain that response for up to 52 weeks, and there was even a gain of response for some measures,” he said.
Patients, on average, also experienced improvements as measured by endoscopic healing, histological severity scores, and even gene expression, Dr. Dellon said.
‘Welcome addition’
Dupilumab is “a welcome addition to what we do,” said Philip Katz, MD, a professor of medicine in the division of gastroenterology at Weill Cornell Medicine in New York. The publication of this “pivotal” trial provides reassurance about its safety and effectiveness for EoE, he added.
“Dupilumab, or Dupixent, is going to be used in my practice for people who are refractory to both PPIs and topical steroids,” Dr. Katz, who was not involved in the research, said in an interview.
However, it will take practice to know how best to use the drug, and its high cost may make some payers reluctant to cover it, Dr. Katz added.
The study was funded by Sanofi and Regeneron. Dr. Dellon has reported financial relationships with multiple pharmaceutical companies, including Regeneron and Sanofi US. Dr. Katz has reported financial relationships with Phantom Pharmaceuticals, AstraZeneca, and Braintree Laboratories.
A version of this article first appeared on Medscape.com.
Few side effects, other than injection pain, emerged in the year-long phase 3 trial that convinced the Food and Drug Administration to approve the drug for EoE in May, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.
The FDA approved dupilumab for the treatment of EoE in people 12 years and older who weigh at least 40 kg (about 88 pounds). The study included patients who had failed to benefit from an 8-week course of high-dose proton pump inhibitor (PPI) therapy, and most also hadn’t had relief from topical steroids.
Because dupilumab is a systemic biologic, such patients are the most likely candidates for the medication, Dr. Dellon said.
Dr. Dellon and colleagues published the study results in the New England Journal of Medicine.
A chronic, progressive, type 2 inflammatory disease of the esophagus, EoE can make it difficult to swallow and cause abdominal and chest pain or vomiting. Specialized diets, topical steroids, and PPIs can help manage EoE for many patients, but these therapies don’t always work, diets are difficult to follow, and topical steroids and PPIs can be difficult to take or cause side effects.
A fully human monoclonal antibody developed by Regeneron Pharmaceuticals and Sanofi, dupilumab blocks the shared receptor component for interleukin-4 and interleukin-13, central drivers of type 2 inflammation in EoE. The FDA has approved dupilumab for atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps.
Three-part trial
For the three-part study conducted in Australia, Canada, Europe, and the United States, participants received 300 mg dupilumab by subcutaneous injection.
In part A, investigators randomly assigned 42 patients to weekly doses of dupilumab and 39 to weekly placebo injections for 24 weeks.
In part B, they randomly divided patients into three groups: Eighty received dupilumab weekly; 81 received dupilumab every 2 weeks; and 79 received a placebo weekly, for 24 weeks.
In part C, the intervention and placebo groups from part A received dupilumab weekly for another 28 weeks. For the two intervention groups in part B, treatment remained the same, while the part B placebo group was evenly split to receive dupilumab weekly or every 2 weeks for 28 weeks.
Over half of patients in remission
In part A, 60% of patients receiving weekly dupilumab achieved histologic remission (defined as no more than six eosinophils per high-power field), compared with 5% of patients receiving placebo, a significant difference (P < .001).
In part B, 59% of patients receiving weekly dupilumab, 60% of those receiving biweekly dupilumab, and 6% of those receiving placebo achieved histologic remission. The difference between those receiving weekly dupilumab or placebo was significant (P < .001).
Symptoms improved with weekly dupilumab, as measured via the Dysphagia Symptom Questionnaire score, which can range from 0 to 84, with higher values indicating more frequent or more severe dysphagia. The mean score at baseline was 33.6 in part A and 36.7 in part B. Scores in patients receiving weekly dupilumab decreased by 12.3 in part A and 9.9 in part B (both P < .001). However, among part B patients receiving biweekly dupilumab, the mean score dropped by only 0.5, which was not significant.
Dupilumab reached a higher serum concentration with the weekly than the biweekly regimen, which may explain the improved symptoms with more frequent dosing, Dr. Dellon said.
Only nine patients experienced serious adverse events during the part A or B treatment period (seven who received weekly dupilumab, one who received biweekly dupilumab, and one who received placebo) and just one patient during the part C treatment period who received placebo in part A and weekly dupilumab in part C. None of these events, except one, were related to the regimen, according to investigators.
Patients who received weekly dupilumab in part A and continued to part C maintained similar treatment effects to week 52, Dr. Dellon said. Although the data on part B patients who continued into part C were not included in the published paper, they were similar, he said.
“The people who responded to the first 24 weeks maintain that response for up to 52 weeks, and there was even a gain of response for some measures,” he said.
Patients, on average, also experienced improvements as measured by endoscopic healing, histological severity scores, and even gene expression, Dr. Dellon said.
‘Welcome addition’
Dupilumab is “a welcome addition to what we do,” said Philip Katz, MD, a professor of medicine in the division of gastroenterology at Weill Cornell Medicine in New York. The publication of this “pivotal” trial provides reassurance about its safety and effectiveness for EoE, he added.
“Dupilumab, or Dupixent, is going to be used in my practice for people who are refractory to both PPIs and topical steroids,” Dr. Katz, who was not involved in the research, said in an interview.
However, it will take practice to know how best to use the drug, and its high cost may make some payers reluctant to cover it, Dr. Katz added.
The study was funded by Sanofi and Regeneron. Dr. Dellon has reported financial relationships with multiple pharmaceutical companies, including Regeneron and Sanofi US. Dr. Katz has reported financial relationships with Phantom Pharmaceuticals, AstraZeneca, and Braintree Laboratories.
A version of this article first appeared on Medscape.com.
Few side effects, other than injection pain, emerged in the year-long phase 3 trial that convinced the Food and Drug Administration to approve the drug for EoE in May, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.
The FDA approved dupilumab for the treatment of EoE in people 12 years and older who weigh at least 40 kg (about 88 pounds). The study included patients who had failed to benefit from an 8-week course of high-dose proton pump inhibitor (PPI) therapy, and most also hadn’t had relief from topical steroids.
Because dupilumab is a systemic biologic, such patients are the most likely candidates for the medication, Dr. Dellon said.
Dr. Dellon and colleagues published the study results in the New England Journal of Medicine.
A chronic, progressive, type 2 inflammatory disease of the esophagus, EoE can make it difficult to swallow and cause abdominal and chest pain or vomiting. Specialized diets, topical steroids, and PPIs can help manage EoE for many patients, but these therapies don’t always work, diets are difficult to follow, and topical steroids and PPIs can be difficult to take or cause side effects.
A fully human monoclonal antibody developed by Regeneron Pharmaceuticals and Sanofi, dupilumab blocks the shared receptor component for interleukin-4 and interleukin-13, central drivers of type 2 inflammation in EoE. The FDA has approved dupilumab for atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps.
Three-part trial
For the three-part study conducted in Australia, Canada, Europe, and the United States, participants received 300 mg dupilumab by subcutaneous injection.
In part A, investigators randomly assigned 42 patients to weekly doses of dupilumab and 39 to weekly placebo injections for 24 weeks.
In part B, they randomly divided patients into three groups: Eighty received dupilumab weekly; 81 received dupilumab every 2 weeks; and 79 received a placebo weekly, for 24 weeks.
In part C, the intervention and placebo groups from part A received dupilumab weekly for another 28 weeks. For the two intervention groups in part B, treatment remained the same, while the part B placebo group was evenly split to receive dupilumab weekly or every 2 weeks for 28 weeks.
Over half of patients in remission
In part A, 60% of patients receiving weekly dupilumab achieved histologic remission (defined as no more than six eosinophils per high-power field), compared with 5% of patients receiving placebo, a significant difference (P < .001).
In part B, 59% of patients receiving weekly dupilumab, 60% of those receiving biweekly dupilumab, and 6% of those receiving placebo achieved histologic remission. The difference between those receiving weekly dupilumab or placebo was significant (P < .001).
Symptoms improved with weekly dupilumab, as measured via the Dysphagia Symptom Questionnaire score, which can range from 0 to 84, with higher values indicating more frequent or more severe dysphagia. The mean score at baseline was 33.6 in part A and 36.7 in part B. Scores in patients receiving weekly dupilumab decreased by 12.3 in part A and 9.9 in part B (both P < .001). However, among part B patients receiving biweekly dupilumab, the mean score dropped by only 0.5, which was not significant.
Dupilumab reached a higher serum concentration with the weekly than the biweekly regimen, which may explain the improved symptoms with more frequent dosing, Dr. Dellon said.
Only nine patients experienced serious adverse events during the part A or B treatment period (seven who received weekly dupilumab, one who received biweekly dupilumab, and one who received placebo) and just one patient during the part C treatment period who received placebo in part A and weekly dupilumab in part C. None of these events, except one, were related to the regimen, according to investigators.
Patients who received weekly dupilumab in part A and continued to part C maintained similar treatment effects to week 52, Dr. Dellon said. Although the data on part B patients who continued into part C were not included in the published paper, they were similar, he said.
“The people who responded to the first 24 weeks maintain that response for up to 52 weeks, and there was even a gain of response for some measures,” he said.
Patients, on average, also experienced improvements as measured by endoscopic healing, histological severity scores, and even gene expression, Dr. Dellon said.
‘Welcome addition’
Dupilumab is “a welcome addition to what we do,” said Philip Katz, MD, a professor of medicine in the division of gastroenterology at Weill Cornell Medicine in New York. The publication of this “pivotal” trial provides reassurance about its safety and effectiveness for EoE, he added.
“Dupilumab, or Dupixent, is going to be used in my practice for people who are refractory to both PPIs and topical steroids,” Dr. Katz, who was not involved in the research, said in an interview.
However, it will take practice to know how best to use the drug, and its high cost may make some payers reluctant to cover it, Dr. Katz added.
The study was funded by Sanofi and Regeneron. Dr. Dellon has reported financial relationships with multiple pharmaceutical companies, including Regeneron and Sanofi US. Dr. Katz has reported financial relationships with Phantom Pharmaceuticals, AstraZeneca, and Braintree Laboratories.
A version of this article first appeared on Medscape.com.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Stem cell transplant superior to DMTs for secondary progressive MS
new research suggests.
Results from a retrospective study show that more than 60% of patients with SPMS who received AHSCT were free from disability progression at 5 years. Also for these patients, improvement was more likely to be maintained for years after treatment.
The investigators noted that patients with secondary progressive disease often show little benefit from other DMTs, so interest in other treatments is high. While AHSCT is known to offer good results for patients with relapsing remitting MS, studies of its efficacy for SPMS have yielded conflicting results.
The new findings suggest it may be time to take another look at this therapy for patients with active, more severe disease, the researchers wrote.
“AHSCT may become a treatment option in secondary progressive MS patients with inflammatory activity who have failed available treatments,” said coinvestigator Matilde Inglese, MD, PhD, professor of neurology at the University of Genoa (Italy).
“Patients selection is very important to ensure the best treatment response and minimize safety issues, including transplant-related mortality,” Dr. Inglese added.
The findings were published online in Neurology.
Class III evidence
In the retrospective, propensity-matching study, researchers used two Italian registries to identify 79 patients who were treated off label with AHSCT and 1,975 patients who received another therapy.
Other DMTs included in the control-group analysis were beta-interferons, azathioprine, glatiramer acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, or alemtuzumab.
Results showed that time to first disability progression was significantly longer for patients who had received transplants (hazard ratio, 0.5; P = .005); 61.7% of the AHSCT group were free of disability progression at 5 years versus 46.3% of the control group.
Among patients who received AHSCT, relapse rates were lower in comparison with those who received other DMTs (P < .001), and disability scores were lower over 10 years (P < .001).
The transplant group was also significantly more likely than the other-DMTs group to achieve sustained improvement in disability 3 years after treatment (34.7% vs. 4.6%; P < .001).
“This study provides Class III evidence that autologous hematopoietic stem cell transplants prolonged the time to confirmed disability progression compared to other disease-modifying therapies,” the investigators wrote.
Extends the treatment population
Commenting on the study, Jeff Cohen, MD, director of experimental therapeutics at the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, said the research “extends the population for which hematopoietic stem cell transplant should be considered.”
Although previous studies did not show a benefit for patients with severe progressive MS, participants in the current study had secondary progressive MS and superimposed relapse activity, said Dr. Cohen, who was not involved with the research.
“We think that indicates a greater likelihood of benefit” from AHSCT, he noted. “The fact that someone has overt progression or somewhat more severe disability doesn’t preclude the use of stem cell transplant.”
Dr. Cohen pointed out, however, that the study is not without limitations. The exclusion of patients taking B-cell therapies from the SPMS control group raises the question of whether similar results would come from a comparison with AHSCT.
In addition, Dr. Cohen noted there are safety concerns about the therapy, which has yielded higher transplant-related mortality among patients with SPMS – although only one patient in the current study died following the transplant.
Still, the findings are promising, Dr. Cohen added.
“I think as more data accumulate that supports its benefit and reasonable safety in a variety of populations, we’ll see it used more,” he said.
The study was funded by the Italian Multiple Sclerosis Foundation. Dr. Inglese has received fees for consultation from Roche, Genzyme, Merck, Biogen, and Novartis. Dr. Cohen reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Results from a retrospective study show that more than 60% of patients with SPMS who received AHSCT were free from disability progression at 5 years. Also for these patients, improvement was more likely to be maintained for years after treatment.
The investigators noted that patients with secondary progressive disease often show little benefit from other DMTs, so interest in other treatments is high. While AHSCT is known to offer good results for patients with relapsing remitting MS, studies of its efficacy for SPMS have yielded conflicting results.
The new findings suggest it may be time to take another look at this therapy for patients with active, more severe disease, the researchers wrote.
“AHSCT may become a treatment option in secondary progressive MS patients with inflammatory activity who have failed available treatments,” said coinvestigator Matilde Inglese, MD, PhD, professor of neurology at the University of Genoa (Italy).
“Patients selection is very important to ensure the best treatment response and minimize safety issues, including transplant-related mortality,” Dr. Inglese added.
The findings were published online in Neurology.
Class III evidence
In the retrospective, propensity-matching study, researchers used two Italian registries to identify 79 patients who were treated off label with AHSCT and 1,975 patients who received another therapy.
Other DMTs included in the control-group analysis were beta-interferons, azathioprine, glatiramer acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, or alemtuzumab.
Results showed that time to first disability progression was significantly longer for patients who had received transplants (hazard ratio, 0.5; P = .005); 61.7% of the AHSCT group were free of disability progression at 5 years versus 46.3% of the control group.
Among patients who received AHSCT, relapse rates were lower in comparison with those who received other DMTs (P < .001), and disability scores were lower over 10 years (P < .001).
The transplant group was also significantly more likely than the other-DMTs group to achieve sustained improvement in disability 3 years after treatment (34.7% vs. 4.6%; P < .001).
“This study provides Class III evidence that autologous hematopoietic stem cell transplants prolonged the time to confirmed disability progression compared to other disease-modifying therapies,” the investigators wrote.
Extends the treatment population
Commenting on the study, Jeff Cohen, MD, director of experimental therapeutics at the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, said the research “extends the population for which hematopoietic stem cell transplant should be considered.”
Although previous studies did not show a benefit for patients with severe progressive MS, participants in the current study had secondary progressive MS and superimposed relapse activity, said Dr. Cohen, who was not involved with the research.
“We think that indicates a greater likelihood of benefit” from AHSCT, he noted. “The fact that someone has overt progression or somewhat more severe disability doesn’t preclude the use of stem cell transplant.”
Dr. Cohen pointed out, however, that the study is not without limitations. The exclusion of patients taking B-cell therapies from the SPMS control group raises the question of whether similar results would come from a comparison with AHSCT.
In addition, Dr. Cohen noted there are safety concerns about the therapy, which has yielded higher transplant-related mortality among patients with SPMS – although only one patient in the current study died following the transplant.
Still, the findings are promising, Dr. Cohen added.
“I think as more data accumulate that supports its benefit and reasonable safety in a variety of populations, we’ll see it used more,” he said.
The study was funded by the Italian Multiple Sclerosis Foundation. Dr. Inglese has received fees for consultation from Roche, Genzyme, Merck, Biogen, and Novartis. Dr. Cohen reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Results from a retrospective study show that more than 60% of patients with SPMS who received AHSCT were free from disability progression at 5 years. Also for these patients, improvement was more likely to be maintained for years after treatment.
The investigators noted that patients with secondary progressive disease often show little benefit from other DMTs, so interest in other treatments is high. While AHSCT is known to offer good results for patients with relapsing remitting MS, studies of its efficacy for SPMS have yielded conflicting results.
The new findings suggest it may be time to take another look at this therapy for patients with active, more severe disease, the researchers wrote.
“AHSCT may become a treatment option in secondary progressive MS patients with inflammatory activity who have failed available treatments,” said coinvestigator Matilde Inglese, MD, PhD, professor of neurology at the University of Genoa (Italy).
“Patients selection is very important to ensure the best treatment response and minimize safety issues, including transplant-related mortality,” Dr. Inglese added.
The findings were published online in Neurology.
Class III evidence
In the retrospective, propensity-matching study, researchers used two Italian registries to identify 79 patients who were treated off label with AHSCT and 1,975 patients who received another therapy.
Other DMTs included in the control-group analysis were beta-interferons, azathioprine, glatiramer acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, or alemtuzumab.
Results showed that time to first disability progression was significantly longer for patients who had received transplants (hazard ratio, 0.5; P = .005); 61.7% of the AHSCT group were free of disability progression at 5 years versus 46.3% of the control group.
Among patients who received AHSCT, relapse rates were lower in comparison with those who received other DMTs (P < .001), and disability scores were lower over 10 years (P < .001).
The transplant group was also significantly more likely than the other-DMTs group to achieve sustained improvement in disability 3 years after treatment (34.7% vs. 4.6%; P < .001).
“This study provides Class III evidence that autologous hematopoietic stem cell transplants prolonged the time to confirmed disability progression compared to other disease-modifying therapies,” the investigators wrote.
Extends the treatment population
Commenting on the study, Jeff Cohen, MD, director of experimental therapeutics at the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, said the research “extends the population for which hematopoietic stem cell transplant should be considered.”
Although previous studies did not show a benefit for patients with severe progressive MS, participants in the current study had secondary progressive MS and superimposed relapse activity, said Dr. Cohen, who was not involved with the research.
“We think that indicates a greater likelihood of benefit” from AHSCT, he noted. “The fact that someone has overt progression or somewhat more severe disability doesn’t preclude the use of stem cell transplant.”
Dr. Cohen pointed out, however, that the study is not without limitations. The exclusion of patients taking B-cell therapies from the SPMS control group raises the question of whether similar results would come from a comparison with AHSCT.
In addition, Dr. Cohen noted there are safety concerns about the therapy, which has yielded higher transplant-related mortality among patients with SPMS – although only one patient in the current study died following the transplant.
Still, the findings are promising, Dr. Cohen added.
“I think as more data accumulate that supports its benefit and reasonable safety in a variety of populations, we’ll see it used more,” he said.
The study was funded by the Italian Multiple Sclerosis Foundation. Dr. Inglese has received fees for consultation from Roche, Genzyme, Merck, Biogen, and Novartis. Dr. Cohen reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
STEMI times to treatment usually miss established goals
Therapy initiated within national treatment-time goals set a decade ago for patients with ST-segment elevation myocardial infarction (STEMI) remains associated with improved survival in recent years. But for many such patients, time from first symptoms to initiation of reperfusion therapy still fails to meet those goals, suggests a cross-sectional registry analysis.
For example, patients initially transported to centers with percutaneous coronary intervention (PCI) capability had a median treatment time of 148 minutes, in the analysis spanning the second quarter (Q2) of 2018 to the third quarter (Q3) of 2021. But the goal for centers called for treatment initiation within 90 minutes for at least 75% of such STEMI patients.
Moreover, overall STEMI treatment times and in-hospital mortality rose in tandem significantly from Q2 2018 through the first quarter (Q1) of 2021, which included the first year of the COVID-19 pandemic. Median time to treatment went from 86 minutes to 91 minutes during that period. Meanwhile, in-hospital mortality went from 5.6% to 8.7%, report the study authors led by James G. Jollis, MD, Duke University, Durham, N.C.
Their report, based on 114,871 STEMI patients at 601 US hospitals contributing to the Get With The Guidelines – Coronary Artery Disease registry, was published online in JAMA.
Of those patients, 25,085 had been transferred from non-PCI hospitals, 32,483 were walk-ins, and 57,303 arrived via emergency medical services (EMS). Their median times from symptom onset to PCI were 240, 195, and 148 minutes, respectively.
In-hospital mortality was significantly reduced in an adjusted analysis for patients treated within target times, compared with those whose treatment missed the time goals, regardless of whether they were transported by EMS, walked into a hospital with on-site PCI, or were transferred from a non-PCI center (Table 1).
Regardless of mode of patient presentation, treatment time goals were not met most of the time, the group reports. Patients who required interhospital transfer experienced the longest system delays; only 17% were treated within 120 minutes.
Among patients who received primary PCI, 20% had a registry-defined hospital-specified reason for delay, including cardiac arrest and/or need for intubation in 6.8%, “difficulty crossing the culprit lesion” in 3.8%, and “other reasons” in 5.8%, the group reports.
“In 2020, a new reason for delay was added to the registry, ‘need for additional personal protective equipment for suspected/confirmed infectious disease.’ This reason was most commonly used in the second quarter of 2020 (6%) and then declined over time to 1% in the final 2 quarters,” they write.
“Thus, active SARS-CoV-2 infection appeared to have a smaller direct role in longer treatment times or worse outcomes.” Rather, they continue, “the pandemic potentially had a significant indirect role as hospitals were overwhelmed with patients, EMS and hospitals were challenged in maintaining paramedic and nurse staffing and intensive care bed availability, and patients experienced delayed care due to barriers to access or perceived fear of becoming entangled in an overwhelmed medical system.”
Still an important quality metric
STEMI treatment times remain an important quality metric to which hospitals should continue to pay attention because shorter times improve patient care, Deepak Bhatt, MD, MPH, told this news organization.
“Having said that, as with all metrics, one needs to be thoughtful and realize that a difference of a couple of minutes is probably not a crucial thing,” said Dr. Bhatt, Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved with the current study.
Interhospital transfers indeed involve longer delays, he observed, suggesting that regional integrated health systems should develop methods for optimizing STEMI care – even, for example, if they involve bypassing non-PCI centers or stopping patients briefly for stabilization followed by rapid transport to a PCI-capable facility.
“That, of course, requires cooperation among hospitals. Sometimes that requires hospitals putting aside economic considerations and just focusing on doing the right thing for that individual patient,” Dr. Bhatt said.
Transfer delays are common for patients presenting with STEMI at hospitals without PCI capability, he noted. “Having clear protocols in place that expedite that type of transfer, I think, could go a long way in reducing the time to treatment in patients that are presenting to the hospital without cath labs. That’s an important message that these data provide.”
The onset of COVID-19 led to widespread delays in STEMI time to treatment early in the pandemic. There were concerns about exposing cath lab personnel to SARS-CoV-2 and potential adverse consequences of sick personnel being unable to provide patient care in the subsequent weeks and months, Dr. Bhatt observed.
However, “All of that seems to have quieted down, and I don’t think COVID is impacting time to treatment right now.”
‘Suboptimal compliance’ with standards
The current findings of “suboptimal compliance with national targets underscore why reassessing quality metrics, in light of changing practice patterns and other secular trends, is critical,” write Andrew S. Oseran, MD, MBA, and Robert W. Yeh, MD, both of Harvard Medical School, in an accompanying editorial.
“While the importance of coordinated and expeditious care for this high-risk patient population is undeniable, the specific actions that hospitals can – or should – take to further improve overall STEMI outcomes are less clear,” they say.
“As physicians contemplate the optimal path forward in managing the care of STEMI patients, they must recognize the clinical and operational nuance that exists in caring for this diverse population and acknowledge the trade-offs associated with uniform quality metrics,” write the editorialists.
“Global reductions in time to treatment for STEMI patients has been one of health care’s great success stories. As we move forward, it may be time to consider whether efforts to achieve additional improvement in target treatment times will result in substantive benefits, or whether we have reached the point of diminishing returns.”
A version of this article first appeared on Medscape.com.
Therapy initiated within national treatment-time goals set a decade ago for patients with ST-segment elevation myocardial infarction (STEMI) remains associated with improved survival in recent years. But for many such patients, time from first symptoms to initiation of reperfusion therapy still fails to meet those goals, suggests a cross-sectional registry analysis.
For example, patients initially transported to centers with percutaneous coronary intervention (PCI) capability had a median treatment time of 148 minutes, in the analysis spanning the second quarter (Q2) of 2018 to the third quarter (Q3) of 2021. But the goal for centers called for treatment initiation within 90 minutes for at least 75% of such STEMI patients.
Moreover, overall STEMI treatment times and in-hospital mortality rose in tandem significantly from Q2 2018 through the first quarter (Q1) of 2021, which included the first year of the COVID-19 pandemic. Median time to treatment went from 86 minutes to 91 minutes during that period. Meanwhile, in-hospital mortality went from 5.6% to 8.7%, report the study authors led by James G. Jollis, MD, Duke University, Durham, N.C.
Their report, based on 114,871 STEMI patients at 601 US hospitals contributing to the Get With The Guidelines – Coronary Artery Disease registry, was published online in JAMA.
Of those patients, 25,085 had been transferred from non-PCI hospitals, 32,483 were walk-ins, and 57,303 arrived via emergency medical services (EMS). Their median times from symptom onset to PCI were 240, 195, and 148 minutes, respectively.
In-hospital mortality was significantly reduced in an adjusted analysis for patients treated within target times, compared with those whose treatment missed the time goals, regardless of whether they were transported by EMS, walked into a hospital with on-site PCI, or were transferred from a non-PCI center (Table 1).
Regardless of mode of patient presentation, treatment time goals were not met most of the time, the group reports. Patients who required interhospital transfer experienced the longest system delays; only 17% were treated within 120 minutes.
Among patients who received primary PCI, 20% had a registry-defined hospital-specified reason for delay, including cardiac arrest and/or need for intubation in 6.8%, “difficulty crossing the culprit lesion” in 3.8%, and “other reasons” in 5.8%, the group reports.
“In 2020, a new reason for delay was added to the registry, ‘need for additional personal protective equipment for suspected/confirmed infectious disease.’ This reason was most commonly used in the second quarter of 2020 (6%) and then declined over time to 1% in the final 2 quarters,” they write.
“Thus, active SARS-CoV-2 infection appeared to have a smaller direct role in longer treatment times or worse outcomes.” Rather, they continue, “the pandemic potentially had a significant indirect role as hospitals were overwhelmed with patients, EMS and hospitals were challenged in maintaining paramedic and nurse staffing and intensive care bed availability, and patients experienced delayed care due to barriers to access or perceived fear of becoming entangled in an overwhelmed medical system.”
Still an important quality metric
STEMI treatment times remain an important quality metric to which hospitals should continue to pay attention because shorter times improve patient care, Deepak Bhatt, MD, MPH, told this news organization.
“Having said that, as with all metrics, one needs to be thoughtful and realize that a difference of a couple of minutes is probably not a crucial thing,” said Dr. Bhatt, Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved with the current study.
Interhospital transfers indeed involve longer delays, he observed, suggesting that regional integrated health systems should develop methods for optimizing STEMI care – even, for example, if they involve bypassing non-PCI centers or stopping patients briefly for stabilization followed by rapid transport to a PCI-capable facility.
“That, of course, requires cooperation among hospitals. Sometimes that requires hospitals putting aside economic considerations and just focusing on doing the right thing for that individual patient,” Dr. Bhatt said.
Transfer delays are common for patients presenting with STEMI at hospitals without PCI capability, he noted. “Having clear protocols in place that expedite that type of transfer, I think, could go a long way in reducing the time to treatment in patients that are presenting to the hospital without cath labs. That’s an important message that these data provide.”
The onset of COVID-19 led to widespread delays in STEMI time to treatment early in the pandemic. There were concerns about exposing cath lab personnel to SARS-CoV-2 and potential adverse consequences of sick personnel being unable to provide patient care in the subsequent weeks and months, Dr. Bhatt observed.
However, “All of that seems to have quieted down, and I don’t think COVID is impacting time to treatment right now.”
‘Suboptimal compliance’ with standards
The current findings of “suboptimal compliance with national targets underscore why reassessing quality metrics, in light of changing practice patterns and other secular trends, is critical,” write Andrew S. Oseran, MD, MBA, and Robert W. Yeh, MD, both of Harvard Medical School, in an accompanying editorial.
“While the importance of coordinated and expeditious care for this high-risk patient population is undeniable, the specific actions that hospitals can – or should – take to further improve overall STEMI outcomes are less clear,” they say.
“As physicians contemplate the optimal path forward in managing the care of STEMI patients, they must recognize the clinical and operational nuance that exists in caring for this diverse population and acknowledge the trade-offs associated with uniform quality metrics,” write the editorialists.
“Global reductions in time to treatment for STEMI patients has been one of health care’s great success stories. As we move forward, it may be time to consider whether efforts to achieve additional improvement in target treatment times will result in substantive benefits, or whether we have reached the point of diminishing returns.”
A version of this article first appeared on Medscape.com.
Therapy initiated within national treatment-time goals set a decade ago for patients with ST-segment elevation myocardial infarction (STEMI) remains associated with improved survival in recent years. But for many such patients, time from first symptoms to initiation of reperfusion therapy still fails to meet those goals, suggests a cross-sectional registry analysis.
For example, patients initially transported to centers with percutaneous coronary intervention (PCI) capability had a median treatment time of 148 minutes, in the analysis spanning the second quarter (Q2) of 2018 to the third quarter (Q3) of 2021. But the goal for centers called for treatment initiation within 90 minutes for at least 75% of such STEMI patients.
Moreover, overall STEMI treatment times and in-hospital mortality rose in tandem significantly from Q2 2018 through the first quarter (Q1) of 2021, which included the first year of the COVID-19 pandemic. Median time to treatment went from 86 minutes to 91 minutes during that period. Meanwhile, in-hospital mortality went from 5.6% to 8.7%, report the study authors led by James G. Jollis, MD, Duke University, Durham, N.C.
Their report, based on 114,871 STEMI patients at 601 US hospitals contributing to the Get With The Guidelines – Coronary Artery Disease registry, was published online in JAMA.
Of those patients, 25,085 had been transferred from non-PCI hospitals, 32,483 were walk-ins, and 57,303 arrived via emergency medical services (EMS). Their median times from symptom onset to PCI were 240, 195, and 148 minutes, respectively.
In-hospital mortality was significantly reduced in an adjusted analysis for patients treated within target times, compared with those whose treatment missed the time goals, regardless of whether they were transported by EMS, walked into a hospital with on-site PCI, or were transferred from a non-PCI center (Table 1).
Regardless of mode of patient presentation, treatment time goals were not met most of the time, the group reports. Patients who required interhospital transfer experienced the longest system delays; only 17% were treated within 120 minutes.
Among patients who received primary PCI, 20% had a registry-defined hospital-specified reason for delay, including cardiac arrest and/or need for intubation in 6.8%, “difficulty crossing the culprit lesion” in 3.8%, and “other reasons” in 5.8%, the group reports.
“In 2020, a new reason for delay was added to the registry, ‘need for additional personal protective equipment for suspected/confirmed infectious disease.’ This reason was most commonly used in the second quarter of 2020 (6%) and then declined over time to 1% in the final 2 quarters,” they write.
“Thus, active SARS-CoV-2 infection appeared to have a smaller direct role in longer treatment times or worse outcomes.” Rather, they continue, “the pandemic potentially had a significant indirect role as hospitals were overwhelmed with patients, EMS and hospitals were challenged in maintaining paramedic and nurse staffing and intensive care bed availability, and patients experienced delayed care due to barriers to access or perceived fear of becoming entangled in an overwhelmed medical system.”
Still an important quality metric
STEMI treatment times remain an important quality metric to which hospitals should continue to pay attention because shorter times improve patient care, Deepak Bhatt, MD, MPH, told this news organization.
“Having said that, as with all metrics, one needs to be thoughtful and realize that a difference of a couple of minutes is probably not a crucial thing,” said Dr. Bhatt, Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved with the current study.
Interhospital transfers indeed involve longer delays, he observed, suggesting that regional integrated health systems should develop methods for optimizing STEMI care – even, for example, if they involve bypassing non-PCI centers or stopping patients briefly for stabilization followed by rapid transport to a PCI-capable facility.
“That, of course, requires cooperation among hospitals. Sometimes that requires hospitals putting aside economic considerations and just focusing on doing the right thing for that individual patient,” Dr. Bhatt said.
Transfer delays are common for patients presenting with STEMI at hospitals without PCI capability, he noted. “Having clear protocols in place that expedite that type of transfer, I think, could go a long way in reducing the time to treatment in patients that are presenting to the hospital without cath labs. That’s an important message that these data provide.”
The onset of COVID-19 led to widespread delays in STEMI time to treatment early in the pandemic. There were concerns about exposing cath lab personnel to SARS-CoV-2 and potential adverse consequences of sick personnel being unable to provide patient care in the subsequent weeks and months, Dr. Bhatt observed.
However, “All of that seems to have quieted down, and I don’t think COVID is impacting time to treatment right now.”
‘Suboptimal compliance’ with standards
The current findings of “suboptimal compliance with national targets underscore why reassessing quality metrics, in light of changing practice patterns and other secular trends, is critical,” write Andrew S. Oseran, MD, MBA, and Robert W. Yeh, MD, both of Harvard Medical School, in an accompanying editorial.
“While the importance of coordinated and expeditious care for this high-risk patient population is undeniable, the specific actions that hospitals can – or should – take to further improve overall STEMI outcomes are less clear,” they say.
“As physicians contemplate the optimal path forward in managing the care of STEMI patients, they must recognize the clinical and operational nuance that exists in caring for this diverse population and acknowledge the trade-offs associated with uniform quality metrics,” write the editorialists.
“Global reductions in time to treatment for STEMI patients has been one of health care’s great success stories. As we move forward, it may be time to consider whether efforts to achieve additional improvement in target treatment times will result in substantive benefits, or whether we have reached the point of diminishing returns.”
A version of this article first appeared on Medscape.com.
FROM JAMA
Innovations in Dermatology Fall Abstract Compendium
Fourth Study to Show Consistent Benefit of Highly Purified Eicosapentaenoic Acid on Cardiovascular Outcomes: Results From RESPECT-EPA
In this supplement to Cardiology News, John R. Nelson, MD, FACC, FNLA, FASNC, and Matthew J. Budoff, MD, discuss results from RESPECT-EPA and the existing evidence that purified eicosapentaenoic acid significantly reduces residual CV risk in patients with CVD.
In this supplement to Cardiology News, John R. Nelson, MD, FACC, FNLA, FASNC, and Matthew J. Budoff, MD, discuss results from RESPECT-EPA and the existing evidence that purified eicosapentaenoic acid significantly reduces residual CV risk in patients with CVD.
In this supplement to Cardiology News, John R. Nelson, MD, FACC, FNLA, FASNC, and Matthew J. Budoff, MD, discuss results from RESPECT-EPA and the existing evidence that purified eicosapentaenoic acid significantly reduces residual CV risk in patients with CVD.
“The Nail in the Coffin for Fibrates”: Futility of PROMINENT Trial Definitively Settles Debate on Avoiding Use of Fibrate Class of Medications for Cardiovascular Risk Reduction
In this supplement to Cardiology News, Payal Kohli, MD, FACC, and Nihar Desai, MD, MPH, discuss the PROMINENT trial and the debate on avoiding the use of fibrates for cardiovascular risk reduction.
In this supplement to Cardiology News, Payal Kohli, MD, FACC, and Nihar Desai, MD, MPH, discuss the PROMINENT trial and the debate on avoiding the use of fibrates for cardiovascular risk reduction.
In this supplement to Cardiology News, Payal Kohli, MD, FACC, and Nihar Desai, MD, MPH, discuss the PROMINENT trial and the debate on avoiding the use of fibrates for cardiovascular risk reduction.
Prodromal Parkinson’s disease tied to significant functional impairment
new research shows.
The new findings come from a large case-control study that analyzed Medicare claims data to evaluate functional limitations in prodromal Parkinson’s disease, leading the investigators to suggest prodromal Parkinson’s disease should be recognized as a distinct disease stage.
“It’s increasingly recognized as a stage of Parkinson’s and there is an argument here for that,” said lead investigator Cameron Miller-Patterson, MD, assistant professor of neurology at Virginia Commonwealth University, Richmond. “Because we’re finding that people with prodromal Parkinson’s disease may have functional limitations, identifying them sooner and getting them the appropriate symptomatic therapy could be helpful.”
The findings were published online in JAMA Neurology.
Improving quality of life
Individuals with prodromal Parkinson’s disease have symptoms of Parkinson’s disease, but not enough to meet diagnostic criteria. However, all patients with prodromal Parkinson’s disease eventually meet that threshold.
To evaluate whether functional limitations are present in individuals with Parkinson’s disease prior to diagnosis versus the general population, researchers analyzed Medicare-linked data on 6,674 individuals aged 65 years and older who participated in the National Health and Aging Trends Study, a longitudinal survey in the United States. Survey questions evaluated dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision.
Patients with incident Parkinson’s disease were defined as having two or more Medicare diagnoses. Controls were defined as those with Medicare eligibility at baseline and 2 or more years prior, with no diagnosis.
Compared with individuals who never had Parkinson’s disease, those who eventually received a diagnosis were less likely to report being able to walk 6 blocks (odds ratio, 0.34; 95% confidence interval, 0.15-0.82), stand independently from kneeling (OR, 0.30; 95% CI, 0.11-0.85) or lift a heavy object overhead (OR, 0.36; 95% CI, 0.15-0.87). They were also more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis.
“Generally, we don’t start treating people until we see them in the clinic and give them a diagnosis of Parkinson’s disease,” Dr. Miller-Patterson said. “If we identify them earlier, even before diagnosis, we may be able to improve their quality of life by treating them sooner.”
Serving patients better
Better recognition of prodromal Parkinson’s disease could also help identify participants for clinical trials of therapeutics that could slow disease progression, something that is beyond the ability of currently approved medications.
This, and growing support for distinguishing prodromal Parkinson’s disease as an official stage of Parkinson’s disease, makes findings such as these both timely and important, the authors of an accompanying commentary wrote .
“The recognition of a prodromal period has been viewed as potentially critical to the success of disease-modifying interventions, on the argument that it may be too late to enact meaningful clinical change once symptoms clinically manifest given the degree of neurodegeneration already present,” Ian O. Bledsoe, MD, Weill Institute for Neurosciences, University of California, San Francisco, and coauthors wrote.
One limitation, however, is that the study design didn’t allow researchers to determine if individuals with eventual Parkinson’s disease who reported parkinsonian symptoms had prodromal Parkinson’s disease or undiagnosed disease. The answer would clarify whether prodromal Parkinson’s disease is more common than previously thought or if Parkinson’s disease diagnosis is often delayed for years – or both.
“Despite the limitations of this study, its broader point and importance remain: People appear to have some markers of functional decline before they are diagnosed with Parkinson’s disease,” the editorialists wrote. “Additionally, motor dysfunction may arise at an earlier time point in the disease than we typically think. There is a potential opportunity to serve this population better.”
The study was funded by the National Institutes of Health. Dr. Miller-Patterson reported receiving other NIH grants during the course of the study. Dr. Bledsoe reported personal fees from Boston Scientific, Amneal Pharmaceuticals, IDEO, Accorda, Humancraft.com, and Putnam Associates, as well as grants from the National Institutes of Health, the Michael J. Fox Foundation, and Dystonia Medical.
A version of this article first appeared on Medscape.com.
new research shows.
The new findings come from a large case-control study that analyzed Medicare claims data to evaluate functional limitations in prodromal Parkinson’s disease, leading the investigators to suggest prodromal Parkinson’s disease should be recognized as a distinct disease stage.
“It’s increasingly recognized as a stage of Parkinson’s and there is an argument here for that,” said lead investigator Cameron Miller-Patterson, MD, assistant professor of neurology at Virginia Commonwealth University, Richmond. “Because we’re finding that people with prodromal Parkinson’s disease may have functional limitations, identifying them sooner and getting them the appropriate symptomatic therapy could be helpful.”
The findings were published online in JAMA Neurology.
Improving quality of life
Individuals with prodromal Parkinson’s disease have symptoms of Parkinson’s disease, but not enough to meet diagnostic criteria. However, all patients with prodromal Parkinson’s disease eventually meet that threshold.
To evaluate whether functional limitations are present in individuals with Parkinson’s disease prior to diagnosis versus the general population, researchers analyzed Medicare-linked data on 6,674 individuals aged 65 years and older who participated in the National Health and Aging Trends Study, a longitudinal survey in the United States. Survey questions evaluated dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision.
Patients with incident Parkinson’s disease were defined as having two or more Medicare diagnoses. Controls were defined as those with Medicare eligibility at baseline and 2 or more years prior, with no diagnosis.
Compared with individuals who never had Parkinson’s disease, those who eventually received a diagnosis were less likely to report being able to walk 6 blocks (odds ratio, 0.34; 95% confidence interval, 0.15-0.82), stand independently from kneeling (OR, 0.30; 95% CI, 0.11-0.85) or lift a heavy object overhead (OR, 0.36; 95% CI, 0.15-0.87). They were also more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis.
“Generally, we don’t start treating people until we see them in the clinic and give them a diagnosis of Parkinson’s disease,” Dr. Miller-Patterson said. “If we identify them earlier, even before diagnosis, we may be able to improve their quality of life by treating them sooner.”
Serving patients better
Better recognition of prodromal Parkinson’s disease could also help identify participants for clinical trials of therapeutics that could slow disease progression, something that is beyond the ability of currently approved medications.
This, and growing support for distinguishing prodromal Parkinson’s disease as an official stage of Parkinson’s disease, makes findings such as these both timely and important, the authors of an accompanying commentary wrote .
“The recognition of a prodromal period has been viewed as potentially critical to the success of disease-modifying interventions, on the argument that it may be too late to enact meaningful clinical change once symptoms clinically manifest given the degree of neurodegeneration already present,” Ian O. Bledsoe, MD, Weill Institute for Neurosciences, University of California, San Francisco, and coauthors wrote.
One limitation, however, is that the study design didn’t allow researchers to determine if individuals with eventual Parkinson’s disease who reported parkinsonian symptoms had prodromal Parkinson’s disease or undiagnosed disease. The answer would clarify whether prodromal Parkinson’s disease is more common than previously thought or if Parkinson’s disease diagnosis is often delayed for years – or both.
“Despite the limitations of this study, its broader point and importance remain: People appear to have some markers of functional decline before they are diagnosed with Parkinson’s disease,” the editorialists wrote. “Additionally, motor dysfunction may arise at an earlier time point in the disease than we typically think. There is a potential opportunity to serve this population better.”
The study was funded by the National Institutes of Health. Dr. Miller-Patterson reported receiving other NIH grants during the course of the study. Dr. Bledsoe reported personal fees from Boston Scientific, Amneal Pharmaceuticals, IDEO, Accorda, Humancraft.com, and Putnam Associates, as well as grants from the National Institutes of Health, the Michael J. Fox Foundation, and Dystonia Medical.
A version of this article first appeared on Medscape.com.
new research shows.
The new findings come from a large case-control study that analyzed Medicare claims data to evaluate functional limitations in prodromal Parkinson’s disease, leading the investigators to suggest prodromal Parkinson’s disease should be recognized as a distinct disease stage.
“It’s increasingly recognized as a stage of Parkinson’s and there is an argument here for that,” said lead investigator Cameron Miller-Patterson, MD, assistant professor of neurology at Virginia Commonwealth University, Richmond. “Because we’re finding that people with prodromal Parkinson’s disease may have functional limitations, identifying them sooner and getting them the appropriate symptomatic therapy could be helpful.”
The findings were published online in JAMA Neurology.
Improving quality of life
Individuals with prodromal Parkinson’s disease have symptoms of Parkinson’s disease, but not enough to meet diagnostic criteria. However, all patients with prodromal Parkinson’s disease eventually meet that threshold.
To evaluate whether functional limitations are present in individuals with Parkinson’s disease prior to diagnosis versus the general population, researchers analyzed Medicare-linked data on 6,674 individuals aged 65 years and older who participated in the National Health and Aging Trends Study, a longitudinal survey in the United States. Survey questions evaluated dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision.
Patients with incident Parkinson’s disease were defined as having two or more Medicare diagnoses. Controls were defined as those with Medicare eligibility at baseline and 2 or more years prior, with no diagnosis.
Compared with individuals who never had Parkinson’s disease, those who eventually received a diagnosis were less likely to report being able to walk 6 blocks (odds ratio, 0.34; 95% confidence interval, 0.15-0.82), stand independently from kneeling (OR, 0.30; 95% CI, 0.11-0.85) or lift a heavy object overhead (OR, 0.36; 95% CI, 0.15-0.87). They were also more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis.
“Generally, we don’t start treating people until we see them in the clinic and give them a diagnosis of Parkinson’s disease,” Dr. Miller-Patterson said. “If we identify them earlier, even before diagnosis, we may be able to improve their quality of life by treating them sooner.”
Serving patients better
Better recognition of prodromal Parkinson’s disease could also help identify participants for clinical trials of therapeutics that could slow disease progression, something that is beyond the ability of currently approved medications.
This, and growing support for distinguishing prodromal Parkinson’s disease as an official stage of Parkinson’s disease, makes findings such as these both timely and important, the authors of an accompanying commentary wrote .
“The recognition of a prodromal period has been viewed as potentially critical to the success of disease-modifying interventions, on the argument that it may be too late to enact meaningful clinical change once symptoms clinically manifest given the degree of neurodegeneration already present,” Ian O. Bledsoe, MD, Weill Institute for Neurosciences, University of California, San Francisco, and coauthors wrote.
One limitation, however, is that the study design didn’t allow researchers to determine if individuals with eventual Parkinson’s disease who reported parkinsonian symptoms had prodromal Parkinson’s disease or undiagnosed disease. The answer would clarify whether prodromal Parkinson’s disease is more common than previously thought or if Parkinson’s disease diagnosis is often delayed for years – or both.
“Despite the limitations of this study, its broader point and importance remain: People appear to have some markers of functional decline before they are diagnosed with Parkinson’s disease,” the editorialists wrote. “Additionally, motor dysfunction may arise at an earlier time point in the disease than we typically think. There is a potential opportunity to serve this population better.”
The study was funded by the National Institutes of Health. Dr. Miller-Patterson reported receiving other NIH grants during the course of the study. Dr. Bledsoe reported personal fees from Boston Scientific, Amneal Pharmaceuticals, IDEO, Accorda, Humancraft.com, and Putnam Associates, as well as grants from the National Institutes of Health, the Michael J. Fox Foundation, and Dystonia Medical.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
Cervical cancer rise in White women: A ‘canary in the coal mine’
Cervical cancer appears to be rising more rapidly in White women than in Black women in the United States, according to two independent studies. Researchers puzzling over this counterintuitive finding say that, if true, the findings may be a “canary in the coal mine,” signaling problems with U.S. health care that go way beyond women’s health.
Cervical cancer incidence in the United States has plateaued since 2010 and now stands at 7.5 per 100,000 people. Well-known disparities exist: Compared with White women, Black women are more likely to have distant-stage disease at diagnosis and more commonly die of their cancer.
However, two unconnected studies published in the past 5 months suggest that White women are catching up fast.
Cervical cancer rates in White women aged 30-34 are rising 2.8% a year, but holding steady for Black women, according to a recent study led by Ashish A. Deshmukh, PhD, of the Medical University of South Carolina, Charleston. His team analyzed the 2001-2019 National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) dataset, which covers 98% of the U.S. population and 227,062 cervical cancer cases.
These findings were echoed by an analysis of the same database for 2001-2018 by the University of California, Los Angeles (UCLA), suggesting that distant-stage cervical cancer (defined as disease that has spread to the bladder and/or rectum at diagnosis) is climbing 1.69% a year in White people versus 0.67% in Black individuals.
The UCLA researchers, headed by Alex Francoeur, MD, a resident in the department of obstetrics and gynecology, found that disparities were most stark in adenocarcinoma, with an annual increase of 3.40% a year among White women and 1.71% in Black women.
Such findings have equity researchers scratching their heads. In cancer, it’s rare to see evidence that Black patients are doing better than their White counterparts.
One theoretical explanation is that the data are flawed, Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society, told this news organization. For example, the UCLA analysis may have been fogged by changes in staging definitions over time, Dr. Jemal said, although this would not explain the racial disparities per se.
Dr. Deshmukh stands by his data and said that, for him, the message is clear: “If rising incidence is not for localized-stage disease, but for advanced stages, that means it’s attributable to lack of screening,” he told this news organization.
However, this ‘simple’ explanation generates even more questions, Dr. Deshmukh said: “Screening is not a one-time procedure [but] a spectrum of timely cervical precancer treatment if [required]. We don’t know when exactly non-Hispanic White women are falling behind on that spectrum.”
The UCLA study supports Dr. Deshmukh’s conclusions. Using data from the Behavioral Risk Factor Surveillance System to calculate trends in “nonguideline screening,” the researchers found that White women were almost twice as likely to report that they were not following screening guidelines compared with Black women over the period of 2001-2016 (26.6% vs. 13.8%; P < .001).
“It’s not an artifact, it’s real,” said Timothy Rebbeck, PhD, the Vincent L. Gregory Jr. Professor of Cancer Prevention at Harvard TH Chan School of Public Health, Boston, who was not an author of either study and was approached for comment.
“The data are correct but there are so many things going on that might explain these patterns,” he told this news organization.
“This is a great example of complex changes in our social system, political system, health care system that are having really clear, measurable effects,” Dr. Rebbeck said. “Cervical cancer is almost a canary in the coal mine for some of this because it’s so preventable.”
(The saying “canary in a coal mine” is a warning of danger or trouble ahead. It comes from the time when coal miners would carry a caged canary down into the tunnels to warn them of noxious gases, which would kill the bird but give men time to escape.)
For example, Dr. Rebbeck said, recent turmoil in U.S. health care has left many people distrustful of the system. Although he acknowledged this was “high speculation,” he suggested that some women may have become less willing to participate in any mass health care intervention because of their political beliefs.
The UCLA study found that distant cervical cancer was rising fastest in middle-aged White women in the U.S. South, at a rate of 4.5% per year (P < .001).
Dr. Rebbeck also suggested that Medicaid expansion – the broadening of health insurance coverage in some states since the Affordable Care Act in 2014 – could be implicated. Of the 11 states that have not yet expanded Medicaid, eight are in the South.
“White populations who are in states that didn’t expand Medicaid are not getting a lot of the standard treatment and care that you would expect ...” Dr. Rebbeck said. “You could very well imagine that Medicaid nonexpanding states would have all kinds of patterns that would lead to more aggressive disease.”
In fact, there is already evidence that Medicaid expansion has affected racial disparities, disproportionately benefiting Black and Hispanic families, as for example, from an analysis of 65 studies by the Kaiser Family Foundation in 2020.
Commenting on these data, Dr. Rebbeck said, “Does that mean that the patterns of advanced cervical cancer had a smaller effect on Black women in this period because there was a greater shift in access to care? This is again a speculation, but it does fit with the ‘canary in a coal mine’ concept that advanced cervical cancer may be more rapidly influenced by health care access than other health conditions.”
The authors of the UCLA study suggested another explanation for their results: Differing enthusiasm for human papillomavirus (HPV) vaccination among White and Black families. The team also analyzed data on HPV vaccination, which offers protection against cervical cancer. The researchers found that vaccination rates were lowest, at 66.1%, among White teenagers aged 13-17 years, compared with Hispanics at 75.3%, Black teenagers at 74.6%, and Asians at 68.1%.
However, this theory was dismissed by both Dr. Jemal and Dr. Rebbeck due to timing. HPV vaccines have been around for approximately 15 years, so women who benefited (or didn’t benefit) from vaccination would be only in their late 20s today, they pointed out.
“Ninety-five percent of the cervical cancer cases we see now are in women who have not been vaccinated,” said Dr. Jemal, “So that’s out of the equation.”
Dr. Rebbeck agreed: “HPV may or may not be a thing here because it’s [got] such a latency.”
HPV vaccination may be out of the picture, but what about the epidemiology of HPV itself? Could the virus directly or indirectly be boosting advanced cervical cancer in White women?
Dr. Deshmukh thinks that it might be doing so.
He published an analysis of 2000-2018 SEER data showing that U.S. counties with the highest incidences of HPV-associated cancers also had the highest levels of smoking.
Other recent data suggest that middle-aged White women in the United States are more likely to reach for a smoke than are Black women.
Dr. Deshmukh acknowledges that the link is speculative but reasonable: “We don’t know exactly what the impact of smoking would be in terms of ... the ability to clear HPV infection. It may inhibit apoptosis, promoting tumor growth. There’s no causal association. It’s a cofactor risk.”
Dr. Rebbeck is also suspicious that smoking patterns might be a factor, pointing out that “smoking is certainly associated with both health behaviors and advanced cervical cancer.”
Both Dr. Rebbeck and Dr. Deshmukh concluded that, at this point, we can only speculate on what’s driving the puzzling acceleration of cervical cancer in White women in the United States.
However, whether it’s political aversion to screening, smoking-boosted HPV infection, Medicaid expansion or lack of it, or something else, they all agree that this canary in the coal mine clearly needs urgent medical attention.
Dr. Rebbeck and Dr. Jemal have declared no conflicts of interest. Dr. Deshmukh has declared consultant or advisory roles for Merck and Value Analytics Labs. None of the authors of the UCLA study have declared competing interests.
A version of this article first appeared on Medscape.com.
Cervical cancer appears to be rising more rapidly in White women than in Black women in the United States, according to two independent studies. Researchers puzzling over this counterintuitive finding say that, if true, the findings may be a “canary in the coal mine,” signaling problems with U.S. health care that go way beyond women’s health.
Cervical cancer incidence in the United States has plateaued since 2010 and now stands at 7.5 per 100,000 people. Well-known disparities exist: Compared with White women, Black women are more likely to have distant-stage disease at diagnosis and more commonly die of their cancer.
However, two unconnected studies published in the past 5 months suggest that White women are catching up fast.
Cervical cancer rates in White women aged 30-34 are rising 2.8% a year, but holding steady for Black women, according to a recent study led by Ashish A. Deshmukh, PhD, of the Medical University of South Carolina, Charleston. His team analyzed the 2001-2019 National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) dataset, which covers 98% of the U.S. population and 227,062 cervical cancer cases.
These findings were echoed by an analysis of the same database for 2001-2018 by the University of California, Los Angeles (UCLA), suggesting that distant-stage cervical cancer (defined as disease that has spread to the bladder and/or rectum at diagnosis) is climbing 1.69% a year in White people versus 0.67% in Black individuals.
The UCLA researchers, headed by Alex Francoeur, MD, a resident in the department of obstetrics and gynecology, found that disparities were most stark in adenocarcinoma, with an annual increase of 3.40% a year among White women and 1.71% in Black women.
Such findings have equity researchers scratching their heads. In cancer, it’s rare to see evidence that Black patients are doing better than their White counterparts.
One theoretical explanation is that the data are flawed, Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society, told this news organization. For example, the UCLA analysis may have been fogged by changes in staging definitions over time, Dr. Jemal said, although this would not explain the racial disparities per se.
Dr. Deshmukh stands by his data and said that, for him, the message is clear: “If rising incidence is not for localized-stage disease, but for advanced stages, that means it’s attributable to lack of screening,” he told this news organization.
However, this ‘simple’ explanation generates even more questions, Dr. Deshmukh said: “Screening is not a one-time procedure [but] a spectrum of timely cervical precancer treatment if [required]. We don’t know when exactly non-Hispanic White women are falling behind on that spectrum.”
The UCLA study supports Dr. Deshmukh’s conclusions. Using data from the Behavioral Risk Factor Surveillance System to calculate trends in “nonguideline screening,” the researchers found that White women were almost twice as likely to report that they were not following screening guidelines compared with Black women over the period of 2001-2016 (26.6% vs. 13.8%; P < .001).
“It’s not an artifact, it’s real,” said Timothy Rebbeck, PhD, the Vincent L. Gregory Jr. Professor of Cancer Prevention at Harvard TH Chan School of Public Health, Boston, who was not an author of either study and was approached for comment.
“The data are correct but there are so many things going on that might explain these patterns,” he told this news organization.
“This is a great example of complex changes in our social system, political system, health care system that are having really clear, measurable effects,” Dr. Rebbeck said. “Cervical cancer is almost a canary in the coal mine for some of this because it’s so preventable.”
(The saying “canary in a coal mine” is a warning of danger or trouble ahead. It comes from the time when coal miners would carry a caged canary down into the tunnels to warn them of noxious gases, which would kill the bird but give men time to escape.)
For example, Dr. Rebbeck said, recent turmoil in U.S. health care has left many people distrustful of the system. Although he acknowledged this was “high speculation,” he suggested that some women may have become less willing to participate in any mass health care intervention because of their political beliefs.
The UCLA study found that distant cervical cancer was rising fastest in middle-aged White women in the U.S. South, at a rate of 4.5% per year (P < .001).
Dr. Rebbeck also suggested that Medicaid expansion – the broadening of health insurance coverage in some states since the Affordable Care Act in 2014 – could be implicated. Of the 11 states that have not yet expanded Medicaid, eight are in the South.
“White populations who are in states that didn’t expand Medicaid are not getting a lot of the standard treatment and care that you would expect ...” Dr. Rebbeck said. “You could very well imagine that Medicaid nonexpanding states would have all kinds of patterns that would lead to more aggressive disease.”
In fact, there is already evidence that Medicaid expansion has affected racial disparities, disproportionately benefiting Black and Hispanic families, as for example, from an analysis of 65 studies by the Kaiser Family Foundation in 2020.
Commenting on these data, Dr. Rebbeck said, “Does that mean that the patterns of advanced cervical cancer had a smaller effect on Black women in this period because there was a greater shift in access to care? This is again a speculation, but it does fit with the ‘canary in a coal mine’ concept that advanced cervical cancer may be more rapidly influenced by health care access than other health conditions.”
The authors of the UCLA study suggested another explanation for their results: Differing enthusiasm for human papillomavirus (HPV) vaccination among White and Black families. The team also analyzed data on HPV vaccination, which offers protection against cervical cancer. The researchers found that vaccination rates were lowest, at 66.1%, among White teenagers aged 13-17 years, compared with Hispanics at 75.3%, Black teenagers at 74.6%, and Asians at 68.1%.
However, this theory was dismissed by both Dr. Jemal and Dr. Rebbeck due to timing. HPV vaccines have been around for approximately 15 years, so women who benefited (or didn’t benefit) from vaccination would be only in their late 20s today, they pointed out.
“Ninety-five percent of the cervical cancer cases we see now are in women who have not been vaccinated,” said Dr. Jemal, “So that’s out of the equation.”
Dr. Rebbeck agreed: “HPV may or may not be a thing here because it’s [got] such a latency.”
HPV vaccination may be out of the picture, but what about the epidemiology of HPV itself? Could the virus directly or indirectly be boosting advanced cervical cancer in White women?
Dr. Deshmukh thinks that it might be doing so.
He published an analysis of 2000-2018 SEER data showing that U.S. counties with the highest incidences of HPV-associated cancers also had the highest levels of smoking.
Other recent data suggest that middle-aged White women in the United States are more likely to reach for a smoke than are Black women.
Dr. Deshmukh acknowledges that the link is speculative but reasonable: “We don’t know exactly what the impact of smoking would be in terms of ... the ability to clear HPV infection. It may inhibit apoptosis, promoting tumor growth. There’s no causal association. It’s a cofactor risk.”
Dr. Rebbeck is also suspicious that smoking patterns might be a factor, pointing out that “smoking is certainly associated with both health behaviors and advanced cervical cancer.”
Both Dr. Rebbeck and Dr. Deshmukh concluded that, at this point, we can only speculate on what’s driving the puzzling acceleration of cervical cancer in White women in the United States.
However, whether it’s political aversion to screening, smoking-boosted HPV infection, Medicaid expansion or lack of it, or something else, they all agree that this canary in the coal mine clearly needs urgent medical attention.
Dr. Rebbeck and Dr. Jemal have declared no conflicts of interest. Dr. Deshmukh has declared consultant or advisory roles for Merck and Value Analytics Labs. None of the authors of the UCLA study have declared competing interests.
A version of this article first appeared on Medscape.com.
Cervical cancer appears to be rising more rapidly in White women than in Black women in the United States, according to two independent studies. Researchers puzzling over this counterintuitive finding say that, if true, the findings may be a “canary in the coal mine,” signaling problems with U.S. health care that go way beyond women’s health.
Cervical cancer incidence in the United States has plateaued since 2010 and now stands at 7.5 per 100,000 people. Well-known disparities exist: Compared with White women, Black women are more likely to have distant-stage disease at diagnosis and more commonly die of their cancer.
However, two unconnected studies published in the past 5 months suggest that White women are catching up fast.
Cervical cancer rates in White women aged 30-34 are rising 2.8% a year, but holding steady for Black women, according to a recent study led by Ashish A. Deshmukh, PhD, of the Medical University of South Carolina, Charleston. His team analyzed the 2001-2019 National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) dataset, which covers 98% of the U.S. population and 227,062 cervical cancer cases.
These findings were echoed by an analysis of the same database for 2001-2018 by the University of California, Los Angeles (UCLA), suggesting that distant-stage cervical cancer (defined as disease that has spread to the bladder and/or rectum at diagnosis) is climbing 1.69% a year in White people versus 0.67% in Black individuals.
The UCLA researchers, headed by Alex Francoeur, MD, a resident in the department of obstetrics and gynecology, found that disparities were most stark in adenocarcinoma, with an annual increase of 3.40% a year among White women and 1.71% in Black women.
Such findings have equity researchers scratching their heads. In cancer, it’s rare to see evidence that Black patients are doing better than their White counterparts.
One theoretical explanation is that the data are flawed, Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society, told this news organization. For example, the UCLA analysis may have been fogged by changes in staging definitions over time, Dr. Jemal said, although this would not explain the racial disparities per se.
Dr. Deshmukh stands by his data and said that, for him, the message is clear: “If rising incidence is not for localized-stage disease, but for advanced stages, that means it’s attributable to lack of screening,” he told this news organization.
However, this ‘simple’ explanation generates even more questions, Dr. Deshmukh said: “Screening is not a one-time procedure [but] a spectrum of timely cervical precancer treatment if [required]. We don’t know when exactly non-Hispanic White women are falling behind on that spectrum.”
The UCLA study supports Dr. Deshmukh’s conclusions. Using data from the Behavioral Risk Factor Surveillance System to calculate trends in “nonguideline screening,” the researchers found that White women were almost twice as likely to report that they were not following screening guidelines compared with Black women over the period of 2001-2016 (26.6% vs. 13.8%; P < .001).
“It’s not an artifact, it’s real,” said Timothy Rebbeck, PhD, the Vincent L. Gregory Jr. Professor of Cancer Prevention at Harvard TH Chan School of Public Health, Boston, who was not an author of either study and was approached for comment.
“The data are correct but there are so many things going on that might explain these patterns,” he told this news organization.
“This is a great example of complex changes in our social system, political system, health care system that are having really clear, measurable effects,” Dr. Rebbeck said. “Cervical cancer is almost a canary in the coal mine for some of this because it’s so preventable.”
(The saying “canary in a coal mine” is a warning of danger or trouble ahead. It comes from the time when coal miners would carry a caged canary down into the tunnels to warn them of noxious gases, which would kill the bird but give men time to escape.)
For example, Dr. Rebbeck said, recent turmoil in U.S. health care has left many people distrustful of the system. Although he acknowledged this was “high speculation,” he suggested that some women may have become less willing to participate in any mass health care intervention because of their political beliefs.
The UCLA study found that distant cervical cancer was rising fastest in middle-aged White women in the U.S. South, at a rate of 4.5% per year (P < .001).
Dr. Rebbeck also suggested that Medicaid expansion – the broadening of health insurance coverage in some states since the Affordable Care Act in 2014 – could be implicated. Of the 11 states that have not yet expanded Medicaid, eight are in the South.
“White populations who are in states that didn’t expand Medicaid are not getting a lot of the standard treatment and care that you would expect ...” Dr. Rebbeck said. “You could very well imagine that Medicaid nonexpanding states would have all kinds of patterns that would lead to more aggressive disease.”
In fact, there is already evidence that Medicaid expansion has affected racial disparities, disproportionately benefiting Black and Hispanic families, as for example, from an analysis of 65 studies by the Kaiser Family Foundation in 2020.
Commenting on these data, Dr. Rebbeck said, “Does that mean that the patterns of advanced cervical cancer had a smaller effect on Black women in this period because there was a greater shift in access to care? This is again a speculation, but it does fit with the ‘canary in a coal mine’ concept that advanced cervical cancer may be more rapidly influenced by health care access than other health conditions.”
The authors of the UCLA study suggested another explanation for their results: Differing enthusiasm for human papillomavirus (HPV) vaccination among White and Black families. The team also analyzed data on HPV vaccination, which offers protection against cervical cancer. The researchers found that vaccination rates were lowest, at 66.1%, among White teenagers aged 13-17 years, compared with Hispanics at 75.3%, Black teenagers at 74.6%, and Asians at 68.1%.
However, this theory was dismissed by both Dr. Jemal and Dr. Rebbeck due to timing. HPV vaccines have been around for approximately 15 years, so women who benefited (or didn’t benefit) from vaccination would be only in their late 20s today, they pointed out.
“Ninety-five percent of the cervical cancer cases we see now are in women who have not been vaccinated,” said Dr. Jemal, “So that’s out of the equation.”
Dr. Rebbeck agreed: “HPV may or may not be a thing here because it’s [got] such a latency.”
HPV vaccination may be out of the picture, but what about the epidemiology of HPV itself? Could the virus directly or indirectly be boosting advanced cervical cancer in White women?
Dr. Deshmukh thinks that it might be doing so.
He published an analysis of 2000-2018 SEER data showing that U.S. counties with the highest incidences of HPV-associated cancers also had the highest levels of smoking.
Other recent data suggest that middle-aged White women in the United States are more likely to reach for a smoke than are Black women.
Dr. Deshmukh acknowledges that the link is speculative but reasonable: “We don’t know exactly what the impact of smoking would be in terms of ... the ability to clear HPV infection. It may inhibit apoptosis, promoting tumor growth. There’s no causal association. It’s a cofactor risk.”
Dr. Rebbeck is also suspicious that smoking patterns might be a factor, pointing out that “smoking is certainly associated with both health behaviors and advanced cervical cancer.”
Both Dr. Rebbeck and Dr. Deshmukh concluded that, at this point, we can only speculate on what’s driving the puzzling acceleration of cervical cancer in White women in the United States.
However, whether it’s political aversion to screening, smoking-boosted HPV infection, Medicaid expansion or lack of it, or something else, they all agree that this canary in the coal mine clearly needs urgent medical attention.
Dr. Rebbeck and Dr. Jemal have declared no conflicts of interest. Dr. Deshmukh has declared consultant or advisory roles for Merck and Value Analytics Labs. None of the authors of the UCLA study have declared competing interests.
A version of this article first appeared on Medscape.com.