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Rheumatoid arthritis linked to increased Parkinson’s risk
Claims data in 55,000 patients with RA and 273,000 age- and sex-matched controls show that those with RA were 1.74 times more likely than controls to be diagnosed with PD.
“If patients with rheumatoid arthritis begin exhibiting motor symptoms such as muscle rigidity, tremors, or slowed movement, it is imperative that they be evaluated by a qualified neurologist to rule out the possibility of developing Parkinson’s disease,” study investigator Hyungjin Kim, MD, PhD, told this news organization.
Dr. Kim is an associate professor in the department of medical humanities at Sungkyunkwan University School of Medicine in Seoul, South Korea.
The findings were published online in JAMA Neurology.
Conflicting findings
The investigators note that a number of studies have examined the link between RA and PD, with conflicting results – one even showing a 35% reduced risk for PD for individuals with RA. A more recent population-based study in Taiwan showed a 37% higher rate of PD in patients with rheumatic disease.
However, previous studies did not control for important variables such as body mass index or diabetes.
For the current study, the investigators analyzed claims on about 55,000 patients diagnosed with RA between 2010 and 2017, with follow-up until 2019, and compared the outcomes of this group vs. those of 273,000 controls.
The mean age of claimants was 58 years, and 75% were female.
Results showed that those diagnosed with seropositive RA were about twice as likely as controls to be diagnosed with PD. Those with seronegative RA were 1.2 times as likely as controls to be diagnosed with PD.
Dr. Kim noted that although the pathogenic link between RA and PD remains elusive, inflammation probably plays an important role. “Inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, which are increased in RA patients, can induce microglial activation, leading to neuroinflammation,” he stated.
“These inflammatory cytokines are known to be associated with the dysfunction and degeneration of nigral dopaminergic neurons, which are important in the pathogenesis of PD,” he added.
The investigators noted that patients with RA may have been subject to more frequent health care services than controls and so were more likely to obtain a PD diagnosis.
Another possibility was that because patients with health check-ups were included in the analysis, the findings may have been biased toward those who were older and who had a higher income.
Dr. Kim noted that additional research is required to clarify the pathogenic connection between RA and PD.
“Moreover, additional studies are necessary to explore the potential influence of novel therapeutic treatments for RA on Parkinson’s disease susceptibility in patients with RA,” he said.
Commenting on the findings for this news organization, David Sulzer, PhD, professor of psychiatry, neurology, and pharmacology at Columbia University in New York, said that the study adds to the growing body of evidence showing there is an autoimmune component to PD.
Dr. Sulzer pointed to data in several papers he published with others to this effect, including one showing higher rates of PD in people with inflammatory bowel disease.
The study had no specific funding. The study investigators and Dr. Sulzer report no relevant disclosures.
A version of this article first appeared on Medscape.com.
Claims data in 55,000 patients with RA and 273,000 age- and sex-matched controls show that those with RA were 1.74 times more likely than controls to be diagnosed with PD.
“If patients with rheumatoid arthritis begin exhibiting motor symptoms such as muscle rigidity, tremors, or slowed movement, it is imperative that they be evaluated by a qualified neurologist to rule out the possibility of developing Parkinson’s disease,” study investigator Hyungjin Kim, MD, PhD, told this news organization.
Dr. Kim is an associate professor in the department of medical humanities at Sungkyunkwan University School of Medicine in Seoul, South Korea.
The findings were published online in JAMA Neurology.
Conflicting findings
The investigators note that a number of studies have examined the link between RA and PD, with conflicting results – one even showing a 35% reduced risk for PD for individuals with RA. A more recent population-based study in Taiwan showed a 37% higher rate of PD in patients with rheumatic disease.
However, previous studies did not control for important variables such as body mass index or diabetes.
For the current study, the investigators analyzed claims on about 55,000 patients diagnosed with RA between 2010 and 2017, with follow-up until 2019, and compared the outcomes of this group vs. those of 273,000 controls.
The mean age of claimants was 58 years, and 75% were female.
Results showed that those diagnosed with seropositive RA were about twice as likely as controls to be diagnosed with PD. Those with seronegative RA were 1.2 times as likely as controls to be diagnosed with PD.
Dr. Kim noted that although the pathogenic link between RA and PD remains elusive, inflammation probably plays an important role. “Inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, which are increased in RA patients, can induce microglial activation, leading to neuroinflammation,” he stated.
“These inflammatory cytokines are known to be associated with the dysfunction and degeneration of nigral dopaminergic neurons, which are important in the pathogenesis of PD,” he added.
The investigators noted that patients with RA may have been subject to more frequent health care services than controls and so were more likely to obtain a PD diagnosis.
Another possibility was that because patients with health check-ups were included in the analysis, the findings may have been biased toward those who were older and who had a higher income.
Dr. Kim noted that additional research is required to clarify the pathogenic connection between RA and PD.
“Moreover, additional studies are necessary to explore the potential influence of novel therapeutic treatments for RA on Parkinson’s disease susceptibility in patients with RA,” he said.
Commenting on the findings for this news organization, David Sulzer, PhD, professor of psychiatry, neurology, and pharmacology at Columbia University in New York, said that the study adds to the growing body of evidence showing there is an autoimmune component to PD.
Dr. Sulzer pointed to data in several papers he published with others to this effect, including one showing higher rates of PD in people with inflammatory bowel disease.
The study had no specific funding. The study investigators and Dr. Sulzer report no relevant disclosures.
A version of this article first appeared on Medscape.com.
Claims data in 55,000 patients with RA and 273,000 age- and sex-matched controls show that those with RA were 1.74 times more likely than controls to be diagnosed with PD.
“If patients with rheumatoid arthritis begin exhibiting motor symptoms such as muscle rigidity, tremors, or slowed movement, it is imperative that they be evaluated by a qualified neurologist to rule out the possibility of developing Parkinson’s disease,” study investigator Hyungjin Kim, MD, PhD, told this news organization.
Dr. Kim is an associate professor in the department of medical humanities at Sungkyunkwan University School of Medicine in Seoul, South Korea.
The findings were published online in JAMA Neurology.
Conflicting findings
The investigators note that a number of studies have examined the link between RA and PD, with conflicting results – one even showing a 35% reduced risk for PD for individuals with RA. A more recent population-based study in Taiwan showed a 37% higher rate of PD in patients with rheumatic disease.
However, previous studies did not control for important variables such as body mass index or diabetes.
For the current study, the investigators analyzed claims on about 55,000 patients diagnosed with RA between 2010 and 2017, with follow-up until 2019, and compared the outcomes of this group vs. those of 273,000 controls.
The mean age of claimants was 58 years, and 75% were female.
Results showed that those diagnosed with seropositive RA were about twice as likely as controls to be diagnosed with PD. Those with seronegative RA were 1.2 times as likely as controls to be diagnosed with PD.
Dr. Kim noted that although the pathogenic link between RA and PD remains elusive, inflammation probably plays an important role. “Inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, which are increased in RA patients, can induce microglial activation, leading to neuroinflammation,” he stated.
“These inflammatory cytokines are known to be associated with the dysfunction and degeneration of nigral dopaminergic neurons, which are important in the pathogenesis of PD,” he added.
The investigators noted that patients with RA may have been subject to more frequent health care services than controls and so were more likely to obtain a PD diagnosis.
Another possibility was that because patients with health check-ups were included in the analysis, the findings may have been biased toward those who were older and who had a higher income.
Dr. Kim noted that additional research is required to clarify the pathogenic connection between RA and PD.
“Moreover, additional studies are necessary to explore the potential influence of novel therapeutic treatments for RA on Parkinson’s disease susceptibility in patients with RA,” he said.
Commenting on the findings for this news organization, David Sulzer, PhD, professor of psychiatry, neurology, and pharmacology at Columbia University in New York, said that the study adds to the growing body of evidence showing there is an autoimmune component to PD.
Dr. Sulzer pointed to data in several papers he published with others to this effect, including one showing higher rates of PD in people with inflammatory bowel disease.
The study had no specific funding. The study investigators and Dr. Sulzer report no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
Normal CRP during RA flares: An ‘underappreciated, persistent phenotype’
MANCHESTER, England – Even when C-reactive protein (CRP) levels are normal, patients with seropositive rheumatoid arthritis (RA) could still be experiencing significant disease that persists over time, researchers from University College London have found.
Similar levels of joint erosion and disease activity were observed over a 5-year period; researchers compared patients who had high CRP levels (> 5 mg/L)* with patients whose CRP levels were consistently normal (< 5 mg/L) at the time of an ultrasound-proven disease flare.
“Our data suggests that the phenotype of normal CRP represents at least 5% of our cohort,” Bhavika Sethi, MBChB, reported in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.
“They are more likely to require biologic treatment, and this continues on even though they have equivalent DAS28 [disease activity score in 28 joints] and risk of joint damage” to high-CRP patients, she said.
These patients are a significant minority, Dr. Sethi added, and “we need to think about how we provide care for them and allocate resources.”
Diagnostic delay and poor outcomes previously seen
The study is a continuation of a larger project, the corresponding author for the poster, Matthew Hutchinson, MBChB, told this news organization.
A few years ago, Dr. Hutchinson explained, a subset of patients with normal CRP levels during RA flares were identified and were found to be more likely to have experienced diagnostic delay and worse outcomes than did those with high CRP levels.
The aim of the current study was to see whether those findings persisted by longitudinally assessing patient records and seeing what happened 1, 2, and 5 years later. They evaluated 312 patients with seropositive RA, of whom 28 had CRP < 5 mg/L as well as active disease, which was determined on the basis of a DAS28 > 4.5. Of those 28 patients, 16 had persistently low CRP (< 5 mg/L) despite active disease. All patients who were taking tocilizumab were excluded from the study because of its CRP-lowering properties.
“Our project was showing that this group of people exist, trying to characterize them a little better” and that the study serves as a “jumping-off point” for future research, Dr. Hutchinson said.
The study was also conducted to “make people more aware of [patients with normal CRP during flare], because treating clinicians could be falsely reassured by a normal CRP,” he added. “Patients in front of them could actually be undertreated and have worse outcomes if [it is] not picked up,” Dr. Hutchinson suggested.
In comparison with those with high CRP levels, those with normal CRP levels were more likely to be receiving biologic treatment at 5 years (76.6% vs. 44.4%; P = .0323).
At 5 years, DAS28 was similar (P = .9615) among patients with normal CRP levels and those with high CRP levels, at a median of 2.8 and 3.2, respectively. A similar percentage of patients in these two groups also had joint damage (63.3% vs. 71.4%; P = .7384).
Don’t rely only on CRP to diagnose and manage RA flares
“CRP is a generic inflammatory marker in most people,” Dr. Hutchinson said. “In the majority of situations when either there is inflammation or an infection, certainly if it’s systemic infection or inflammation, you will find CRP being elevated on the blood tests.”
For someone presenting with joint pain, high CRP can be a useful indicator that it’s more of an inflammatory process than physical injury, he added. CRP is also frequently used to calculate DAS28 to monitor disease activity.
“This study highlights that CRP may be normal during flares in some people with RA,” Jeffrey A. Sparks, MD, told this news organization.
“These patients may still require advanced therapies and can accrue damage,” the rheumatologist from Brigham and Women’s Hospital and Harvard University, Boston, added.
“Clinicians should not only rely on CRP to diagnose and manage RA flares,” said Dr. Sparks, who was not involved in the study.
The study was independently supported. Dr. Hutchinson and Dr. Sethi report no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care; he has received research support from Bristol-Myers Squibb and has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.
*Correction, 5/9/2023: This article has been updated to correct the units for C-reactive protein from mg/dL to mg/L.
A version of this article first appeared on Medscape.com.
MANCHESTER, England – Even when C-reactive protein (CRP) levels are normal, patients with seropositive rheumatoid arthritis (RA) could still be experiencing significant disease that persists over time, researchers from University College London have found.
Similar levels of joint erosion and disease activity were observed over a 5-year period; researchers compared patients who had high CRP levels (> 5 mg/L)* with patients whose CRP levels were consistently normal (< 5 mg/L) at the time of an ultrasound-proven disease flare.
“Our data suggests that the phenotype of normal CRP represents at least 5% of our cohort,” Bhavika Sethi, MBChB, reported in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.
“They are more likely to require biologic treatment, and this continues on even though they have equivalent DAS28 [disease activity score in 28 joints] and risk of joint damage” to high-CRP patients, she said.
These patients are a significant minority, Dr. Sethi added, and “we need to think about how we provide care for them and allocate resources.”
Diagnostic delay and poor outcomes previously seen
The study is a continuation of a larger project, the corresponding author for the poster, Matthew Hutchinson, MBChB, told this news organization.
A few years ago, Dr. Hutchinson explained, a subset of patients with normal CRP levels during RA flares were identified and were found to be more likely to have experienced diagnostic delay and worse outcomes than did those with high CRP levels.
The aim of the current study was to see whether those findings persisted by longitudinally assessing patient records and seeing what happened 1, 2, and 5 years later. They evaluated 312 patients with seropositive RA, of whom 28 had CRP < 5 mg/L as well as active disease, which was determined on the basis of a DAS28 > 4.5. Of those 28 patients, 16 had persistently low CRP (< 5 mg/L) despite active disease. All patients who were taking tocilizumab were excluded from the study because of its CRP-lowering properties.
“Our project was showing that this group of people exist, trying to characterize them a little better” and that the study serves as a “jumping-off point” for future research, Dr. Hutchinson said.
The study was also conducted to “make people more aware of [patients with normal CRP during flare], because treating clinicians could be falsely reassured by a normal CRP,” he added. “Patients in front of them could actually be undertreated and have worse outcomes if [it is] not picked up,” Dr. Hutchinson suggested.
In comparison with those with high CRP levels, those with normal CRP levels were more likely to be receiving biologic treatment at 5 years (76.6% vs. 44.4%; P = .0323).
At 5 years, DAS28 was similar (P = .9615) among patients with normal CRP levels and those with high CRP levels, at a median of 2.8 and 3.2, respectively. A similar percentage of patients in these two groups also had joint damage (63.3% vs. 71.4%; P = .7384).
Don’t rely only on CRP to diagnose and manage RA flares
“CRP is a generic inflammatory marker in most people,” Dr. Hutchinson said. “In the majority of situations when either there is inflammation or an infection, certainly if it’s systemic infection or inflammation, you will find CRP being elevated on the blood tests.”
For someone presenting with joint pain, high CRP can be a useful indicator that it’s more of an inflammatory process than physical injury, he added. CRP is also frequently used to calculate DAS28 to monitor disease activity.
“This study highlights that CRP may be normal during flares in some people with RA,” Jeffrey A. Sparks, MD, told this news organization.
“These patients may still require advanced therapies and can accrue damage,” the rheumatologist from Brigham and Women’s Hospital and Harvard University, Boston, added.
“Clinicians should not only rely on CRP to diagnose and manage RA flares,” said Dr. Sparks, who was not involved in the study.
The study was independently supported. Dr. Hutchinson and Dr. Sethi report no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care; he has received research support from Bristol-Myers Squibb and has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.
*Correction, 5/9/2023: This article has been updated to correct the units for C-reactive protein from mg/dL to mg/L.
A version of this article first appeared on Medscape.com.
MANCHESTER, England – Even when C-reactive protein (CRP) levels are normal, patients with seropositive rheumatoid arthritis (RA) could still be experiencing significant disease that persists over time, researchers from University College London have found.
Similar levels of joint erosion and disease activity were observed over a 5-year period; researchers compared patients who had high CRP levels (> 5 mg/L)* with patients whose CRP levels were consistently normal (< 5 mg/L) at the time of an ultrasound-proven disease flare.
“Our data suggests that the phenotype of normal CRP represents at least 5% of our cohort,” Bhavika Sethi, MBChB, reported in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.
“They are more likely to require biologic treatment, and this continues on even though they have equivalent DAS28 [disease activity score in 28 joints] and risk of joint damage” to high-CRP patients, she said.
These patients are a significant minority, Dr. Sethi added, and “we need to think about how we provide care for them and allocate resources.”
Diagnostic delay and poor outcomes previously seen
The study is a continuation of a larger project, the corresponding author for the poster, Matthew Hutchinson, MBChB, told this news organization.
A few years ago, Dr. Hutchinson explained, a subset of patients with normal CRP levels during RA flares were identified and were found to be more likely to have experienced diagnostic delay and worse outcomes than did those with high CRP levels.
The aim of the current study was to see whether those findings persisted by longitudinally assessing patient records and seeing what happened 1, 2, and 5 years later. They evaluated 312 patients with seropositive RA, of whom 28 had CRP < 5 mg/L as well as active disease, which was determined on the basis of a DAS28 > 4.5. Of those 28 patients, 16 had persistently low CRP (< 5 mg/L) despite active disease. All patients who were taking tocilizumab were excluded from the study because of its CRP-lowering properties.
“Our project was showing that this group of people exist, trying to characterize them a little better” and that the study serves as a “jumping-off point” for future research, Dr. Hutchinson said.
The study was also conducted to “make people more aware of [patients with normal CRP during flare], because treating clinicians could be falsely reassured by a normal CRP,” he added. “Patients in front of them could actually be undertreated and have worse outcomes if [it is] not picked up,” Dr. Hutchinson suggested.
In comparison with those with high CRP levels, those with normal CRP levels were more likely to be receiving biologic treatment at 5 years (76.6% vs. 44.4%; P = .0323).
At 5 years, DAS28 was similar (P = .9615) among patients with normal CRP levels and those with high CRP levels, at a median of 2.8 and 3.2, respectively. A similar percentage of patients in these two groups also had joint damage (63.3% vs. 71.4%; P = .7384).
Don’t rely only on CRP to diagnose and manage RA flares
“CRP is a generic inflammatory marker in most people,” Dr. Hutchinson said. “In the majority of situations when either there is inflammation or an infection, certainly if it’s systemic infection or inflammation, you will find CRP being elevated on the blood tests.”
For someone presenting with joint pain, high CRP can be a useful indicator that it’s more of an inflammatory process than physical injury, he added. CRP is also frequently used to calculate DAS28 to monitor disease activity.
“This study highlights that CRP may be normal during flares in some people with RA,” Jeffrey A. Sparks, MD, told this news organization.
“These patients may still require advanced therapies and can accrue damage,” the rheumatologist from Brigham and Women’s Hospital and Harvard University, Boston, added.
“Clinicians should not only rely on CRP to diagnose and manage RA flares,” said Dr. Sparks, who was not involved in the study.
The study was independently supported. Dr. Hutchinson and Dr. Sethi report no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care; he has received research support from Bristol-Myers Squibb and has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.
*Correction, 5/9/2023: This article has been updated to correct the units for C-reactive protein from mg/dL to mg/L.
A version of this article first appeared on Medscape.com.
AT BSR 2023
FDA puts partial hold on investigational alopecia areata drug deuruxolitinib
The in a press release on May 2.
The announcement came after a pulmonary embolism occurred with the 12-mg twice-daily dose in one of the long-term open-label extension (OLE) studies, the company, Sun Pharmaceutical Industries, said.
The company stated that the FDA has placed the Investigational New Drug testing for deuruxolitinib on partial clinical hold, and the agency is requiring that study participants who are currently on the 12-mg twice-daily dose in the OLE studies stop taking that dose. The hold covers only the 12-mg dose.
No hold on 8-mg dose
“There have been no thrombotic events reported to date for the 8-mg b.i.d. dose and U.S. FDA has not placed the 8-mg b.i.d. dose on hold,” the company said in the statement.
The statement added, “We are taking immediate steps to transition the patients in the OLE studies to the 8-mg b.i.d. dose arm in the ongoing studies.”
The company said that no thromboembolic events were observed in the phase 2 or phase 3 trials and said that it will work closely with the FDA to address its concerns. A formal letter detailing the FDA’s concerns is expected within 30 days.
Deuruxolitinib is an investigational oral selective inhibitor of Janus kinase 1 (JAK1) and JAK2 enzymes.
The FDA has granted deuruxolitinib breakthrough therapy designation for the treatment of adult patients with moderate to severe alopecia areata as well as fast-track designation for the treatment of alopecia areata.
In March, this news organization reported from the annual meeting of the American Academy of Dermatology that, based on phase 3 studies that demonstrate robust hair growth in about one-third of patients, deuruxolitinib has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received FDA approval almost 1 year ago.
Also at the AAD annual meeting, this news organization reported that principal investigator Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., in his presentation on the results of THRIVE-AA2, one of the two phase 3 trials of deuruxolitinib, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.” Dr King also was a principal investigator in studies of baricitinib.
With one exception, labeling for baricitinib and other JAK inhibitors with dermatologic indications includes a boxed warning listing serious adverse events including the risk for major adverse cardiac events and thrombosis, including pulmonary embolism, based on the risks in a rheumatoid arthritis study.
A version of this article first appeared on Medscape.com.
The in a press release on May 2.
The announcement came after a pulmonary embolism occurred with the 12-mg twice-daily dose in one of the long-term open-label extension (OLE) studies, the company, Sun Pharmaceutical Industries, said.
The company stated that the FDA has placed the Investigational New Drug testing for deuruxolitinib on partial clinical hold, and the agency is requiring that study participants who are currently on the 12-mg twice-daily dose in the OLE studies stop taking that dose. The hold covers only the 12-mg dose.
No hold on 8-mg dose
“There have been no thrombotic events reported to date for the 8-mg b.i.d. dose and U.S. FDA has not placed the 8-mg b.i.d. dose on hold,” the company said in the statement.
The statement added, “We are taking immediate steps to transition the patients in the OLE studies to the 8-mg b.i.d. dose arm in the ongoing studies.”
The company said that no thromboembolic events were observed in the phase 2 or phase 3 trials and said that it will work closely with the FDA to address its concerns. A formal letter detailing the FDA’s concerns is expected within 30 days.
Deuruxolitinib is an investigational oral selective inhibitor of Janus kinase 1 (JAK1) and JAK2 enzymes.
The FDA has granted deuruxolitinib breakthrough therapy designation for the treatment of adult patients with moderate to severe alopecia areata as well as fast-track designation for the treatment of alopecia areata.
In March, this news organization reported from the annual meeting of the American Academy of Dermatology that, based on phase 3 studies that demonstrate robust hair growth in about one-third of patients, deuruxolitinib has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received FDA approval almost 1 year ago.
Also at the AAD annual meeting, this news organization reported that principal investigator Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., in his presentation on the results of THRIVE-AA2, one of the two phase 3 trials of deuruxolitinib, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.” Dr King also was a principal investigator in studies of baricitinib.
With one exception, labeling for baricitinib and other JAK inhibitors with dermatologic indications includes a boxed warning listing serious adverse events including the risk for major adverse cardiac events and thrombosis, including pulmonary embolism, based on the risks in a rheumatoid arthritis study.
A version of this article first appeared on Medscape.com.
The in a press release on May 2.
The announcement came after a pulmonary embolism occurred with the 12-mg twice-daily dose in one of the long-term open-label extension (OLE) studies, the company, Sun Pharmaceutical Industries, said.
The company stated that the FDA has placed the Investigational New Drug testing for deuruxolitinib on partial clinical hold, and the agency is requiring that study participants who are currently on the 12-mg twice-daily dose in the OLE studies stop taking that dose. The hold covers only the 12-mg dose.
No hold on 8-mg dose
“There have been no thrombotic events reported to date for the 8-mg b.i.d. dose and U.S. FDA has not placed the 8-mg b.i.d. dose on hold,” the company said in the statement.
The statement added, “We are taking immediate steps to transition the patients in the OLE studies to the 8-mg b.i.d. dose arm in the ongoing studies.”
The company said that no thromboembolic events were observed in the phase 2 or phase 3 trials and said that it will work closely with the FDA to address its concerns. A formal letter detailing the FDA’s concerns is expected within 30 days.
Deuruxolitinib is an investigational oral selective inhibitor of Janus kinase 1 (JAK1) and JAK2 enzymes.
The FDA has granted deuruxolitinib breakthrough therapy designation for the treatment of adult patients with moderate to severe alopecia areata as well as fast-track designation for the treatment of alopecia areata.
In March, this news organization reported from the annual meeting of the American Academy of Dermatology that, based on phase 3 studies that demonstrate robust hair growth in about one-third of patients, deuruxolitinib has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received FDA approval almost 1 year ago.
Also at the AAD annual meeting, this news organization reported that principal investigator Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., in his presentation on the results of THRIVE-AA2, one of the two phase 3 trials of deuruxolitinib, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.” Dr King also was a principal investigator in studies of baricitinib.
With one exception, labeling for baricitinib and other JAK inhibitors with dermatologic indications includes a boxed warning listing serious adverse events including the risk for major adverse cardiac events and thrombosis, including pulmonary embolism, based on the risks in a rheumatoid arthritis study.
A version of this article first appeared on Medscape.com.
Researchers seek to understand post-COVID autoimmune disease risk
Since the COVID-19 pandemic started more than 3 years ago, the longer-lasting effects of SARS-CoV-2 infection have continued to reveal themselves. Approximately 28% of Americans report having ever experienced post-COVID conditions, such as brain fog, postexertional malaise, and joint pain, and 11% say they are still experiencing these long-term effects. Now, new research is showing that people who have had COVID are more likely to newly develop an autoimmune disease. Exactly why this is happening is less clear, experts say.
Two preprint studies and one study published in a peer-reviewed journal provide strong evidence that patients who have been infected with SARS-CoV-2 are at elevated risk of developing an autoimmune disease. The studies retrospectively reviewed medical records from three countries and compared the incidence of new-onset autoimmune disease among patients who had polymerase chain reaction–confirmed COVID-19 and those who had never been diagnosed with the virus.
A study analyzing the health records of 3.8 million U.S. patients – more than 888,460 with confirmed COVID-19 – found that the COVID-19 group was two to three times as likely to develop various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. A U.K. preprint study that included more than 458,000 people with confirmed COVID found that those who had previously been infected with SARS-CoV-2 were 22% more likely to develop an autoimmune disease compared with the control group. In this cohort, the diseases most strongly associated with COVID-19 were type 1 diabetes, inflammatory bowel disease, and psoriasis. A preprint study from German researchers found that COVID-19 patients were almost 43% more likely to develop an autoimmune disease, compared with those who had never been infected. COVID-19 was most strongly linked to vasculitis.
These large studies are telling us, “Yes, this link is there, so we have to accept it,” Sonia Sharma, PhD, of the Center for Autoimmunity and Inflammation at the La Jolla (Calif.) Institute for Immunology, told this news organization. But this is not the first time that autoimmune diseases have been linked to previous infections.
Researchers have known for decades that Epstein-Barr virus infection is linked to several autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. More recent research suggests the virus may activate certain genes associated with these immune disorders. Hepatitis C virus can induce cryoglobulinemia, and infection with cytomegalovirus has been implicated in several autoimmune diseases. Bacterial infections have also been linked to autoimmunity, such as group A streptococcus and rheumatic fever, as well as salmonella and reactive arthritis, to name only a few.
“In a way, this isn’t necessarily a new concept to physicians, particularly rheumatologists,” said Jeffrey A. Sparks, MD, a rheumatologist at Brigham and Women’s Hospital in Boston. “There’s a fine line between appropriately clearing an infection and the body overreacting and setting off a cascade where the immune system is chronically overactive that can manifest as an autoimmune disease,” he told this news organization.
A dysregulated response to infection
It takes the immune system a week or two to develop antigen-specific antibodies to a new pathogen. But for patients with serious infections – in this instance, COVID-19 – that’s time they don’t have. Therefore, the immune system has an alternative pathway, called extrafollicular activation, that creates fast-acting antibodies, explained Matthew Woodruff, PhD, an instructor of immunology and rheumatology at Emory University, Atlanta.
The trade-off is that these antibodies are not as specific and can target the body’s own tissues. This dysregulation of antibody selection is generally short lived and fades when more targeted antibodies are produced and take over, but in some cases, this process can lead to high levels of self-targeting antibodies that can harm the body’s organs and tissues. Research also suggests that for patients who experience long COVID, the same autoantibodies that drive the initial immune response are detectable in the body months after infection, though it is not known whether these lingering immune cells cause these longer-lasting symptoms.
“If you have a virus that causes hyperinflammation plus organ damage, that is a recipe for disaster,” Dr. Sharma said. “It’s a recipe for autoantibodies and autoreactive T cells that down the road can attack the body’s own tissues, especially in people whose immune system is trained in such a way to cause self-reactivity,” she added.
This hyperinflammation can result in rare but serious complications, such as multisystem inflammatory syndrome in children and adults, which can occur 2-6 weeks after SARS-CoV-2 infection. But even in these patients with severe illness, organ-specific complications tend to resolve in 6 months with “no significant sequelae 1 year after diagnosis,” according to the Centers for Disease Control and Prevention. And while long COVID can last for a year or longer, data suggest that symptoms do eventually resolve for most people. What is not clear is why acute autoimmunity triggered by COVID-19 can become a chronic condition in certain patients.
Predisposition to autoimmunity
P. J. Utz, MD, PhD, professor of immunology and rheumatology at Stanford (Calif.) University, said that people who develop autoimmune disease after SARS-CoV-2 infection may have already been predisposed toward autoimmunity. Especially for autoimmune diseases such as type 1 diabetes and lupus, autoantibodies can appear and circulate in the body for more than a decade in some people before they present with any clinical symptoms. “Their immune system is primed such that if they get infected with something – or they have some other environmental trigger that maybe we don’t know about yet – that is enough to then push them over the edge so that they get full-blown autoimmunity,” he said. What is not known is whether these patients’ conditions would have advanced to true clinical disease had they not been infected, he said.
He also noted that the presence of autoantibodies does not necessarily mean someone has autoimmune disease; healthy people can also have autoantibodies, and everyone develops them with age. “My advice would be, ‘Don’t lose sleep over this,’ “ he said.
Dr. Sparks agreed that while these retrospective studies did show an elevated risk of autoimmune disease after COVID-19, that risk appears to be relatively small. “As a practicing rheumatologist, we aren’t seeing a stampede of patients with new-onset rheumatic diseases,” he said. “It’s not like we’re overwhelmed with autoimmune patients, even though almost everyone’s had COVID. So, if there is a risk, it’s very modest.”
Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Utz receives research funding from Pfizer. Dr. Sharma and Dr. Woodruff have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Since the COVID-19 pandemic started more than 3 years ago, the longer-lasting effects of SARS-CoV-2 infection have continued to reveal themselves. Approximately 28% of Americans report having ever experienced post-COVID conditions, such as brain fog, postexertional malaise, and joint pain, and 11% say they are still experiencing these long-term effects. Now, new research is showing that people who have had COVID are more likely to newly develop an autoimmune disease. Exactly why this is happening is less clear, experts say.
Two preprint studies and one study published in a peer-reviewed journal provide strong evidence that patients who have been infected with SARS-CoV-2 are at elevated risk of developing an autoimmune disease. The studies retrospectively reviewed medical records from three countries and compared the incidence of new-onset autoimmune disease among patients who had polymerase chain reaction–confirmed COVID-19 and those who had never been diagnosed with the virus.
A study analyzing the health records of 3.8 million U.S. patients – more than 888,460 with confirmed COVID-19 – found that the COVID-19 group was two to three times as likely to develop various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. A U.K. preprint study that included more than 458,000 people with confirmed COVID found that those who had previously been infected with SARS-CoV-2 were 22% more likely to develop an autoimmune disease compared with the control group. In this cohort, the diseases most strongly associated with COVID-19 were type 1 diabetes, inflammatory bowel disease, and psoriasis. A preprint study from German researchers found that COVID-19 patients were almost 43% more likely to develop an autoimmune disease, compared with those who had never been infected. COVID-19 was most strongly linked to vasculitis.
These large studies are telling us, “Yes, this link is there, so we have to accept it,” Sonia Sharma, PhD, of the Center for Autoimmunity and Inflammation at the La Jolla (Calif.) Institute for Immunology, told this news organization. But this is not the first time that autoimmune diseases have been linked to previous infections.
Researchers have known for decades that Epstein-Barr virus infection is linked to several autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. More recent research suggests the virus may activate certain genes associated with these immune disorders. Hepatitis C virus can induce cryoglobulinemia, and infection with cytomegalovirus has been implicated in several autoimmune diseases. Bacterial infections have also been linked to autoimmunity, such as group A streptococcus and rheumatic fever, as well as salmonella and reactive arthritis, to name only a few.
“In a way, this isn’t necessarily a new concept to physicians, particularly rheumatologists,” said Jeffrey A. Sparks, MD, a rheumatologist at Brigham and Women’s Hospital in Boston. “There’s a fine line between appropriately clearing an infection and the body overreacting and setting off a cascade where the immune system is chronically overactive that can manifest as an autoimmune disease,” he told this news organization.
A dysregulated response to infection
It takes the immune system a week or two to develop antigen-specific antibodies to a new pathogen. But for patients with serious infections – in this instance, COVID-19 – that’s time they don’t have. Therefore, the immune system has an alternative pathway, called extrafollicular activation, that creates fast-acting antibodies, explained Matthew Woodruff, PhD, an instructor of immunology and rheumatology at Emory University, Atlanta.
The trade-off is that these antibodies are not as specific and can target the body’s own tissues. This dysregulation of antibody selection is generally short lived and fades when more targeted antibodies are produced and take over, but in some cases, this process can lead to high levels of self-targeting antibodies that can harm the body’s organs and tissues. Research also suggests that for patients who experience long COVID, the same autoantibodies that drive the initial immune response are detectable in the body months after infection, though it is not known whether these lingering immune cells cause these longer-lasting symptoms.
“If you have a virus that causes hyperinflammation plus organ damage, that is a recipe for disaster,” Dr. Sharma said. “It’s a recipe for autoantibodies and autoreactive T cells that down the road can attack the body’s own tissues, especially in people whose immune system is trained in such a way to cause self-reactivity,” she added.
This hyperinflammation can result in rare but serious complications, such as multisystem inflammatory syndrome in children and adults, which can occur 2-6 weeks after SARS-CoV-2 infection. But even in these patients with severe illness, organ-specific complications tend to resolve in 6 months with “no significant sequelae 1 year after diagnosis,” according to the Centers for Disease Control and Prevention. And while long COVID can last for a year or longer, data suggest that symptoms do eventually resolve for most people. What is not clear is why acute autoimmunity triggered by COVID-19 can become a chronic condition in certain patients.
Predisposition to autoimmunity
P. J. Utz, MD, PhD, professor of immunology and rheumatology at Stanford (Calif.) University, said that people who develop autoimmune disease after SARS-CoV-2 infection may have already been predisposed toward autoimmunity. Especially for autoimmune diseases such as type 1 diabetes and lupus, autoantibodies can appear and circulate in the body for more than a decade in some people before they present with any clinical symptoms. “Their immune system is primed such that if they get infected with something – or they have some other environmental trigger that maybe we don’t know about yet – that is enough to then push them over the edge so that they get full-blown autoimmunity,” he said. What is not known is whether these patients’ conditions would have advanced to true clinical disease had they not been infected, he said.
He also noted that the presence of autoantibodies does not necessarily mean someone has autoimmune disease; healthy people can also have autoantibodies, and everyone develops them with age. “My advice would be, ‘Don’t lose sleep over this,’ “ he said.
Dr. Sparks agreed that while these retrospective studies did show an elevated risk of autoimmune disease after COVID-19, that risk appears to be relatively small. “As a practicing rheumatologist, we aren’t seeing a stampede of patients with new-onset rheumatic diseases,” he said. “It’s not like we’re overwhelmed with autoimmune patients, even though almost everyone’s had COVID. So, if there is a risk, it’s very modest.”
Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Utz receives research funding from Pfizer. Dr. Sharma and Dr. Woodruff have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Since the COVID-19 pandemic started more than 3 years ago, the longer-lasting effects of SARS-CoV-2 infection have continued to reveal themselves. Approximately 28% of Americans report having ever experienced post-COVID conditions, such as brain fog, postexertional malaise, and joint pain, and 11% say they are still experiencing these long-term effects. Now, new research is showing that people who have had COVID are more likely to newly develop an autoimmune disease. Exactly why this is happening is less clear, experts say.
Two preprint studies and one study published in a peer-reviewed journal provide strong evidence that patients who have been infected with SARS-CoV-2 are at elevated risk of developing an autoimmune disease. The studies retrospectively reviewed medical records from three countries and compared the incidence of new-onset autoimmune disease among patients who had polymerase chain reaction–confirmed COVID-19 and those who had never been diagnosed with the virus.
A study analyzing the health records of 3.8 million U.S. patients – more than 888,460 with confirmed COVID-19 – found that the COVID-19 group was two to three times as likely to develop various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. A U.K. preprint study that included more than 458,000 people with confirmed COVID found that those who had previously been infected with SARS-CoV-2 were 22% more likely to develop an autoimmune disease compared with the control group. In this cohort, the diseases most strongly associated with COVID-19 were type 1 diabetes, inflammatory bowel disease, and psoriasis. A preprint study from German researchers found that COVID-19 patients were almost 43% more likely to develop an autoimmune disease, compared with those who had never been infected. COVID-19 was most strongly linked to vasculitis.
These large studies are telling us, “Yes, this link is there, so we have to accept it,” Sonia Sharma, PhD, of the Center for Autoimmunity and Inflammation at the La Jolla (Calif.) Institute for Immunology, told this news organization. But this is not the first time that autoimmune diseases have been linked to previous infections.
Researchers have known for decades that Epstein-Barr virus infection is linked to several autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. More recent research suggests the virus may activate certain genes associated with these immune disorders. Hepatitis C virus can induce cryoglobulinemia, and infection with cytomegalovirus has been implicated in several autoimmune diseases. Bacterial infections have also been linked to autoimmunity, such as group A streptococcus and rheumatic fever, as well as salmonella and reactive arthritis, to name only a few.
“In a way, this isn’t necessarily a new concept to physicians, particularly rheumatologists,” said Jeffrey A. Sparks, MD, a rheumatologist at Brigham and Women’s Hospital in Boston. “There’s a fine line between appropriately clearing an infection and the body overreacting and setting off a cascade where the immune system is chronically overactive that can manifest as an autoimmune disease,” he told this news organization.
A dysregulated response to infection
It takes the immune system a week or two to develop antigen-specific antibodies to a new pathogen. But for patients with serious infections – in this instance, COVID-19 – that’s time they don’t have. Therefore, the immune system has an alternative pathway, called extrafollicular activation, that creates fast-acting antibodies, explained Matthew Woodruff, PhD, an instructor of immunology and rheumatology at Emory University, Atlanta.
The trade-off is that these antibodies are not as specific and can target the body’s own tissues. This dysregulation of antibody selection is generally short lived and fades when more targeted antibodies are produced and take over, but in some cases, this process can lead to high levels of self-targeting antibodies that can harm the body’s organs and tissues. Research also suggests that for patients who experience long COVID, the same autoantibodies that drive the initial immune response are detectable in the body months after infection, though it is not known whether these lingering immune cells cause these longer-lasting symptoms.
“If you have a virus that causes hyperinflammation plus organ damage, that is a recipe for disaster,” Dr. Sharma said. “It’s a recipe for autoantibodies and autoreactive T cells that down the road can attack the body’s own tissues, especially in people whose immune system is trained in such a way to cause self-reactivity,” she added.
This hyperinflammation can result in rare but serious complications, such as multisystem inflammatory syndrome in children and adults, which can occur 2-6 weeks after SARS-CoV-2 infection. But even in these patients with severe illness, organ-specific complications tend to resolve in 6 months with “no significant sequelae 1 year after diagnosis,” according to the Centers for Disease Control and Prevention. And while long COVID can last for a year or longer, data suggest that symptoms do eventually resolve for most people. What is not clear is why acute autoimmunity triggered by COVID-19 can become a chronic condition in certain patients.
Predisposition to autoimmunity
P. J. Utz, MD, PhD, professor of immunology and rheumatology at Stanford (Calif.) University, said that people who develop autoimmune disease after SARS-CoV-2 infection may have already been predisposed toward autoimmunity. Especially for autoimmune diseases such as type 1 diabetes and lupus, autoantibodies can appear and circulate in the body for more than a decade in some people before they present with any clinical symptoms. “Their immune system is primed such that if they get infected with something – or they have some other environmental trigger that maybe we don’t know about yet – that is enough to then push them over the edge so that they get full-blown autoimmunity,” he said. What is not known is whether these patients’ conditions would have advanced to true clinical disease had they not been infected, he said.
He also noted that the presence of autoantibodies does not necessarily mean someone has autoimmune disease; healthy people can also have autoantibodies, and everyone develops them with age. “My advice would be, ‘Don’t lose sleep over this,’ “ he said.
Dr. Sparks agreed that while these retrospective studies did show an elevated risk of autoimmune disease after COVID-19, that risk appears to be relatively small. “As a practicing rheumatologist, we aren’t seeing a stampede of patients with new-onset rheumatic diseases,” he said. “It’s not like we’re overwhelmed with autoimmune patients, even though almost everyone’s had COVID. So, if there is a risk, it’s very modest.”
Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Utz receives research funding from Pfizer. Dr. Sharma and Dr. Woodruff have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Looking at diseases associated with RA, May 2023
Although rheumatoid arthritis (RA) is well understood to be associated with cigarette smoking as well as with a risk for interstitial lung disease (ILD), its association with airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and with allergic disorders such as atopic dermatitis and allergic rhinitis, is unknown. Kim and colleagues performed a cross-sectional study using information from the Korean National Health and Nutrition Examination Survey by 334 respondents with RA and over 13,000 respondents without RA and analyzed the association of RA with asthma and asthma-related comorbidities. The prevalence of asthma was higher in respondents with RA (7.5% vs 2.8%; P < .001), but the prevalence of other allergic disorders and COPD wassimilar between groups. This finding in a small group of respondents is not striking and its importance is unclear compared with other nonallergic pulmonary disorders. Inferring a mechanistic connection to T-helper (Th) 1- vs Th2 immunity would thus be premature.
Baker and colleagues examined the risk for RA-associated ILD in patients taking different therapies for RA, a topic of great interest due to the frequency of this complication as well as uncertainty regarding its association with medications, including anti-tumor necrosis factor (TNF) agents and methotrexate. Using a claims database, they performed a retrospective study of patients with RA without existing ILD who were treated with a biologic (b) or targeted synthetic disease-modifying antirheumatic drugs (DMARD; abatacept, adalimumab, rituximab, tocilizumab, and tofacitinib). In over 28,000 patients with RA, incidence ratios for ILD were > 1 for all bDMARD, while the incidence ratio for ILD with tofacitinib was 1.47. As the group of patients treated with tofacitinib was the smallest, the reliability of this result is uncertain and thus not strong enough to suggest a protective effect or preference for this medication in patients with known ILD. However, prospective studies looking at ILD in RA patients taking tofacitinib would be of interest.
Kristensen and colleagues also looked at risks associated with tofacitinib and anti-TNF agents, in particular cardiovascular disease, malignancy, and venous thromboembolism, using data from the open-label randomized ORAL Surveillance study, which looked at patients taking 5 mg or 10 mg tofacitinib twice daily, adalimumab, or etanercept. The 10 mg dose was reduced to 5 mg twice daily after it was found that rates of pulmonary embolism were higher in the group taking the higher dose. Age and smoking are also known to be risk factors for malignancy and cardiovascular disease in patients with RA, and these findings carried through in this analysis as well. Within the study, patients taking tofacitinib over age 65 who had ever smoked had a higher risk for cardiovascular events, myocardial infarction, malignancy, venous thromboembolism, and death compared with patients on anti-TNF therapy, while patients taking tofacitinib who were younger than 65 and had never smoked had a risk similar to those on anti-TNF therapy.The study confirms prior knowledge regarding the risks of tofacitinib in different patient populations, suggesting that caution should be used with this medication in older patients and those who smoke.
Although rheumatoid arthritis (RA) is well understood to be associated with cigarette smoking as well as with a risk for interstitial lung disease (ILD), its association with airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and with allergic disorders such as atopic dermatitis and allergic rhinitis, is unknown. Kim and colleagues performed a cross-sectional study using information from the Korean National Health and Nutrition Examination Survey by 334 respondents with RA and over 13,000 respondents without RA and analyzed the association of RA with asthma and asthma-related comorbidities. The prevalence of asthma was higher in respondents with RA (7.5% vs 2.8%; P < .001), but the prevalence of other allergic disorders and COPD wassimilar between groups. This finding in a small group of respondents is not striking and its importance is unclear compared with other nonallergic pulmonary disorders. Inferring a mechanistic connection to T-helper (Th) 1- vs Th2 immunity would thus be premature.
Baker and colleagues examined the risk for RA-associated ILD in patients taking different therapies for RA, a topic of great interest due to the frequency of this complication as well as uncertainty regarding its association with medications, including anti-tumor necrosis factor (TNF) agents and methotrexate. Using a claims database, they performed a retrospective study of patients with RA without existing ILD who were treated with a biologic (b) or targeted synthetic disease-modifying antirheumatic drugs (DMARD; abatacept, adalimumab, rituximab, tocilizumab, and tofacitinib). In over 28,000 patients with RA, incidence ratios for ILD were > 1 for all bDMARD, while the incidence ratio for ILD with tofacitinib was 1.47. As the group of patients treated with tofacitinib was the smallest, the reliability of this result is uncertain and thus not strong enough to suggest a protective effect or preference for this medication in patients with known ILD. However, prospective studies looking at ILD in RA patients taking tofacitinib would be of interest.
Kristensen and colleagues also looked at risks associated with tofacitinib and anti-TNF agents, in particular cardiovascular disease, malignancy, and venous thromboembolism, using data from the open-label randomized ORAL Surveillance study, which looked at patients taking 5 mg or 10 mg tofacitinib twice daily, adalimumab, or etanercept. The 10 mg dose was reduced to 5 mg twice daily after it was found that rates of pulmonary embolism were higher in the group taking the higher dose. Age and smoking are also known to be risk factors for malignancy and cardiovascular disease in patients with RA, and these findings carried through in this analysis as well. Within the study, patients taking tofacitinib over age 65 who had ever smoked had a higher risk for cardiovascular events, myocardial infarction, malignancy, venous thromboembolism, and death compared with patients on anti-TNF therapy, while patients taking tofacitinib who were younger than 65 and had never smoked had a risk similar to those on anti-TNF therapy.The study confirms prior knowledge regarding the risks of tofacitinib in different patient populations, suggesting that caution should be used with this medication in older patients and those who smoke.
Although rheumatoid arthritis (RA) is well understood to be associated with cigarette smoking as well as with a risk for interstitial lung disease (ILD), its association with airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and with allergic disorders such as atopic dermatitis and allergic rhinitis, is unknown. Kim and colleagues performed a cross-sectional study using information from the Korean National Health and Nutrition Examination Survey by 334 respondents with RA and over 13,000 respondents without RA and analyzed the association of RA with asthma and asthma-related comorbidities. The prevalence of asthma was higher in respondents with RA (7.5% vs 2.8%; P < .001), but the prevalence of other allergic disorders and COPD wassimilar between groups. This finding in a small group of respondents is not striking and its importance is unclear compared with other nonallergic pulmonary disorders. Inferring a mechanistic connection to T-helper (Th) 1- vs Th2 immunity would thus be premature.
Baker and colleagues examined the risk for RA-associated ILD in patients taking different therapies for RA, a topic of great interest due to the frequency of this complication as well as uncertainty regarding its association with medications, including anti-tumor necrosis factor (TNF) agents and methotrexate. Using a claims database, they performed a retrospective study of patients with RA without existing ILD who were treated with a biologic (b) or targeted synthetic disease-modifying antirheumatic drugs (DMARD; abatacept, adalimumab, rituximab, tocilizumab, and tofacitinib). In over 28,000 patients with RA, incidence ratios for ILD were > 1 for all bDMARD, while the incidence ratio for ILD with tofacitinib was 1.47. As the group of patients treated with tofacitinib was the smallest, the reliability of this result is uncertain and thus not strong enough to suggest a protective effect or preference for this medication in patients with known ILD. However, prospective studies looking at ILD in RA patients taking tofacitinib would be of interest.
Kristensen and colleagues also looked at risks associated with tofacitinib and anti-TNF agents, in particular cardiovascular disease, malignancy, and venous thromboembolism, using data from the open-label randomized ORAL Surveillance study, which looked at patients taking 5 mg or 10 mg tofacitinib twice daily, adalimumab, or etanercept. The 10 mg dose was reduced to 5 mg twice daily after it was found that rates of pulmonary embolism were higher in the group taking the higher dose. Age and smoking are also known to be risk factors for malignancy and cardiovascular disease in patients with RA, and these findings carried through in this analysis as well. Within the study, patients taking tofacitinib over age 65 who had ever smoked had a higher risk for cardiovascular events, myocardial infarction, malignancy, venous thromboembolism, and death compared with patients on anti-TNF therapy, while patients taking tofacitinib who were younger than 65 and had never smoked had a risk similar to those on anti-TNF therapy.The study confirms prior knowledge regarding the risks of tofacitinib in different patient populations, suggesting that caution should be used with this medication in older patients and those who smoke.
RA causally associated with ischemic heart disease and myocardial infarction
Key clinical point: Rheumatoid arthritis (RA) is associated with a significant increase in the risk for ischemic heart disease (IHD) and myocardial infarction (MI), and managing RA activity may reduce the risk for cardiovascular diseases.
Major finding: RA is significantly associated with an increased risk for IHD (odds ratio [OR] 1.0006; P = .001551915) and MI (OR 1.0458; P = .001636), but not arrhythmia and atrial fibrillation.
Study details: Findings are from a two-sample Mendelian randomization study including patients and matched control individuals for RA (n = 14,361 and n = 43,923, respectively), MI (n = 12,801 and n = 187,840, respectively), IHD (n = 5861 and n = 457,149, respectively), atrial fibrillation (n = 60,620 and n = 970,216, respectively), and arrhythmia (n = 2545 and n = 460,388, respectively).
Disclosures: This study was supported by the Young Talent Development Plan of Changzhou Health Commission, China, and other sources. The authors declared no conflicts of interest.
Source: Wang M et al. Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: A Mendelian randomization study. Front Cardiovasc Med. 2023;10:1099861 (Mar 17). Doi: 10.3389/fcvm.2023.1099861
Key clinical point: Rheumatoid arthritis (RA) is associated with a significant increase in the risk for ischemic heart disease (IHD) and myocardial infarction (MI), and managing RA activity may reduce the risk for cardiovascular diseases.
Major finding: RA is significantly associated with an increased risk for IHD (odds ratio [OR] 1.0006; P = .001551915) and MI (OR 1.0458; P = .001636), but not arrhythmia and atrial fibrillation.
Study details: Findings are from a two-sample Mendelian randomization study including patients and matched control individuals for RA (n = 14,361 and n = 43,923, respectively), MI (n = 12,801 and n = 187,840, respectively), IHD (n = 5861 and n = 457,149, respectively), atrial fibrillation (n = 60,620 and n = 970,216, respectively), and arrhythmia (n = 2545 and n = 460,388, respectively).
Disclosures: This study was supported by the Young Talent Development Plan of Changzhou Health Commission, China, and other sources. The authors declared no conflicts of interest.
Source: Wang M et al. Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: A Mendelian randomization study. Front Cardiovasc Med. 2023;10:1099861 (Mar 17). Doi: 10.3389/fcvm.2023.1099861
Key clinical point: Rheumatoid arthritis (RA) is associated with a significant increase in the risk for ischemic heart disease (IHD) and myocardial infarction (MI), and managing RA activity may reduce the risk for cardiovascular diseases.
Major finding: RA is significantly associated with an increased risk for IHD (odds ratio [OR] 1.0006; P = .001551915) and MI (OR 1.0458; P = .001636), but not arrhythmia and atrial fibrillation.
Study details: Findings are from a two-sample Mendelian randomization study including patients and matched control individuals for RA (n = 14,361 and n = 43,923, respectively), MI (n = 12,801 and n = 187,840, respectively), IHD (n = 5861 and n = 457,149, respectively), atrial fibrillation (n = 60,620 and n = 970,216, respectively), and arrhythmia (n = 2545 and n = 460,388, respectively).
Disclosures: This study was supported by the Young Talent Development Plan of Changzhou Health Commission, China, and other sources. The authors declared no conflicts of interest.
Source: Wang M et al. Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: A Mendelian randomization study. Front Cardiovasc Med. 2023;10:1099861 (Mar 17). Doi: 10.3389/fcvm.2023.1099861
Mortality risk accrues with time after diagnosis of RA
Key clinical point: Mortality risk varied with time and increased only during the second not the first decade after the diagnosis of rheumatoid arthritis (RA), with respiratory diseases potentially surpassing cardiovascular diseases as major attributable factors.
Major finding: Increase in mortality was observed at 20 years (standardized mortality ratio [SMR] 1.49; P < .001) but not during the first 10 years (P = .44) after RA diagnosis, with pneumonia (cause-specific SMR 5.22; 95% CI 2.26-10.29) and interstitial lung disease (cause-specific SMR 7.64; 95% CI 2.98-14.69) being major contributors.
Study details: Findings are from an analysis of 1895 patients with RA from the Australian Rheumatology Association Database (ARAD) registry who received biologic, targeted synthetic, or conventional synthetic disease-modifying antirheumatic drugs.
Disclosures: ARAD received support through the Australian Rheumatology Association from various sources. Three authors declared receiving grants, funding, or honoraria from different sources unrelated to this study.
Source: Black RJ et al. Mortality estimates and excess mortality in rheumatoid arthritis. Rheumatology (Oxford). 2023 (Mar 15). Doi: 10.1093/rheumatology/kead106
Key clinical point: Mortality risk varied with time and increased only during the second not the first decade after the diagnosis of rheumatoid arthritis (RA), with respiratory diseases potentially surpassing cardiovascular diseases as major attributable factors.
Major finding: Increase in mortality was observed at 20 years (standardized mortality ratio [SMR] 1.49; P < .001) but not during the first 10 years (P = .44) after RA diagnosis, with pneumonia (cause-specific SMR 5.22; 95% CI 2.26-10.29) and interstitial lung disease (cause-specific SMR 7.64; 95% CI 2.98-14.69) being major contributors.
Study details: Findings are from an analysis of 1895 patients with RA from the Australian Rheumatology Association Database (ARAD) registry who received biologic, targeted synthetic, or conventional synthetic disease-modifying antirheumatic drugs.
Disclosures: ARAD received support through the Australian Rheumatology Association from various sources. Three authors declared receiving grants, funding, or honoraria from different sources unrelated to this study.
Source: Black RJ et al. Mortality estimates and excess mortality in rheumatoid arthritis. Rheumatology (Oxford). 2023 (Mar 15). Doi: 10.1093/rheumatology/kead106
Key clinical point: Mortality risk varied with time and increased only during the second not the first decade after the diagnosis of rheumatoid arthritis (RA), with respiratory diseases potentially surpassing cardiovascular diseases as major attributable factors.
Major finding: Increase in mortality was observed at 20 years (standardized mortality ratio [SMR] 1.49; P < .001) but not during the first 10 years (P = .44) after RA diagnosis, with pneumonia (cause-specific SMR 5.22; 95% CI 2.26-10.29) and interstitial lung disease (cause-specific SMR 7.64; 95% CI 2.98-14.69) being major contributors.
Study details: Findings are from an analysis of 1895 patients with RA from the Australian Rheumatology Association Database (ARAD) registry who received biologic, targeted synthetic, or conventional synthetic disease-modifying antirheumatic drugs.
Disclosures: ARAD received support through the Australian Rheumatology Association from various sources. Three authors declared receiving grants, funding, or honoraria from different sources unrelated to this study.
Source: Black RJ et al. Mortality estimates and excess mortality in rheumatoid arthritis. Rheumatology (Oxford). 2023 (Mar 15). Doi: 10.1093/rheumatology/kead106
RA raises risk for bronchial asthma and asthma-related comorbidities
Key clinical point: Rheumatoid arthritis (RA) was significantly associated with an increased risk for bronchial asthma, allergic rhinitis, and sinusitis, and a notable interrelation was observed between the presence of asthma and obesity in patients with RA.
Major finding: Presence of RA significantly increased the risk for asthma (odds ratio [OR] 2.32; 95% CI 1.51-3.57), allergic rhinitis (OR 1.51; 95% CI 1.08-2.10), and sinusitis (OR 1.64; 95% CI 1.08-2.50) in the whole cohort and the prevalence of obesity in patients with asthma (64.0% vs 40.2%; P = .034).
Study details: This population-based cross-sectional study included 14,272 participants, of which 334 had RA.
Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korean Government. The authors declared no conflicts of interest.
Source: Kim JG et al. Association of rheumatoid arthritis with bronchial asthma and asthma-related comorbidities: A population-based national surveillance study. Front Med (Lausanne). 2023;10:1006290 (Mar 10). Doi: 10.3389/fmed.2023.1006290
Key clinical point: Rheumatoid arthritis (RA) was significantly associated with an increased risk for bronchial asthma, allergic rhinitis, and sinusitis, and a notable interrelation was observed between the presence of asthma and obesity in patients with RA.
Major finding: Presence of RA significantly increased the risk for asthma (odds ratio [OR] 2.32; 95% CI 1.51-3.57), allergic rhinitis (OR 1.51; 95% CI 1.08-2.10), and sinusitis (OR 1.64; 95% CI 1.08-2.50) in the whole cohort and the prevalence of obesity in patients with asthma (64.0% vs 40.2%; P = .034).
Study details: This population-based cross-sectional study included 14,272 participants, of which 334 had RA.
Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korean Government. The authors declared no conflicts of interest.
Source: Kim JG et al. Association of rheumatoid arthritis with bronchial asthma and asthma-related comorbidities: A population-based national surveillance study. Front Med (Lausanne). 2023;10:1006290 (Mar 10). Doi: 10.3389/fmed.2023.1006290
Key clinical point: Rheumatoid arthritis (RA) was significantly associated with an increased risk for bronchial asthma, allergic rhinitis, and sinusitis, and a notable interrelation was observed between the presence of asthma and obesity in patients with RA.
Major finding: Presence of RA significantly increased the risk for asthma (odds ratio [OR] 2.32; 95% CI 1.51-3.57), allergic rhinitis (OR 1.51; 95% CI 1.08-2.10), and sinusitis (OR 1.64; 95% CI 1.08-2.50) in the whole cohort and the prevalence of obesity in patients with asthma (64.0% vs 40.2%; P = .034).
Study details: This population-based cross-sectional study included 14,272 participants, of which 334 had RA.
Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korean Government. The authors declared no conflicts of interest.
Source: Kim JG et al. Association of rheumatoid arthritis with bronchial asthma and asthma-related comorbidities: A population-based national surveillance study. Front Med (Lausanne). 2023;10:1006290 (Mar 10). Doi: 10.3389/fmed.2023.1006290
Meta-analysis reveals superior efficacy and safety outcomes with abatacept in RA
Key clinical point: Abatacept with or without conventional synthetic disease-modifying antirheumatic drugs (csDMARD) demonstrated better efficacy and favorable safety outcomes compared with placebo, csDMARD, or other biologic DMARD (bDMARD) in patients with rheumatoid arthritis (RA).
Major finding: Patients treated with abatacept with or without csDMARD vs placebo, csDMARD, or other bDMARD were more likely to achieve American College of Rheumatology (ACR) 20 (relative risk [RR] 1.57; 95% CI 1.27-1.93), ACR50 (RR 1.84; 95% CI 1.38-2.44), and ACR70 (RR 2.36; 95% CI 1.60-3.47) responses, as well as were less likely to experience adverse events (RR 0.93; 95% CI 0.84-1.03).
Study details: Findings are from a systematic review and meta-analysis of 13 randomized controlled trials including 5978 patients with RA who were randomly assigned to receive abatacept alone, abatacept with csDMARD, placebo, csDMARD, or other bDMARD.
Disclosures: This study was supported by the National Key R&D Program of China. The authors did not report conflicts of interest.
Source: Ahamada MM and Wu X. Analysis of efficacy and safety of abatacept for rheumatoid arthritis: Systematic review and meta-analysis. Clin Exp Rheumatol. 2023 (Mar 7). Doi: 10.55563/clinexprheumatol/2xjg0d
Key clinical point: Abatacept with or without conventional synthetic disease-modifying antirheumatic drugs (csDMARD) demonstrated better efficacy and favorable safety outcomes compared with placebo, csDMARD, or other biologic DMARD (bDMARD) in patients with rheumatoid arthritis (RA).
Major finding: Patients treated with abatacept with or without csDMARD vs placebo, csDMARD, or other bDMARD were more likely to achieve American College of Rheumatology (ACR) 20 (relative risk [RR] 1.57; 95% CI 1.27-1.93), ACR50 (RR 1.84; 95% CI 1.38-2.44), and ACR70 (RR 2.36; 95% CI 1.60-3.47) responses, as well as were less likely to experience adverse events (RR 0.93; 95% CI 0.84-1.03).
Study details: Findings are from a systematic review and meta-analysis of 13 randomized controlled trials including 5978 patients with RA who were randomly assigned to receive abatacept alone, abatacept with csDMARD, placebo, csDMARD, or other bDMARD.
Disclosures: This study was supported by the National Key R&D Program of China. The authors did not report conflicts of interest.
Source: Ahamada MM and Wu X. Analysis of efficacy and safety of abatacept for rheumatoid arthritis: Systematic review and meta-analysis. Clin Exp Rheumatol. 2023 (Mar 7). Doi: 10.55563/clinexprheumatol/2xjg0d
Key clinical point: Abatacept with or without conventional synthetic disease-modifying antirheumatic drugs (csDMARD) demonstrated better efficacy and favorable safety outcomes compared with placebo, csDMARD, or other biologic DMARD (bDMARD) in patients with rheumatoid arthritis (RA).
Major finding: Patients treated with abatacept with or without csDMARD vs placebo, csDMARD, or other bDMARD were more likely to achieve American College of Rheumatology (ACR) 20 (relative risk [RR] 1.57; 95% CI 1.27-1.93), ACR50 (RR 1.84; 95% CI 1.38-2.44), and ACR70 (RR 2.36; 95% CI 1.60-3.47) responses, as well as were less likely to experience adverse events (RR 0.93; 95% CI 0.84-1.03).
Study details: Findings are from a systematic review and meta-analysis of 13 randomized controlled trials including 5978 patients with RA who were randomly assigned to receive abatacept alone, abatacept with csDMARD, placebo, csDMARD, or other bDMARD.
Disclosures: This study was supported by the National Key R&D Program of China. The authors did not report conflicts of interest.
Source: Ahamada MM and Wu X. Analysis of efficacy and safety of abatacept for rheumatoid arthritis: Systematic review and meta-analysis. Clin Exp Rheumatol. 2023 (Mar 7). Doi: 10.55563/clinexprheumatol/2xjg0d
Factors to guide individualized benefit-risk assessment and decision-making with tofacitinib in RA
Key clinical point: Factors like age ≥65 years or current or former smoking accounted for excess risk with tofacitinib vs tumor necrosis factor inhibitor (TNFi) use in patients with rheumatoid arthritis (RA).
Major finding: Tofacitinib vs TNFi significantly increased the risk for malignancies (hazard ratio [HR] 1.55; 95% CI 1.05-2.30), venous thromboembolism (HR 5.19; 95% CI 1.86-14.46), and all-cause death (HR 2.24; 95% CI 1.20-4.19) among patients who were ≥65 years old or ever smokers, but not among those aged <65 years and never smokers.
Study details: Findings are from a post hoc analysis of the ORAL Surveillance trial including patients with RA (n = 4362) treated with tofacitinib or TNFi and an exploratory analysis of RA, PsA, and ulcerative colitis (UC) development programs including tofacitinib-exposed patients with RA (n = 7964), psoriatic arthritis (n = 783), and UC (n = 1157).
Disclosures: This study was sponsored by Pfizer Inc. Six authors declared being employees and stockholders of Pfizer. Two authors declared receiving speaking, consulting, or lecture fees or research grants from Pfizer and other sources.
Source: Kristensen LE et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: An analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 (Mar 17). Doi: 10.1136/ard-2022-223715
Key clinical point: Factors like age ≥65 years or current or former smoking accounted for excess risk with tofacitinib vs tumor necrosis factor inhibitor (TNFi) use in patients with rheumatoid arthritis (RA).
Major finding: Tofacitinib vs TNFi significantly increased the risk for malignancies (hazard ratio [HR] 1.55; 95% CI 1.05-2.30), venous thromboembolism (HR 5.19; 95% CI 1.86-14.46), and all-cause death (HR 2.24; 95% CI 1.20-4.19) among patients who were ≥65 years old or ever smokers, but not among those aged <65 years and never smokers.
Study details: Findings are from a post hoc analysis of the ORAL Surveillance trial including patients with RA (n = 4362) treated with tofacitinib or TNFi and an exploratory analysis of RA, PsA, and ulcerative colitis (UC) development programs including tofacitinib-exposed patients with RA (n = 7964), psoriatic arthritis (n = 783), and UC (n = 1157).
Disclosures: This study was sponsored by Pfizer Inc. Six authors declared being employees and stockholders of Pfizer. Two authors declared receiving speaking, consulting, or lecture fees or research grants from Pfizer and other sources.
Source: Kristensen LE et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: An analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 (Mar 17). Doi: 10.1136/ard-2022-223715
Key clinical point: Factors like age ≥65 years or current or former smoking accounted for excess risk with tofacitinib vs tumor necrosis factor inhibitor (TNFi) use in patients with rheumatoid arthritis (RA).
Major finding: Tofacitinib vs TNFi significantly increased the risk for malignancies (hazard ratio [HR] 1.55; 95% CI 1.05-2.30), venous thromboembolism (HR 5.19; 95% CI 1.86-14.46), and all-cause death (HR 2.24; 95% CI 1.20-4.19) among patients who were ≥65 years old or ever smokers, but not among those aged <65 years and never smokers.
Study details: Findings are from a post hoc analysis of the ORAL Surveillance trial including patients with RA (n = 4362) treated with tofacitinib or TNFi and an exploratory analysis of RA, PsA, and ulcerative colitis (UC) development programs including tofacitinib-exposed patients with RA (n = 7964), psoriatic arthritis (n = 783), and UC (n = 1157).
Disclosures: This study was sponsored by Pfizer Inc. Six authors declared being employees and stockholders of Pfizer. Two authors declared receiving speaking, consulting, or lecture fees or research grants from Pfizer and other sources.
Source: Kristensen LE et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: An analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 (Mar 17). Doi: 10.1136/ard-2022-223715