Rheumatology News

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

A version of this article first appeared on Medscape.com.

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

A version of this article first appeared on Medscape.com.

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

A version of this article first appeared on Medscape.com.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Researchers have yet to crack how to analyze synovial tissue biopsy specimens to predict treatment responses for patients with rheumatoid arthritis.

According to new research, classifying patients by synovial fluid B-cell status was not reliable in predicting treatment response to etanercept, tocilizumab, or rituximab. More comprehensive molecular analyses may hold promise in developing models to predict treatment of a disease as heterogeneous as RA, wrote the authors, led by chief investigator Costantino Pitzalis, MD, head of the Centre for Experimental Medicine and Rheumatology at Queen Mary University of London.

The article was published in the November 2023 issue of The Lancet Rheumatology..
 

Trial-and-error treatment

Because clinicians do not have a way to reliably predict how patients may respond to certain medications, the current RA treatments involve trial and error.

Courtesy Dr. Arthur Mandelin, Northwestern University

“Both with regard to the first conventional synthetic disease-modifying antirheumatic drug (DMARD) for all patients and the first biologic DMARD for the subgroup of patients requiring these drugs, the choice of a drug is based on pragmatic arguments rather than on individual patient characteristics,” Annette H. van der Helm-van Mil, MD, PhD, professor of rheumatology at the Leiden University Medical Center, the Netherlands, wrote in an accompanying editorial.

Most research on predicting treatment response has used clinical features and blood biomarkers, but neither approach is reliably predictive. “Precision medicine, therefore, remains elusive,” she said. Newer research has focused on synovial tissue biopsy to inform research decisions.
 

The STRAP studies

In this newest study, researchers combined data from two clinical studies with identical design: the Stratification of Biological Therapies by Pathobiology in Biologic-Naive Patients With Rheumatoid Arthritis (STRAP) trial, taking place in the United Kingdom, and STRAP-EU, which recruited patients from the European Union. The trials are the largest biopsy-driven trials to date, according to the researchers.

In total, researchers recruited 223 biologic-naive adult patients from 26 universities in the United Kingdom and Europe. Participants underwent ultrasound-guided synovial tissue biopsy and were then randomly assigned to receive etanercept (72 patients), tocilizumab (73 patients), or rituximab (78 patients). In a histologic analysis, 121 patients were characterized as B-cell poor (BCP), 100 patients were classified as B-cell rich (BCR), and two patients were classified as undetermined.

“We hypothesized that patients with a low synovial histological or molecular B-cell score would have a lower response to rituximab than to etanercept or tocilizumab,” the authors wrote.

However, among the BCP patients, there were no significant differences between responses to treatment at week 16 in the rituximab group compared with the etanercept and tocilizumab groups put together. In both groups, around 60% of patients achieved the primary endpoint of at least 20% improvement in American College of Rheumatology response criteria.

The results suggest that “a dichotomic classification into synovial B cell poor versus rich is unable to predict treatment response in patients treated with rituximab compared with etanercept or tocilizumab,” the authors wrote.

The findings echo work from the same group of researchers in 2021. This study – the R4RA trial – enrolled 164 patients who previously had an inadequate response to tumor necrosis factor blockers. Researchers then used a similar histologic approach to compare patients’ responses to tocilizumab or rituximab.

Among patients classified as BCP, there was not a significant difference in treatment response between the tocilizumab group and the rituximab group. However, classifying patients as BCP with RNA sequencing did make a difference. In this subgroup, patients given tocilizumab demonstrated a significantly higher response rate than those treated with rituximab.
 

Molecular-level analyses needed

This 2021 study showed – and this most recent study further confirmed – that “histology is not the way to understand what’s going on with or be predictive with tissue,” said Harris R. Perlman, PhD, chief of rheumatology at Northwestern University in Chicago. He was not involved with the research.

Dr. Perlman

“Most people now believe that you really have to understand the tissue on a single-cell basis – using the gene expression of each individual cell – to really give you an idea of what’s happening in tissue,” he noted.

“RA continues to tell us that it is more complex than just something dichotomous,” added Elena Myasoedova, MD, PhD, director of the Inflammatory Arthritis Subspecialty Group at the Mayo Clinic in Rochester, Minn. She was not involved with the work.

Dr. Myasoedova

“Understanding more about the heterogeneity using different ‘-omics’ approaches and introducing a two- or three-dimensional approach with spatial biology can be helpful,” she said.

Spatial transcriptomics, for example, allows scientists to measure all gene activity in a tissue sample and to map where that gene activity is occurring.

“It helps us to understand and visualize molecules and their unique context within individual cells and tissues,” Dr. Myasoedova explained.

With advanced molecular analyses already available, Dr. Perlman is adamant that synovial tissue remains the key to unlocking precision medicine.

“The tissue is the golden ticket,” he said, “but it’s how you analyze it.”

And it’s clear that older analytic methods – such as histology – are not enough, he said.

A larger study of a size similar to that of STRAP that incorporates multiple sources of patient information, from gene expression to clinical symptoms, to create a predictive model would be key to understanding how to move the field of precision treatment for RA forward, he added.

“Precision medicine for RA is close,” he said. “We still have to get the numbers.”

The STRAP and STRAP-EU trials were jointly funded by the UK Medical Research Council and Versus Arthritis. Pfizer and Roche donated the study drugs through an investigator-sponsored research grant. Many authors, including Dr. Pitzalis, have multiple financial relationships with pharmaceutical companies. Dr. Van der Helm-van Mil and Dr. Myasoedova have disclosed no relevant financial relationships. Dr. Perlman consults for AbbVie, AnaptysBio, Exagen, Janssen, and Kiniksa.
 

A version of this article first appeared on Medscape.com.

Researchers have yet to crack how to analyze synovial tissue biopsy specimens to predict treatment responses for patients with rheumatoid arthritis.

According to new research, classifying patients by synovial fluid B-cell status was not reliable in predicting treatment response to etanercept, tocilizumab, or rituximab. More comprehensive molecular analyses may hold promise in developing models to predict treatment of a disease as heterogeneous as RA, wrote the authors, led by chief investigator Costantino Pitzalis, MD, head of the Centre for Experimental Medicine and Rheumatology at Queen Mary University of London.

The article was published in the November 2023 issue of The Lancet Rheumatology..
 

Trial-and-error treatment

Because clinicians do not have a way to reliably predict how patients may respond to certain medications, the current RA treatments involve trial and error.

Courtesy Dr. Arthur Mandelin, Northwestern University

“Both with regard to the first conventional synthetic disease-modifying antirheumatic drug (DMARD) for all patients and the first biologic DMARD for the subgroup of patients requiring these drugs, the choice of a drug is based on pragmatic arguments rather than on individual patient characteristics,” Annette H. van der Helm-van Mil, MD, PhD, professor of rheumatology at the Leiden University Medical Center, the Netherlands, wrote in an accompanying editorial.

Most research on predicting treatment response has used clinical features and blood biomarkers, but neither approach is reliably predictive. “Precision medicine, therefore, remains elusive,” she said. Newer research has focused on synovial tissue biopsy to inform research decisions.
 

The STRAP studies

In this newest study, researchers combined data from two clinical studies with identical design: the Stratification of Biological Therapies by Pathobiology in Biologic-Naive Patients With Rheumatoid Arthritis (STRAP) trial, taking place in the United Kingdom, and STRAP-EU, which recruited patients from the European Union. The trials are the largest biopsy-driven trials to date, according to the researchers.

In total, researchers recruited 223 biologic-naive adult patients from 26 universities in the United Kingdom and Europe. Participants underwent ultrasound-guided synovial tissue biopsy and were then randomly assigned to receive etanercept (72 patients), tocilizumab (73 patients), or rituximab (78 patients). In a histologic analysis, 121 patients were characterized as B-cell poor (BCP), 100 patients were classified as B-cell rich (BCR), and two patients were classified as undetermined.

“We hypothesized that patients with a low synovial histological or molecular B-cell score would have a lower response to rituximab than to etanercept or tocilizumab,” the authors wrote.

However, among the BCP patients, there were no significant differences between responses to treatment at week 16 in the rituximab group compared with the etanercept and tocilizumab groups put together. In both groups, around 60% of patients achieved the primary endpoint of at least 20% improvement in American College of Rheumatology response criteria.

The results suggest that “a dichotomic classification into synovial B cell poor versus rich is unable to predict treatment response in patients treated with rituximab compared with etanercept or tocilizumab,” the authors wrote.

The findings echo work from the same group of researchers in 2021. This study – the R4RA trial – enrolled 164 patients who previously had an inadequate response to tumor necrosis factor blockers. Researchers then used a similar histologic approach to compare patients’ responses to tocilizumab or rituximab.

Among patients classified as BCP, there was not a significant difference in treatment response between the tocilizumab group and the rituximab group. However, classifying patients as BCP with RNA sequencing did make a difference. In this subgroup, patients given tocilizumab demonstrated a significantly higher response rate than those treated with rituximab.
 

Molecular-level analyses needed

This 2021 study showed – and this most recent study further confirmed – that “histology is not the way to understand what’s going on with or be predictive with tissue,” said Harris R. Perlman, PhD, chief of rheumatology at Northwestern University in Chicago. He was not involved with the research.

Dr. Perlman

“Most people now believe that you really have to understand the tissue on a single-cell basis – using the gene expression of each individual cell – to really give you an idea of what’s happening in tissue,” he noted.

“RA continues to tell us that it is more complex than just something dichotomous,” added Elena Myasoedova, MD, PhD, director of the Inflammatory Arthritis Subspecialty Group at the Mayo Clinic in Rochester, Minn. She was not involved with the work.

Dr. Myasoedova

“Understanding more about the heterogeneity using different ‘-omics’ approaches and introducing a two- or three-dimensional approach with spatial biology can be helpful,” she said.

Spatial transcriptomics, for example, allows scientists to measure all gene activity in a tissue sample and to map where that gene activity is occurring.

“It helps us to understand and visualize molecules and their unique context within individual cells and tissues,” Dr. Myasoedova explained.

With advanced molecular analyses already available, Dr. Perlman is adamant that synovial tissue remains the key to unlocking precision medicine.

“The tissue is the golden ticket,” he said, “but it’s how you analyze it.”

And it’s clear that older analytic methods – such as histology – are not enough, he said.

A larger study of a size similar to that of STRAP that incorporates multiple sources of patient information, from gene expression to clinical symptoms, to create a predictive model would be key to understanding how to move the field of precision treatment for RA forward, he added.

“Precision medicine for RA is close,” he said. “We still have to get the numbers.”

The STRAP and STRAP-EU trials were jointly funded by the UK Medical Research Council and Versus Arthritis. Pfizer and Roche donated the study drugs through an investigator-sponsored research grant. Many authors, including Dr. Pitzalis, have multiple financial relationships with pharmaceutical companies. Dr. Van der Helm-van Mil and Dr. Myasoedova have disclosed no relevant financial relationships. Dr. Perlman consults for AbbVie, AnaptysBio, Exagen, Janssen, and Kiniksa.
 

A version of this article first appeared on Medscape.com.

Researchers have yet to crack how to analyze synovial tissue biopsy specimens to predict treatment responses for patients with rheumatoid arthritis.

According to new research, classifying patients by synovial fluid B-cell status was not reliable in predicting treatment response to etanercept, tocilizumab, or rituximab. More comprehensive molecular analyses may hold promise in developing models to predict treatment of a disease as heterogeneous as RA, wrote the authors, led by chief investigator Costantino Pitzalis, MD, head of the Centre for Experimental Medicine and Rheumatology at Queen Mary University of London.

The article was published in the November 2023 issue of The Lancet Rheumatology..
 

Trial-and-error treatment

Because clinicians do not have a way to reliably predict how patients may respond to certain medications, the current RA treatments involve trial and error.

Courtesy Dr. Arthur Mandelin, Northwestern University

“Both with regard to the first conventional synthetic disease-modifying antirheumatic drug (DMARD) for all patients and the first biologic DMARD for the subgroup of patients requiring these drugs, the choice of a drug is based on pragmatic arguments rather than on individual patient characteristics,” Annette H. van der Helm-van Mil, MD, PhD, professor of rheumatology at the Leiden University Medical Center, the Netherlands, wrote in an accompanying editorial.

Most research on predicting treatment response has used clinical features and blood biomarkers, but neither approach is reliably predictive. “Precision medicine, therefore, remains elusive,” she said. Newer research has focused on synovial tissue biopsy to inform research decisions.
 

The STRAP studies

In this newest study, researchers combined data from two clinical studies with identical design: the Stratification of Biological Therapies by Pathobiology in Biologic-Naive Patients With Rheumatoid Arthritis (STRAP) trial, taking place in the United Kingdom, and STRAP-EU, which recruited patients from the European Union. The trials are the largest biopsy-driven trials to date, according to the researchers.

In total, researchers recruited 223 biologic-naive adult patients from 26 universities in the United Kingdom and Europe. Participants underwent ultrasound-guided synovial tissue biopsy and were then randomly assigned to receive etanercept (72 patients), tocilizumab (73 patients), or rituximab (78 patients). In a histologic analysis, 121 patients were characterized as B-cell poor (BCP), 100 patients were classified as B-cell rich (BCR), and two patients were classified as undetermined.

“We hypothesized that patients with a low synovial histological or molecular B-cell score would have a lower response to rituximab than to etanercept or tocilizumab,” the authors wrote.

However, among the BCP patients, there were no significant differences between responses to treatment at week 16 in the rituximab group compared with the etanercept and tocilizumab groups put together. In both groups, around 60% of patients achieved the primary endpoint of at least 20% improvement in American College of Rheumatology response criteria.

The results suggest that “a dichotomic classification into synovial B cell poor versus rich is unable to predict treatment response in patients treated with rituximab compared with etanercept or tocilizumab,” the authors wrote.

The findings echo work from the same group of researchers in 2021. This study – the R4RA trial – enrolled 164 patients who previously had an inadequate response to tumor necrosis factor blockers. Researchers then used a similar histologic approach to compare patients’ responses to tocilizumab or rituximab.

Among patients classified as BCP, there was not a significant difference in treatment response between the tocilizumab group and the rituximab group. However, classifying patients as BCP with RNA sequencing did make a difference. In this subgroup, patients given tocilizumab demonstrated a significantly higher response rate than those treated with rituximab.
 

Molecular-level analyses needed

This 2021 study showed – and this most recent study further confirmed – that “histology is not the way to understand what’s going on with or be predictive with tissue,” said Harris R. Perlman, PhD, chief of rheumatology at Northwestern University in Chicago. He was not involved with the research.

Dr. Perlman

“Most people now believe that you really have to understand the tissue on a single-cell basis – using the gene expression of each individual cell – to really give you an idea of what’s happening in tissue,” he noted.

“RA continues to tell us that it is more complex than just something dichotomous,” added Elena Myasoedova, MD, PhD, director of the Inflammatory Arthritis Subspecialty Group at the Mayo Clinic in Rochester, Minn. She was not involved with the work.

Dr. Myasoedova

“Understanding more about the heterogeneity using different ‘-omics’ approaches and introducing a two- or three-dimensional approach with spatial biology can be helpful,” she said.

Spatial transcriptomics, for example, allows scientists to measure all gene activity in a tissue sample and to map where that gene activity is occurring.

“It helps us to understand and visualize molecules and their unique context within individual cells and tissues,” Dr. Myasoedova explained.

With advanced molecular analyses already available, Dr. Perlman is adamant that synovial tissue remains the key to unlocking precision medicine.

“The tissue is the golden ticket,” he said, “but it’s how you analyze it.”

And it’s clear that older analytic methods – such as histology – are not enough, he said.

A larger study of a size similar to that of STRAP that incorporates multiple sources of patient information, from gene expression to clinical symptoms, to create a predictive model would be key to understanding how to move the field of precision treatment for RA forward, he added.

“Precision medicine for RA is close,” he said. “We still have to get the numbers.”

The STRAP and STRAP-EU trials were jointly funded by the UK Medical Research Council and Versus Arthritis. Pfizer and Roche donated the study drugs through an investigator-sponsored research grant. Many authors, including Dr. Pitzalis, have multiple financial relationships with pharmaceutical companies. Dr. Van der Helm-van Mil and Dr. Myasoedova have disclosed no relevant financial relationships. Dr. Perlman consults for AbbVie, AnaptysBio, Exagen, Janssen, and Kiniksa.
 

A version of this article first appeared on Medscape.com.

Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.

Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.

Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.

Astrid Gast/Thinkstock

The study was published online October 12 in The Lancet.

METHODS makes improvements on past studies

While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.

Dr. Cicuttini

In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS. 
 

Study details and results

METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.

The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.

The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.

The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.

The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).

MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study. 
 

Qualifications and considerations for MTX use

Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.

Dr. Nelson

Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.

She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.

Nicolas Tourrenc

“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.

Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”

Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”

In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.” 

While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.

The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.

Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.

Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial). 

The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.

Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.

Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.

Astrid Gast/Thinkstock

The study was published online October 12 in The Lancet.

METHODS makes improvements on past studies

While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.

Dr. Cicuttini

In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS. 
 

Study details and results

METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.

The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.

The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.

The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.

The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).

MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study. 
 

Qualifications and considerations for MTX use

Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.

Dr. Nelson

Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.

She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.

Nicolas Tourrenc

“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.

Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”

Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”

In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.” 

While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.

The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.

Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.

Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial). 

The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Patients with hand osteoarthritis (OA) and MRI-detected synovitis who took methotrexate (MTX) 20 mg weekly over a 6-month period had a significant and potentially clinically meaningful reduction in pain and stiffness over those who received placebo in the first randomized controlled trial of its kind to show positive results with the drug.

Patients who were randomly assigned to MTX took 10 mg orally for the first 4 weeks then increased to 20 mg for the rest of the trial, with differences in the primary outcome of pain measured by visual analog scale (VAS) first becoming significant over placebo at 3 months.

Senior author of the METHODS study (Methotrexate to Treat Hand Osteoarthritis with Synovitis), Flavia Cicuttini, PhD, MSc, head of the musculoskeletal unit at Monash University and head of rheumatology at Alfred Hospital, Melbourne, Australia, noted that the effect of MTX was higher than effect sizes that have been reported for NSAIDs on pain in hip or knee OA.

Astrid Gast/Thinkstock

The study was published online October 12 in The Lancet.

METHODS makes improvements on past studies

While OA is traditionally categorized as a noninflammatory process, it’s known that there are some patients who have a clinical phenotype characterized by joint swelling (synovitis) and others develop erosive disease. MTX is one of the most common therapies for inflammatory arthritis and standard of care for rheumatoid arthritis (RA) management. Previous studies of methotrexate showed lack of efficacy in hand OA but may have been because of the use of a low dose, poor power due to moderate sample size, and failure to target the specific inflammatory OA phenotype.

Dr. Cicuttini

In an interview, Dr. Cicuttini noted the selection of methotrexate for this trial was intentional. “We considered the evidence and decided to test methotrexate because we know it is effective in inflammatory arthritis, and its mode of action is broader than the more selective anti-TNF [tumor necrosis factor] agents,” which she noted have failed in prior hand OA trials. She also noted that the only previous randomized controlled trial of MTX tested a dose of 10 mg/week, rather than the 20 mg/week dose used in METHODS. 
 

Study details and results

METHODS was a randomized, double-blind, placebo-controlled trial at multiple sites within Australia. Patients were recruited from 2017 to 2022, with a temporary pause in 2020 during the COVID-19 pandemic because of safety concerns regarding MTX use. Participants included in this study were aged 40-75 years, had pain in hand joints for most days in the past 3 months, and a pain score of at least 40 mm on a 100-mm VAS in the past 7 days.

The participants’ hand OA fulfilled American College of Rheumatology criteria, radiographic osteoarthritis (Kellgren and Lawrence grade 2 or more) in at least one joint, and MRI-detected synovitis of grade 1 or more in at least one joint. They excluded patients with concomitant rheumatic disease, gout, psoriasis, positive rheumatoid factor or anti-cyclic citrullinated peptides, or elevated inflammatory markers (erythrocyte sedimentation rate or C-reactive protein), as well as those with contraindication to methotrexate or MRI.

The trials’ 97 participants were assigned 1:1 to MTX or placebo using block randomization. The MTX group started on oral MTX 10 mg weekly for the first 4 weeks, followed by 20 mg weekly for the remainder of the study. Participants took folic acid 5 mg once a day to reduce risk of MTX-related side effects.

The mean age of the participants was 61 years, with 70% female. Baseline characteristics were generally well-balanced, except for higher mean BMI in the MTX group. At 6 months, the MTX group had a greater reduction in mean VAS pain than the placebo group (–15.2 mm vs. –7.7 mm; adjusted between-group difference, –9.9 mm). The minimally clinically important difference for OA trials is a 15-mm change (out of 100) in VAS pain.

The MTX group also had greater reduction in mean Australian Canadian OA Hand Index (AUSCAN) score for pain and stiffness at 6 months, compared with placebo, but there were no differences in other secondary outcomes (mean AUSCAN, Functional Index for Hand Osteoarthritis, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, or grip strength).

MTX was well-tolerated with no serious adverse events related to treatment; only 5 of 50 participants in the MTX group and 4 of 47 in the placebo group discontinued study medication. Incidence of adverse events was similar in the two groups throughout the trial, including mild leukopenia, elevated liver enzymes, mild reduction of hemoglobin, and raised creatinine. None of the laboratory abnormalities required change in medication dosage or affected ability to continue in the study. 
 

Qualifications and considerations for MTX use

Commenting on the study, OA researcher Amanda E. Nelson, MD, MSCR, associate professor of medicine at the University of North Carolina at Chapel Hill’s Thurston Arthritis Research Center, said that its overall design was “excellent,” including appropriate masking, controls, randomization, and power and sample size calculations, contributing to “the trial’s relatively positive, although still modest, results.” Dr. Nelson was not involved with the METHODS study.

Dr. Nelson

Several factors may have contributed to the study’s success, including the broader mechanism of action of methotrexate and higher dose used, Ida K. Haugen, MD, PhD, senior researcher at Diakonhjemmet Hospital’s Center for Treatment of Rheumatic and Musculoskeletal Diseases in Oslo, Norway, told this news organization.

She noted that the MTX 20 mg/week dosage is similar to what is used in treatment of RA and may be key to better targeting inflammation.

Nicolas Tourrenc

“Furthermore, the study included individuals with hand OA and synovitis by MRI, and thus may have found the right patient population in comparison to prior studies,” Dr. Haugen said.

Dr. Cicuttini agreed, noting that “previous trials [of MTX] did not target the inflammatory phenotype of hand osteoarthritis that would be expected to respond.” In the previous randomized controlled trial of MTX in hand OA, only 29 of a total 1024 joints had synovitis, she explained. “Their inclusion criteria were individuals with severe erosive hand osteoarthritis, suggesting that this later-stage disease is less likely to respond.”

Dr. Cicuttini said that she saw no specific issues in regard to potential use of MTX in the OA population in the clinic. “The data we have, together with the large experience we have with using methotrexate and the fact that treatments for hand OA are not very effective, means that it would be reasonable to offer this to patients with hand OA and inflammation,” she said. “The level of evidence for an effect of methotrexate would need to be discussed with the patient. The discussion around the use of methotrexate would then need to proceed in the same way we discuss the use of methotrexate with patients when used for other inflammatory joint diseases, and the decision is then made with the patient.”

In contrast, Dr. Nelson expressed some concerns regarding the immediate use of MTX for this population. “Many individuals with hand OA have multiple medical comorbidities and polypharmacy, which are important when considering additional treatments, particularly those with modest benefit and potential adverse effects over the long term,” she said. “I do not think this single study provides enough evidence to suggest that all such patients should be treated with methotrexate, and more data, particularly about long-term use and optimal risk stratification, is needed.” 

While MTX use in refractory inflammatory hand OA is not yet recommended in international guidelines, Dr. Haugen believes this study supports use of MTX in this patient population. Given that MRI and ultrasound may not always be available to identify synovitis, Dr. Nelson and Dr. Haugen suggested identifying patients who may benefit through careful history and clinical examination for evidence of swollen joints. In addition, Dr. Cicuttini explained that she would not necessarily use MTX in patients with erosive OA radiographically because it may be a later stage of disease that is less likely to respond.

The authors highlighted potential limitations of the METHODS trial. They initially planned to study whether MTX reduced pain and improved radiographic progression at 2 years, but since they paused the study for 7 months during the COVID-19 pandemic, they amended the trial protocol and focused on pain reduction at 6 months as the primary endpoint instead.

Tender and swollen joint counts were initially going to be included, but this was modified given the use of virtual telemedicine visits during the pandemic. Dr. Cicuttini said that further studies are underway to identify potential subpopulations who may benefit from immunosuppression, and others are needed to determine whether MTX reduces joint damage and slows disease progression in hand OA with inflammation.

Dr. Cicuttini said her research group is interested to see whether women who develop hand OA around the time of menopause (“menopausal OA”) are a group that could benefit. Dr. Haugen noted that she is involved in a study testing MTX in erosive hand OA (the MERINO trial). 

The study was funded by a project grant from the National Health and Medical Research Council of Australia. The authors reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.

Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.

Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.

Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.

There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
 

Previous clinical trials have failed

Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.

However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.

One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.

Ron Hester

The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.

Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
 

Finding patients with ACL reconstruction with ‘bad outcomes’

Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.

When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.

“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.

The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.

A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.

Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.

“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
 

Clinical trial to test FastOA criteria

The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.

FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.

The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.

The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .

Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.

Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).

“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.

People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.

“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.

Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.

Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.

Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.

“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
 

‘We’re taking a leap’

PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.

Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.

Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.

Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.

“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.

Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.

The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.

PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.

“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.

“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.

Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.

While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.

“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.

The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.

Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
 

David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.

Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.

Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.

Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.

There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
 

Previous clinical trials have failed

Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.

However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.

One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.

Ron Hester

The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.

Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
 

Finding patients with ACL reconstruction with ‘bad outcomes’

Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.

When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.

“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.

The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.

A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.

Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.

“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
 

Clinical trial to test FastOA criteria

The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.

FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.

The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.

The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .

Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.

Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).

“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.

People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.

“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.

Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.

Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.

Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.

“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
 

‘We’re taking a leap’

PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.

Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.

Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.

Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.

“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.

Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.

The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.

PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.

“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.

“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.

Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.

While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.

“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.

The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.

Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
 

David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.

Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.

Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.

Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.

There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
 

Previous clinical trials have failed

Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.

However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.

One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.

Ron Hester

The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.

Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
 

Finding patients with ACL reconstruction with ‘bad outcomes’

Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.

When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.

“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.

The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.

A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.

Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.

“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
 

Clinical trial to test FastOA criteria

The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.

FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.

The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.

The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .

Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.

Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).

“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.

People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.

“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.

Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.

Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.

Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.

“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
 

‘We’re taking a leap’

PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.

Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.

Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.

Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.

“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.

Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.

The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.

PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.

“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.

“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.

Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.

While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.

“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.

The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.

Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
 

Certain products marketed for arthritis and pain management could contain hidden ingredients that could be harmful to consumers, according to a warning by the U.S. Food and Drug Administration.
 

Some of these products contain active ingredients found in anti-inflammatory prescription medication.

“These products may cause potentially serious side effects and may interact with medications or dietary supplements a consumer is taking,” the FDA said in a statement. “It is clear from the results of our decade of testing that retailers and distributors, including online marketplaces, do not effectively prevent these types of potentially harmful products from being sold to consumers.”

Unlike prescription medication and over-the-counter drugs such as loratadine (Claritin) or acetaminophen (Tylenol), supplements do not need FDA approval before they can be sold. Only after a complaint is made or FDA testing reveals illegal or unsafe ingredients can the FDA get involved.

From August 2013 to September 2023, the FDA identified 22 arthritis and pain products with active ingredients not disclosed on the product label. The most common hidden ingredients detected in these supplements were prescription-only corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants, said Candy Tsourounis, PharmD, a professor in the department of clinical pharmacy at the University of California, San Francisco.

Kuka Flex Forte and Reumo Flex, both promoted for joint pain and arthritis, both contain the NSAID diclofenac. Tapee Tea, a product promoted for pain relief, contains dexamethasone and piroxicam. AK Forte, also sold for joint pain and arthritis, contains diclofenac, dexamethasone, and methocarbamol not disclosed on the label.

“It is interesting that these products have hidden ingredients that are used to reduce swelling and inflammation,” Dr. Tsourounis said. “I don’t know if this was intentional, but it seems suspicious that a product marketed to reduce joint pain and inflammation contains prescription-only ingredients that are used for this purpose.”

Certain products also contained antihistamines including cyproheptadine and chlorpheniramine.

These types of products are likely targeted toward underserved and immigrant communities, added Pieter Cohen, MD, a primary care physician and an assistant professor of medicine at Harvard Medical School, Boston, who studies dietary supplements. They might be sold in mom-and-pop shops or gas stations to individuals with limited access to health care or insurance, he noted.

The FDA warned that this list included “only a small fraction of the potentially dangerous products marketed to consumers online and in stores. Even if a product is not included in this list, consumers should exercise caution before using these types of arthritis and pain management products.”
 

Advising patients

Research suggests that most patients do not tell doctors about the supplements they are taking, and often, clinicians do not ask, said Dr. Cohen. “Most of the time it’s a total black box – we don’t know what’s going on,” he added.

He advised raising the subject of supplements in a very nonjudgmental way, particularly when treating patients in marginalized and immigrant communities. One approach he suggested was first mentioning that other patients in your care dealing with joint pain have bought remedies locally or have tried treatments that friends recommend. You can then ask a patient about their own use, framing it as a way to better help with treatment decisions.

Once a clinician understands what their patient is taking, they can then give advice and discuss if a product is safe to combine with prescription drugs, Dr. Cohen said. “If they come down too hard, I think the patients will just clam up and not talk about it anymore,” he said.

If a patient begins to experience side effects or gets sick, a clinician will already be informed of what their patient is taking and can ask that patient to bring the product or supplement in, so they can look over the product together, Dr. Cohen noted. Any side effects or other adverse events potentially related to the use of these products should then be reported to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
 

Tips for safe shopping

To make sure supplements and other over-the-counter products are safe to use, Dr. Tsourounis recommends that consumers:

• Buy products from well-known retailers like Target or large pharmacies like CVS or Walgreens.
• Avoid buying products with labels in another language that you cannot read or products with no drug label.
• Be cautious of buying products online or from other countries.
• Look up suspicious products on the FDA’s health fraud database.
• Be wary of any product that offers miracle cures or relies on personal testimonies without evidence.

In general, do not base purchasing decisions on any health claims on a product label because companies selling supplements making these claims “don’t have to have any clinical data to back them up,” Dr. Cohen said.

Dr. Cohen also recommends sticking with individual ingredients. “If you want echinacea, buy echinacea. Don’t buy a complicated mix that is supposed to be good for arthritis with 10 different botanical [ingredients]. That’s more likely to run [you] into trouble,” he said.

Last, Dr. Cohen recommended buying supplements that are certified by NSF International or United States Pharmacopeia, both respected third-party testing organizations. “If it has an NSF International or USP stamp, that gives us more certainty that what’s in the bottle is going to be what’s listed on label,” he said.

Dr. Tsourounis noted that if you are skeptical of a product, you can also try calling the manufacturer number on the product label.

“I always encourage people to call that number to see if somebody answers,” she said. “Sometimes, you can tell a lot about that company just by calling that number.”

Dr. Cohen has received research support from the Consumers Union and PEW Charitable Trusts and royalties from UpToDate. He has collaborated in research with NSF International. Dr. Tsourounis disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Certain products marketed for arthritis and pain management could contain hidden ingredients that could be harmful to consumers, according to a warning by the U.S. Food and Drug Administration.
 

Some of these products contain active ingredients found in anti-inflammatory prescription medication.

“These products may cause potentially serious side effects and may interact with medications or dietary supplements a consumer is taking,” the FDA said in a statement. “It is clear from the results of our decade of testing that retailers and distributors, including online marketplaces, do not effectively prevent these types of potentially harmful products from being sold to consumers.”

Unlike prescription medication and over-the-counter drugs such as loratadine (Claritin) or acetaminophen (Tylenol), supplements do not need FDA approval before they can be sold. Only after a complaint is made or FDA testing reveals illegal or unsafe ingredients can the FDA get involved.

From August 2013 to September 2023, the FDA identified 22 arthritis and pain products with active ingredients not disclosed on the product label. The most common hidden ingredients detected in these supplements were prescription-only corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants, said Candy Tsourounis, PharmD, a professor in the department of clinical pharmacy at the University of California, San Francisco.

Kuka Flex Forte and Reumo Flex, both promoted for joint pain and arthritis, both contain the NSAID diclofenac. Tapee Tea, a product promoted for pain relief, contains dexamethasone and piroxicam. AK Forte, also sold for joint pain and arthritis, contains diclofenac, dexamethasone, and methocarbamol not disclosed on the label.

“It is interesting that these products have hidden ingredients that are used to reduce swelling and inflammation,” Dr. Tsourounis said. “I don’t know if this was intentional, but it seems suspicious that a product marketed to reduce joint pain and inflammation contains prescription-only ingredients that are used for this purpose.”

Certain products also contained antihistamines including cyproheptadine and chlorpheniramine.

These types of products are likely targeted toward underserved and immigrant communities, added Pieter Cohen, MD, a primary care physician and an assistant professor of medicine at Harvard Medical School, Boston, who studies dietary supplements. They might be sold in mom-and-pop shops or gas stations to individuals with limited access to health care or insurance, he noted.

The FDA warned that this list included “only a small fraction of the potentially dangerous products marketed to consumers online and in stores. Even if a product is not included in this list, consumers should exercise caution before using these types of arthritis and pain management products.”
 

Advising patients

Research suggests that most patients do not tell doctors about the supplements they are taking, and often, clinicians do not ask, said Dr. Cohen. “Most of the time it’s a total black box – we don’t know what’s going on,” he added.

He advised raising the subject of supplements in a very nonjudgmental way, particularly when treating patients in marginalized and immigrant communities. One approach he suggested was first mentioning that other patients in your care dealing with joint pain have bought remedies locally or have tried treatments that friends recommend. You can then ask a patient about their own use, framing it as a way to better help with treatment decisions.

Once a clinician understands what their patient is taking, they can then give advice and discuss if a product is safe to combine with prescription drugs, Dr. Cohen said. “If they come down too hard, I think the patients will just clam up and not talk about it anymore,” he said.

If a patient begins to experience side effects or gets sick, a clinician will already be informed of what their patient is taking and can ask that patient to bring the product or supplement in, so they can look over the product together, Dr. Cohen noted. Any side effects or other adverse events potentially related to the use of these products should then be reported to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
 

Tips for safe shopping

To make sure supplements and other over-the-counter products are safe to use, Dr. Tsourounis recommends that consumers:

• Buy products from well-known retailers like Target or large pharmacies like CVS or Walgreens.
• Avoid buying products with labels in another language that you cannot read or products with no drug label.
• Be cautious of buying products online or from other countries.
• Look up suspicious products on the FDA’s health fraud database.
• Be wary of any product that offers miracle cures or relies on personal testimonies without evidence.

In general, do not base purchasing decisions on any health claims on a product label because companies selling supplements making these claims “don’t have to have any clinical data to back them up,” Dr. Cohen said.

Dr. Cohen also recommends sticking with individual ingredients. “If you want echinacea, buy echinacea. Don’t buy a complicated mix that is supposed to be good for arthritis with 10 different botanical [ingredients]. That’s more likely to run [you] into trouble,” he said.

Last, Dr. Cohen recommended buying supplements that are certified by NSF International or United States Pharmacopeia, both respected third-party testing organizations. “If it has an NSF International or USP stamp, that gives us more certainty that what’s in the bottle is going to be what’s listed on label,” he said.

Dr. Tsourounis noted that if you are skeptical of a product, you can also try calling the manufacturer number on the product label.

“I always encourage people to call that number to see if somebody answers,” she said. “Sometimes, you can tell a lot about that company just by calling that number.”

Dr. Cohen has received research support from the Consumers Union and PEW Charitable Trusts and royalties from UpToDate. He has collaborated in research with NSF International. Dr. Tsourounis disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Certain products marketed for arthritis and pain management could contain hidden ingredients that could be harmful to consumers, according to a warning by the U.S. Food and Drug Administration.
 

Some of these products contain active ingredients found in anti-inflammatory prescription medication.

“These products may cause potentially serious side effects and may interact with medications or dietary supplements a consumer is taking,” the FDA said in a statement. “It is clear from the results of our decade of testing that retailers and distributors, including online marketplaces, do not effectively prevent these types of potentially harmful products from being sold to consumers.”

Unlike prescription medication and over-the-counter drugs such as loratadine (Claritin) or acetaminophen (Tylenol), supplements do not need FDA approval before they can be sold. Only after a complaint is made or FDA testing reveals illegal or unsafe ingredients can the FDA get involved.

From August 2013 to September 2023, the FDA identified 22 arthritis and pain products with active ingredients not disclosed on the product label. The most common hidden ingredients detected in these supplements were prescription-only corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants, said Candy Tsourounis, PharmD, a professor in the department of clinical pharmacy at the University of California, San Francisco.

Kuka Flex Forte and Reumo Flex, both promoted for joint pain and arthritis, both contain the NSAID diclofenac. Tapee Tea, a product promoted for pain relief, contains dexamethasone and piroxicam. AK Forte, also sold for joint pain and arthritis, contains diclofenac, dexamethasone, and methocarbamol not disclosed on the label.

“It is interesting that these products have hidden ingredients that are used to reduce swelling and inflammation,” Dr. Tsourounis said. “I don’t know if this was intentional, but it seems suspicious that a product marketed to reduce joint pain and inflammation contains prescription-only ingredients that are used for this purpose.”

Certain products also contained antihistamines including cyproheptadine and chlorpheniramine.

These types of products are likely targeted toward underserved and immigrant communities, added Pieter Cohen, MD, a primary care physician and an assistant professor of medicine at Harvard Medical School, Boston, who studies dietary supplements. They might be sold in mom-and-pop shops or gas stations to individuals with limited access to health care or insurance, he noted.

The FDA warned that this list included “only a small fraction of the potentially dangerous products marketed to consumers online and in stores. Even if a product is not included in this list, consumers should exercise caution before using these types of arthritis and pain management products.”
 

Advising patients

Research suggests that most patients do not tell doctors about the supplements they are taking, and often, clinicians do not ask, said Dr. Cohen. “Most of the time it’s a total black box – we don’t know what’s going on,” he added.

He advised raising the subject of supplements in a very nonjudgmental way, particularly when treating patients in marginalized and immigrant communities. One approach he suggested was first mentioning that other patients in your care dealing with joint pain have bought remedies locally or have tried treatments that friends recommend. You can then ask a patient about their own use, framing it as a way to better help with treatment decisions.

Once a clinician understands what their patient is taking, they can then give advice and discuss if a product is safe to combine with prescription drugs, Dr. Cohen said. “If they come down too hard, I think the patients will just clam up and not talk about it anymore,” he said.

If a patient begins to experience side effects or gets sick, a clinician will already be informed of what their patient is taking and can ask that patient to bring the product or supplement in, so they can look over the product together, Dr. Cohen noted. Any side effects or other adverse events potentially related to the use of these products should then be reported to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
 

Tips for safe shopping

To make sure supplements and other over-the-counter products are safe to use, Dr. Tsourounis recommends that consumers:

• Buy products from well-known retailers like Target or large pharmacies like CVS or Walgreens.
• Avoid buying products with labels in another language that you cannot read or products with no drug label.
• Be cautious of buying products online or from other countries.
• Look up suspicious products on the FDA’s health fraud database.
• Be wary of any product that offers miracle cures or relies on personal testimonies without evidence.

In general, do not base purchasing decisions on any health claims on a product label because companies selling supplements making these claims “don’t have to have any clinical data to back them up,” Dr. Cohen said.

Dr. Cohen also recommends sticking with individual ingredients. “If you want echinacea, buy echinacea. Don’t buy a complicated mix that is supposed to be good for arthritis with 10 different botanical [ingredients]. That’s more likely to run [you] into trouble,” he said.

Last, Dr. Cohen recommended buying supplements that are certified by NSF International or United States Pharmacopeia, both respected third-party testing organizations. “If it has an NSF International or USP stamp, that gives us more certainty that what’s in the bottle is going to be what’s listed on label,” he said.

Dr. Tsourounis noted that if you are skeptical of a product, you can also try calling the manufacturer number on the product label.

“I always encourage people to call that number to see if somebody answers,” she said. “Sometimes, you can tell a lot about that company just by calling that number.”

Dr. Cohen has received research support from the Consumers Union and PEW Charitable Trusts and royalties from UpToDate. He has collaborated in research with NSF International. Dr. Tsourounis disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

WASHINGTON – The entire video clip is just 15 seconds — 15 seconds that went viral and temporarily upended the entire life and disrupted the medical practice of Nicole Baldwin, MD, a pediatrician in Cincinnati, Ohio, in January 2020. At the annual meeting of the American Academy of Pediatrics, Dr. Baldwin told attendees how her pro-vaccine TikTok video led a horde of anti-vaccine activists to swarm her social media profiles across multiple platforms, leave one-star reviews with false stories about her medical practice on various doctor review sites, and personally threaten her.

The initial response to the video was positive, with 50,000 views in the first 24 hours after the video was posted and more than 1.5 million views the next day. But 2 days after the video was posted, an organized attack that originated on Facebook required Dr. Baldwin to enlist the help of 16 volunteers, working 24/7 for a week, to help ban and block more than 6,000 users on Facebook, Instagram, and TikTok. Just 4 days after she’d posted the video, Dr. Baldwin was reporting personal threats to the police and had begun contacting sites such as Yelp, Google, Healthgrades, Vitals, RateMDs, and WebMD so they could start removing false reviews about her practice.

Today, years after those 2 exhausting, intense weeks of attacks, Dr. Baldwin has found two silver linings in the experience: More people have found her profiles, allowing her to share evidence-based information with an even wider audience, and she can now help other physicians protect themselves and reduce the risk of similar attacks, or at least know how to respond to them if they occur. Dr. Baldwin shared a wealth of tips and resources during her lecture to help pediatricians prepare ahead for the possibility that they will be targeted next, whether the issue is vaccines or another topic.
 

Online risks and benefits

A Pew survey of U.S. adults in September 2020 found that 41% have personally experienced online harassment, including a quarter of Americans who have experienced severe harassment. More than half of respondents said online harassment and bullying is a major problem – and that was a poll of the entire population, not even just physicians and scientists.

“Now, these numbers would be higher,” Dr. Baldwin said. “A lot has changed in the past 3 years, and the landscape is very different.”

The pandemic contributed to those changes to the landscape, including an increase in harassment of doctors and researchers. A June 2023 study revealed that two-thirds of 359 respondents in an online survey reported harassment on social media, a substantial number even after accounting for selection bias in the individuals who chose to respond to the survey. Although most of the attacks (88%) resulted from the respondent’s advocacy online, nearly half the attacks (45%) were gender based, 27% were based on race/ethnicity, and 13% were based on sexual orientation.

While hateful comments are likely the most common type of online harassment, other types can involve sharing or tagging your profile, creating fake profiles to misrepresent you, fake reviews of your practice, harassing phone calls and hate mail at your office, and doxxing, in which someone online widely shares your personal address, phone number, email, or other contact information.

Despite the risks of all these forms of harassment, Dr. Baldwin emphasized the value of doctors having a social media presence given how much misinformation thrives online. For example, a recent report from the Kaiser Family Foundation revealed how many people weren’t sure whether certain health misinformation claims were true or false. Barely a third of people were sure that COVID-19 vaccines had not caused thousands of deaths in healthy people, and only 22% of people were sure that ivermectin is not an effective treatment for COVID.

“There is so much that we need to be doing and working in these spaces to put evidence-based content out there so that people are not finding all of this crap from everybody else,” Dr. Baldwin said. Having an online presence is particularly important given that the public still has high levels of trust in their doctors, she added.

“They trust their physician, and you may not be their physician online, but I will tell you from experience, when you build a community of followers, you become that trusted source of information for them, and it is so important,” Dr. Baldwin said. “There is room for everybody in this space, and we need all of you.”
 

Proactive steps for protection

Dr. Baldwin then went through the details of what people should do now to make things easier in the event of an attack later. “The best defense is a good offense,” Dr. Baldwin said, “so make sure all of your accounts are secure.”

She recommended the following steps:

• Use two-factor authentication for all of your logins.
• Use strong, unique passwords for all of your logins.
• Use strong privacy settings on all of your private social media profiles, such as making sure photos are not visible on your personal Facebook account.
• Claim your Google profile and Yelp business profile.
• Claim your doctor and/or business profile on all of the medical review sites where you have one, including Google, Healthgrades, Vitals, RateMDs, and WebMD.

For doctors who are attacked specifically because of pro-vaccine advocacy, Dr. Baldwin recommended contacting Shots Heard Round The World, a site that was created by a physician whose practice was attacked by anti-vaccine activists. The site also has a toolkit that anyone can download for tips on preparing ahead for possible attacks and what to do if you are attacked.

Dr. Baldwin then reviewed how to set up different social media profiles to automatically hide certain comments, including comments with words commonly used by online harassers and trolls:

• Sheep
• Sheeple
• Pharma
• Shill
• Die
• Psychopath
• Clown
• Various curse words
• The clown emoji

In Instagram, go to “Settings and privacy —> Hidden Words” for options on hiding offensive comments and messages and for managing custom words and phrases that should be automatically hidden.

On Facebook, go to “Professional dashboard —> Moderation Assist,” where you can add or edit criteria to automatically hide comments on your Facebook page. In addition to hiding comments with certain keywords, you can hide comments from new accounts, accounts without profile photos, or accounts with no friends or followers.

On TikTok, click the three-line menu icon in the upper right, and choose “Privacy —> Comments —> Filter keywords.”

On the platform formerly known as Twitter, go to “Settings and privacy —> Privacy and safety —> Mute and block —> Muted words.”

On YouTube, under “Manage your community & comments,” select “Learn about comment settings.”

Dr. Baldwin did not discourage doctors from posting about controversial topics, but she said it’s important to know what they are so that you can be prepared for the possibility that a post about one of these topics could lead to online harassment. These hot button topics include vaccines, firearm safety, gender-affirming care, reproductive choice, safe sleep/bedsharing, breastfeeding, and COVID masks.

If you do post on one of these and suspect it could result in harassment, Dr. Baldwin recommends turning on your notifications so you know when attacks begin, alerting your office and call center staff if you think they might receive calls, and, when possible, post your content at a time when you’re more likely to be able to monitor the post. She acknowledged that this last tip isn’t always relevant since attacks can take a few days to start or gain steam.
 

Defending yourself in an attack

Even after taking all these precautions, it’s not possible to altogether prevent an attack from happening, so Dr. Baldwin provided suggestions on what to do if one occurs, starting with taking a deep breath.

“If you are attacked, first of all, please remain calm, which is a lot easier said than done,” she said. “But know that this too shall pass. These things do come to an end.”

She advises you to get help if you need it, enlisting friends or colleagues to help with moderation and banning/blocking. If necessary, alert your employer to the attack, as attackers may contact your employer. Some people may opt to turn off comments on their post, but doing so “is a really personal decision,” she said. It’s okay to turn off comments if you don’t have the bandwidth or help to deal with them.

However, Dr. Baldwin said she never turns off comments because she wants to be able to ban and block people to reduce the likelihood of a future attack from them, and each comment brings the post higher in the algorithm so that more people are able to see the original content. “So sometimes these things are actually a blessing in disguise,” she said.

If you do have comments turned on, take screenshots of the most egregious or threatening ones and then report them and ban/block them. The screenshots are evidence since blocking will remove the comment.

“Take breaks when you need to,” she said. “Don’t stay up all night” since there are only going to be more in the morning, and if you’re using keywords to help hide many of these comments, that will hide them from your followers while you’re away. She also advised monitoring your online reviews at doctor/practice review sites so you know whether you’re receiving spurious reviews that need to be removed.

Dr. Baldwin also addressed how to handle trolls, the people online who intentionally antagonize others with inflammatory, irrelevant, offensive, or otherwise disruptive comments or content. The No. 1 rule is not to engage – “Don’t feed the trolls” – but Dr. Baldwin acknowledged that she can find that difficult sometimes. So she uses kindness or humor to defuse them or calls them out on their inaccurate information and then thanks them for their engagement. Don’t forget that you are in charge of your own page, so any complaints about “censorship” or infringing “free speech” aren’t relevant.

If the comments are growing out of control and you’re unable to manage them, multiple social media platforms have options for limited interactions or who can comment on your page.

On Instagram under “Settings and privacy,” check out “Limited interactions,” “Comments —> Allow comments from,” and “Tags and mentions” to see ways you can limit who is able to comment, tag or mention your account. If you need a complete break, you can turn off commenting by clicking the three dots in the upper right corner of the post, or make your account temporarily private under “Settings and privacy —> Account privacy.”

On Facebook, click the three dots in the upper right corner of posts to select “Who can comment on your post?” Also, under “Settings —> Privacy —> Your Activity,” you can adjust who sees your future posts. Again, if things are out of control, you can temporarily deactivate your page under “Settings —> Privacy —> Facebook Page information.”

On TikTok, click the three lines in the upper right corner of your profile and select “Privacy —> Comments” to adjust who can comment and to filter comments. Again, you can make your account private under “Settings and privacy —> Privacy —> Private account.”

On the platform formerly known as Twitter, click the three dots in the upper right corner of the tweet to change who can reply to the tweet. If you select “Only people you mentioned,” then no one can reply if you did not mention anyone. You can control tagging under “Settings and privacy —> Privacy and safety —> Audience and tagging.”

If you or your practice receive false reviews on review sites, report the reviews and alert the rating site when you can. In the meantime, lock down your private social media accounts and ensure that no photos of your family are publicly available.
 

Social media self-care

Dr. Baldwin acknowledged that experiencing a social media attack can be intense and even frightening, but it’s rare and outweighed by the “hundreds and hundreds and hundreds of positive comments all the time.” She also reminded attendees that being on social media doesn’t mean being there all the time.

“Over time, my use of social media has certainly changed. It ebbs and flows,” she said. “There are times when I have a lot of bandwidth and I’m posting a lot, and then I actually have had some struggles with my own mental health, with some anxiety and mild depression, so I took a break from social media for a while. When I came back, I posted about my mental health struggles, and you wouldn’t believe how many people were so appreciative of that.”
 

Accurate information from a trusted source

Ultimately, Dr. Baldwin sees her work online as an extension of her work educating patients.

“This is where our patients are. They are in your office for maybe 10-15 minutes maybe once a year, but they are on these platforms every single day for hours,” she said. “They need to see this information from medical professionals because there are random people out there that are telling them [misinformation].”

Elizabeth Murray, DO, MBA, an emergency medicine pediatrician at Golisano Children’s Hospital at the University of Rochester, agreed that there’s substantial value in doctors sharing accurate information online.

“Disinformation and misinformation is rampant, and at the end of the day, we know the facts,” Dr. Murray said. “We know what parents want to hear and what they want to learn about, so we need to share that information and get the facts out there.”

Dr. Murray found the session very helpful because there’s so much to learn across different social media platforms and it can feel overwhelming if you aren’t familiar with the tools.

“Social media is always going to be here. We need to learn to live with all of these platforms,” Dr. Murray said. “That’s a skill set. We need to learn the skills and teach our kids the skill set. You never really know what you might put out there that, in your mind is innocent or very science-based, that for whatever reason somebody might take issue with. You might as well be ready because we’re all about prevention in pediatrics.”

There were no funders for the presentation. Dr. Baldwin and Dr. Murray had no disclosures.

WASHINGTON – The entire video clip is just 15 seconds — 15 seconds that went viral and temporarily upended the entire life and disrupted the medical practice of Nicole Baldwin, MD, a pediatrician in Cincinnati, Ohio, in January 2020. At the annual meeting of the American Academy of Pediatrics, Dr. Baldwin told attendees how her pro-vaccine TikTok video led a horde of anti-vaccine activists to swarm her social media profiles across multiple platforms, leave one-star reviews with false stories about her medical practice on various doctor review sites, and personally threaten her.

The initial response to the video was positive, with 50,000 views in the first 24 hours after the video was posted and more than 1.5 million views the next day. But 2 days after the video was posted, an organized attack that originated on Facebook required Dr. Baldwin to enlist the help of 16 volunteers, working 24/7 for a week, to help ban and block more than 6,000 users on Facebook, Instagram, and TikTok. Just 4 days after she’d posted the video, Dr. Baldwin was reporting personal threats to the police and had begun contacting sites such as Yelp, Google, Healthgrades, Vitals, RateMDs, and WebMD so they could start removing false reviews about her practice.

Today, years after those 2 exhausting, intense weeks of attacks, Dr. Baldwin has found two silver linings in the experience: More people have found her profiles, allowing her to share evidence-based information with an even wider audience, and she can now help other physicians protect themselves and reduce the risk of similar attacks, or at least know how to respond to them if they occur. Dr. Baldwin shared a wealth of tips and resources during her lecture to help pediatricians prepare ahead for the possibility that they will be targeted next, whether the issue is vaccines or another topic.
 

Online risks and benefits

A Pew survey of U.S. adults in September 2020 found that 41% have personally experienced online harassment, including a quarter of Americans who have experienced severe harassment. More than half of respondents said online harassment and bullying is a major problem – and that was a poll of the entire population, not even just physicians and scientists.

“Now, these numbers would be higher,” Dr. Baldwin said. “A lot has changed in the past 3 years, and the landscape is very different.”

The pandemic contributed to those changes to the landscape, including an increase in harassment of doctors and researchers. A June 2023 study revealed that two-thirds of 359 respondents in an online survey reported harassment on social media, a substantial number even after accounting for selection bias in the individuals who chose to respond to the survey. Although most of the attacks (88%) resulted from the respondent’s advocacy online, nearly half the attacks (45%) were gender based, 27% were based on race/ethnicity, and 13% were based on sexual orientation.

While hateful comments are likely the most common type of online harassment, other types can involve sharing or tagging your profile, creating fake profiles to misrepresent you, fake reviews of your practice, harassing phone calls and hate mail at your office, and doxxing, in which someone online widely shares your personal address, phone number, email, or other contact information.

Despite the risks of all these forms of harassment, Dr. Baldwin emphasized the value of doctors having a social media presence given how much misinformation thrives online. For example, a recent report from the Kaiser Family Foundation revealed how many people weren’t sure whether certain health misinformation claims were true or false. Barely a third of people were sure that COVID-19 vaccines had not caused thousands of deaths in healthy people, and only 22% of people were sure that ivermectin is not an effective treatment for COVID.

“There is so much that we need to be doing and working in these spaces to put evidence-based content out there so that people are not finding all of this crap from everybody else,” Dr. Baldwin said. Having an online presence is particularly important given that the public still has high levels of trust in their doctors, she added.

“They trust their physician, and you may not be their physician online, but I will tell you from experience, when you build a community of followers, you become that trusted source of information for them, and it is so important,” Dr. Baldwin said. “There is room for everybody in this space, and we need all of you.”
 

Proactive steps for protection

Dr. Baldwin then went through the details of what people should do now to make things easier in the event of an attack later. “The best defense is a good offense,” Dr. Baldwin said, “so make sure all of your accounts are secure.”

She recommended the following steps:

• Use two-factor authentication for all of your logins.
• Use strong, unique passwords for all of your logins.
• Use strong privacy settings on all of your private social media profiles, such as making sure photos are not visible on your personal Facebook account.
• Claim your Google profile and Yelp business profile.
• Claim your doctor and/or business profile on all of the medical review sites where you have one, including Google, Healthgrades, Vitals, RateMDs, and WebMD.

For doctors who are attacked specifically because of pro-vaccine advocacy, Dr. Baldwin recommended contacting Shots Heard Round The World, a site that was created by a physician whose practice was attacked by anti-vaccine activists. The site also has a toolkit that anyone can download for tips on preparing ahead for possible attacks and what to do if you are attacked.

Dr. Baldwin then reviewed how to set up different social media profiles to automatically hide certain comments, including comments with words commonly used by online harassers and trolls:

• Sheep
• Sheeple
• Pharma
• Shill
• Die
• Psychopath
• Clown
• Various curse words
• The clown emoji

In Instagram, go to “Settings and privacy —> Hidden Words” for options on hiding offensive comments and messages and for managing custom words and phrases that should be automatically hidden.

On Facebook, go to “Professional dashboard —> Moderation Assist,” where you can add or edit criteria to automatically hide comments on your Facebook page. In addition to hiding comments with certain keywords, you can hide comments from new accounts, accounts without profile photos, or accounts with no friends or followers.

On TikTok, click the three-line menu icon in the upper right, and choose “Privacy —> Comments —> Filter keywords.”

On the platform formerly known as Twitter, go to “Settings and privacy —> Privacy and safety —> Mute and block —> Muted words.”

On YouTube, under “Manage your community & comments,” select “Learn about comment settings.”

Dr. Baldwin did not discourage doctors from posting about controversial topics, but she said it’s important to know what they are so that you can be prepared for the possibility that a post about one of these topics could lead to online harassment. These hot button topics include vaccines, firearm safety, gender-affirming care, reproductive choice, safe sleep/bedsharing, breastfeeding, and COVID masks.

If you do post on one of these and suspect it could result in harassment, Dr. Baldwin recommends turning on your notifications so you know when attacks begin, alerting your office and call center staff if you think they might receive calls, and, when possible, post your content at a time when you’re more likely to be able to monitor the post. She acknowledged that this last tip isn’t always relevant since attacks can take a few days to start or gain steam.
 

Defending yourself in an attack

Even after taking all these precautions, it’s not possible to altogether prevent an attack from happening, so Dr. Baldwin provided suggestions on what to do if one occurs, starting with taking a deep breath.

“If you are attacked, first of all, please remain calm, which is a lot easier said than done,” she said. “But know that this too shall pass. These things do come to an end.”

She advises you to get help if you need it, enlisting friends or colleagues to help with moderation and banning/blocking. If necessary, alert your employer to the attack, as attackers may contact your employer. Some people may opt to turn off comments on their post, but doing so “is a really personal decision,” she said. It’s okay to turn off comments if you don’t have the bandwidth or help to deal with them.

However, Dr. Baldwin said she never turns off comments because she wants to be able to ban and block people to reduce the likelihood of a future attack from them, and each comment brings the post higher in the algorithm so that more people are able to see the original content. “So sometimes these things are actually a blessing in disguise,” she said.

If you do have comments turned on, take screenshots of the most egregious or threatening ones and then report them and ban/block them. The screenshots are evidence since blocking will remove the comment.

“Take breaks when you need to,” she said. “Don’t stay up all night” since there are only going to be more in the morning, and if you’re using keywords to help hide many of these comments, that will hide them from your followers while you’re away. She also advised monitoring your online reviews at doctor/practice review sites so you know whether you’re receiving spurious reviews that need to be removed.

Dr. Baldwin also addressed how to handle trolls, the people online who intentionally antagonize others with inflammatory, irrelevant, offensive, or otherwise disruptive comments or content. The No. 1 rule is not to engage – “Don’t feed the trolls” – but Dr. Baldwin acknowledged that she can find that difficult sometimes. So she uses kindness or humor to defuse them or calls them out on their inaccurate information and then thanks them for their engagement. Don’t forget that you are in charge of your own page, so any complaints about “censorship” or infringing “free speech” aren’t relevant.

If the comments are growing out of control and you’re unable to manage them, multiple social media platforms have options for limited interactions or who can comment on your page.

On Instagram under “Settings and privacy,” check out “Limited interactions,” “Comments —> Allow comments from,” and “Tags and mentions” to see ways you can limit who is able to comment, tag or mention your account. If you need a complete break, you can turn off commenting by clicking the three dots in the upper right corner of the post, or make your account temporarily private under “Settings and privacy —> Account privacy.”

On Facebook, click the three dots in the upper right corner of posts to select “Who can comment on your post?” Also, under “Settings —> Privacy —> Your Activity,” you can adjust who sees your future posts. Again, if things are out of control, you can temporarily deactivate your page under “Settings —> Privacy —> Facebook Page information.”

On TikTok, click the three lines in the upper right corner of your profile and select “Privacy —> Comments” to adjust who can comment and to filter comments. Again, you can make your account private under “Settings and privacy —> Privacy —> Private account.”

On the platform formerly known as Twitter, click the three dots in the upper right corner of the tweet to change who can reply to the tweet. If you select “Only people you mentioned,” then no one can reply if you did not mention anyone. You can control tagging under “Settings and privacy —> Privacy and safety —> Audience and tagging.”

If you or your practice receive false reviews on review sites, report the reviews and alert the rating site when you can. In the meantime, lock down your private social media accounts and ensure that no photos of your family are publicly available.
 

Social media self-care

Dr. Baldwin acknowledged that experiencing a social media attack can be intense and even frightening, but it’s rare and outweighed by the “hundreds and hundreds and hundreds of positive comments all the time.” She also reminded attendees that being on social media doesn’t mean being there all the time.

“Over time, my use of social media has certainly changed. It ebbs and flows,” she said. “There are times when I have a lot of bandwidth and I’m posting a lot, and then I actually have had some struggles with my own mental health, with some anxiety and mild depression, so I took a break from social media for a while. When I came back, I posted about my mental health struggles, and you wouldn’t believe how many people were so appreciative of that.”
 

Accurate information from a trusted source

Ultimately, Dr. Baldwin sees her work online as an extension of her work educating patients.

“This is where our patients are. They are in your office for maybe 10-15 minutes maybe once a year, but they are on these platforms every single day for hours,” she said. “They need to see this information from medical professionals because there are random people out there that are telling them [misinformation].”

Elizabeth Murray, DO, MBA, an emergency medicine pediatrician at Golisano Children’s Hospital at the University of Rochester, agreed that there’s substantial value in doctors sharing accurate information online.

“Disinformation and misinformation is rampant, and at the end of the day, we know the facts,” Dr. Murray said. “We know what parents want to hear and what they want to learn about, so we need to share that information and get the facts out there.”

Dr. Murray found the session very helpful because there’s so much to learn across different social media platforms and it can feel overwhelming if you aren’t familiar with the tools.

“Social media is always going to be here. We need to learn to live with all of these platforms,” Dr. Murray said. “That’s a skill set. We need to learn the skills and teach our kids the skill set. You never really know what you might put out there that, in your mind is innocent or very science-based, that for whatever reason somebody might take issue with. You might as well be ready because we’re all about prevention in pediatrics.”

There were no funders for the presentation. Dr. Baldwin and Dr. Murray had no disclosures.

WASHINGTON – The entire video clip is just 15 seconds — 15 seconds that went viral and temporarily upended the entire life and disrupted the medical practice of Nicole Baldwin, MD, a pediatrician in Cincinnati, Ohio, in January 2020. At the annual meeting of the American Academy of Pediatrics, Dr. Baldwin told attendees how her pro-vaccine TikTok video led a horde of anti-vaccine activists to swarm her social media profiles across multiple platforms, leave one-star reviews with false stories about her medical practice on various doctor review sites, and personally threaten her.

The initial response to the video was positive, with 50,000 views in the first 24 hours after the video was posted and more than 1.5 million views the next day. But 2 days after the video was posted, an organized attack that originated on Facebook required Dr. Baldwin to enlist the help of 16 volunteers, working 24/7 for a week, to help ban and block more than 6,000 users on Facebook, Instagram, and TikTok. Just 4 days after she’d posted the video, Dr. Baldwin was reporting personal threats to the police and had begun contacting sites such as Yelp, Google, Healthgrades, Vitals, RateMDs, and WebMD so they could start removing false reviews about her practice.

Today, years after those 2 exhausting, intense weeks of attacks, Dr. Baldwin has found two silver linings in the experience: More people have found her profiles, allowing her to share evidence-based information with an even wider audience, and she can now help other physicians protect themselves and reduce the risk of similar attacks, or at least know how to respond to them if they occur. Dr. Baldwin shared a wealth of tips and resources during her lecture to help pediatricians prepare ahead for the possibility that they will be targeted next, whether the issue is vaccines or another topic.
 

Online risks and benefits

A Pew survey of U.S. adults in September 2020 found that 41% have personally experienced online harassment, including a quarter of Americans who have experienced severe harassment. More than half of respondents said online harassment and bullying is a major problem – and that was a poll of the entire population, not even just physicians and scientists.

“Now, these numbers would be higher,” Dr. Baldwin said. “A lot has changed in the past 3 years, and the landscape is very different.”

The pandemic contributed to those changes to the landscape, including an increase in harassment of doctors and researchers. A June 2023 study revealed that two-thirds of 359 respondents in an online survey reported harassment on social media, a substantial number even after accounting for selection bias in the individuals who chose to respond to the survey. Although most of the attacks (88%) resulted from the respondent’s advocacy online, nearly half the attacks (45%) were gender based, 27% were based on race/ethnicity, and 13% were based on sexual orientation.

While hateful comments are likely the most common type of online harassment, other types can involve sharing or tagging your profile, creating fake profiles to misrepresent you, fake reviews of your practice, harassing phone calls and hate mail at your office, and doxxing, in which someone online widely shares your personal address, phone number, email, or other contact information.

Despite the risks of all these forms of harassment, Dr. Baldwin emphasized the value of doctors having a social media presence given how much misinformation thrives online. For example, a recent report from the Kaiser Family Foundation revealed how many people weren’t sure whether certain health misinformation claims were true or false. Barely a third of people were sure that COVID-19 vaccines had not caused thousands of deaths in healthy people, and only 22% of people were sure that ivermectin is not an effective treatment for COVID.

“There is so much that we need to be doing and working in these spaces to put evidence-based content out there so that people are not finding all of this crap from everybody else,” Dr. Baldwin said. Having an online presence is particularly important given that the public still has high levels of trust in their doctors, she added.

“They trust their physician, and you may not be their physician online, but I will tell you from experience, when you build a community of followers, you become that trusted source of information for them, and it is so important,” Dr. Baldwin said. “There is room for everybody in this space, and we need all of you.”
 

Proactive steps for protection

Dr. Baldwin then went through the details of what people should do now to make things easier in the event of an attack later. “The best defense is a good offense,” Dr. Baldwin said, “so make sure all of your accounts are secure.”

She recommended the following steps:

• Use two-factor authentication for all of your logins.
• Use strong, unique passwords for all of your logins.
• Use strong privacy settings on all of your private social media profiles, such as making sure photos are not visible on your personal Facebook account.
• Claim your Google profile and Yelp business profile.
• Claim your doctor and/or business profile on all of the medical review sites where you have one, including Google, Healthgrades, Vitals, RateMDs, and WebMD.

For doctors who are attacked specifically because of pro-vaccine advocacy, Dr. Baldwin recommended contacting Shots Heard Round The World, a site that was created by a physician whose practice was attacked by anti-vaccine activists. The site also has a toolkit that anyone can download for tips on preparing ahead for possible attacks and what to do if you are attacked.

Dr. Baldwin then reviewed how to set up different social media profiles to automatically hide certain comments, including comments with words commonly used by online harassers and trolls:

• Sheep
• Sheeple
• Pharma
• Shill
• Die
• Psychopath
• Clown
• Various curse words
• The clown emoji

In Instagram, go to “Settings and privacy —> Hidden Words” for options on hiding offensive comments and messages and for managing custom words and phrases that should be automatically hidden.

On Facebook, go to “Professional dashboard —> Moderation Assist,” where you can add or edit criteria to automatically hide comments on your Facebook page. In addition to hiding comments with certain keywords, you can hide comments from new accounts, accounts without profile photos, or accounts with no friends or followers.

On TikTok, click the three-line menu icon in the upper right, and choose “Privacy —> Comments —> Filter keywords.”

On the platform formerly known as Twitter, go to “Settings and privacy —> Privacy and safety —> Mute and block —> Muted words.”

On YouTube, under “Manage your community & comments,” select “Learn about comment settings.”

Dr. Baldwin did not discourage doctors from posting about controversial topics, but she said it’s important to know what they are so that you can be prepared for the possibility that a post about one of these topics could lead to online harassment. These hot button topics include vaccines, firearm safety, gender-affirming care, reproductive choice, safe sleep/bedsharing, breastfeeding, and COVID masks.

If you do post on one of these and suspect it could result in harassment, Dr. Baldwin recommends turning on your notifications so you know when attacks begin, alerting your office and call center staff if you think they might receive calls, and, when possible, post your content at a time when you’re more likely to be able to monitor the post. She acknowledged that this last tip isn’t always relevant since attacks can take a few days to start or gain steam.
 

Defending yourself in an attack

Even after taking all these precautions, it’s not possible to altogether prevent an attack from happening, so Dr. Baldwin provided suggestions on what to do if one occurs, starting with taking a deep breath.

“If you are attacked, first of all, please remain calm, which is a lot easier said than done,” she said. “But know that this too shall pass. These things do come to an end.”

She advises you to get help if you need it, enlisting friends or colleagues to help with moderation and banning/blocking. If necessary, alert your employer to the attack, as attackers may contact your employer. Some people may opt to turn off comments on their post, but doing so “is a really personal decision,” she said. It’s okay to turn off comments if you don’t have the bandwidth or help to deal with them.

However, Dr. Baldwin said she never turns off comments because she wants to be able to ban and block people to reduce the likelihood of a future attack from them, and each comment brings the post higher in the algorithm so that more people are able to see the original content. “So sometimes these things are actually a blessing in disguise,” she said.

If you do have comments turned on, take screenshots of the most egregious or threatening ones and then report them and ban/block them. The screenshots are evidence since blocking will remove the comment.

“Take breaks when you need to,” she said. “Don’t stay up all night” since there are only going to be more in the morning, and if you’re using keywords to help hide many of these comments, that will hide them from your followers while you’re away. She also advised monitoring your online reviews at doctor/practice review sites so you know whether you’re receiving spurious reviews that need to be removed.

Dr. Baldwin also addressed how to handle trolls, the people online who intentionally antagonize others with inflammatory, irrelevant, offensive, or otherwise disruptive comments or content. The No. 1 rule is not to engage – “Don’t feed the trolls” – but Dr. Baldwin acknowledged that she can find that difficult sometimes. So she uses kindness or humor to defuse them or calls them out on their inaccurate information and then thanks them for their engagement. Don’t forget that you are in charge of your own page, so any complaints about “censorship” or infringing “free speech” aren’t relevant.

If the comments are growing out of control and you’re unable to manage them, multiple social media platforms have options for limited interactions or who can comment on your page.

On Instagram under “Settings and privacy,” check out “Limited interactions,” “Comments —> Allow comments from,” and “Tags and mentions” to see ways you can limit who is able to comment, tag or mention your account. If you need a complete break, you can turn off commenting by clicking the three dots in the upper right corner of the post, or make your account temporarily private under “Settings and privacy —> Account privacy.”

On Facebook, click the three dots in the upper right corner of posts to select “Who can comment on your post?” Also, under “Settings —> Privacy —> Your Activity,” you can adjust who sees your future posts. Again, if things are out of control, you can temporarily deactivate your page under “Settings —> Privacy —> Facebook Page information.”

On TikTok, click the three lines in the upper right corner of your profile and select “Privacy —> Comments” to adjust who can comment and to filter comments. Again, you can make your account private under “Settings and privacy —> Privacy —> Private account.”

On the platform formerly known as Twitter, click the three dots in the upper right corner of the tweet to change who can reply to the tweet. If you select “Only people you mentioned,” then no one can reply if you did not mention anyone. You can control tagging under “Settings and privacy —> Privacy and safety —> Audience and tagging.”

If you or your practice receive false reviews on review sites, report the reviews and alert the rating site when you can. In the meantime, lock down your private social media accounts and ensure that no photos of your family are publicly available.
 

Social media self-care

Dr. Baldwin acknowledged that experiencing a social media attack can be intense and even frightening, but it’s rare and outweighed by the “hundreds and hundreds and hundreds of positive comments all the time.” She also reminded attendees that being on social media doesn’t mean being there all the time.

“Over time, my use of social media has certainly changed. It ebbs and flows,” she said. “There are times when I have a lot of bandwidth and I’m posting a lot, and then I actually have had some struggles with my own mental health, with some anxiety and mild depression, so I took a break from social media for a while. When I came back, I posted about my mental health struggles, and you wouldn’t believe how many people were so appreciative of that.”
 

Accurate information from a trusted source

Ultimately, Dr. Baldwin sees her work online as an extension of her work educating patients.

“This is where our patients are. They are in your office for maybe 10-15 minutes maybe once a year, but they are on these platforms every single day for hours,” she said. “They need to see this information from medical professionals because there are random people out there that are telling them [misinformation].”

Elizabeth Murray, DO, MBA, an emergency medicine pediatrician at Golisano Children’s Hospital at the University of Rochester, agreed that there’s substantial value in doctors sharing accurate information online.

“Disinformation and misinformation is rampant, and at the end of the day, we know the facts,” Dr. Murray said. “We know what parents want to hear and what they want to learn about, so we need to share that information and get the facts out there.”

Dr. Murray found the session very helpful because there’s so much to learn across different social media platforms and it can feel overwhelming if you aren’t familiar with the tools.

“Social media is always going to be here. We need to learn to live with all of these platforms,” Dr. Murray said. “That’s a skill set. We need to learn the skills and teach our kids the skill set. You never really know what you might put out there that, in your mind is innocent or very science-based, that for whatever reason somebody might take issue with. You might as well be ready because we’re all about prevention in pediatrics.”

There were no funders for the presentation. Dr. Baldwin and Dr. Murray had no disclosures.