Lucy Hicks

The US Food and Drug Administration (FDA) has approved the biosimilar tocilizumab-aazg (Tyenne), Fresenius Kabi, the drug’s manufacturer, announced on March 7.

This is the second tocilizumab biosimilar approved by the regulatory agency and the first to be approved in both intravenous (IV) and subcutaneous formulations that are available with the reference product, Actemra, the company said in a press release. 

Wikimedia Commons/FitzColinGerald/Creative Commons License

Tocilizumab-aazg is an interleukin-6 (IL-6) receptor antagonist indicated for:

• Adults with moderate to severe rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs
• Adults with giant cell arteritis
• Patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis
• Patients aged 2 years or older with active systemic juvenile idiopathic arthritis

“Fresenius Kabi is leading the way as the first company to receive FDA approval for both IV and subcutaneous formulations of its tocilizumab biosimilar and is available in prefilled syringe, pen injector, and vial presentations,” Fabrice Romanet, senior vice president of innovation and development at Fresenius Kabi Biopharma, said in a statement.

The FDA approved the first tocilizumab biosimilar, manufactured by Biogen, in late September 2023. It is administered by IV infusion.

Tocilizumab-aazg’s approval was based on outcome and safety data from a dozen clinical studies. The drug can be administered via intravenous formulation (20 mg/mL) or subcutaneously via a single-dose 162-mg/0.9-mL prefilled syringe or single-dose prefilled autoinjector. 

The most common side effects for tocilizumab-aazg include upper respiratory tract infections, headache, hypertension, and injection site reactions. The most serious side effects include serious infections, perforation of the stomach or intestines, hepatotoxicity, and changes in certain lab results.

Tocilizumab-aazg has already launched in 10 countries, Fresenius Kabi shared in the press release, and plans to launch in additional countries in 2024 and 2025. It is not clear when tocilizumab-aazg will be made available in the United States.

“In accordance with its patent settlement agreement with Genentech, Fresenius Kabi has a license to market its tocilizumab products in the United States commencing on the license dates, which are confidential,” the company noted.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the biosimilar tocilizumab-aazg (Tyenne), Fresenius Kabi, the drug’s manufacturer, announced on March 7.

This is the second tocilizumab biosimilar approved by the regulatory agency and the first to be approved in both intravenous (IV) and subcutaneous formulations that are available with the reference product, Actemra, the company said in a press release. 

Wikimedia Commons/FitzColinGerald/Creative Commons License

Tocilizumab-aazg is an interleukin-6 (IL-6) receptor antagonist indicated for:

• Adults with moderate to severe rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs
• Adults with giant cell arteritis
• Patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis
• Patients aged 2 years or older with active systemic juvenile idiopathic arthritis

“Fresenius Kabi is leading the way as the first company to receive FDA approval for both IV and subcutaneous formulations of its tocilizumab biosimilar and is available in prefilled syringe, pen injector, and vial presentations,” Fabrice Romanet, senior vice president of innovation and development at Fresenius Kabi Biopharma, said in a statement.

The FDA approved the first tocilizumab biosimilar, manufactured by Biogen, in late September 2023. It is administered by IV infusion.

Tocilizumab-aazg’s approval was based on outcome and safety data from a dozen clinical studies. The drug can be administered via intravenous formulation (20 mg/mL) or subcutaneously via a single-dose 162-mg/0.9-mL prefilled syringe or single-dose prefilled autoinjector. 

The most common side effects for tocilizumab-aazg include upper respiratory tract infections, headache, hypertension, and injection site reactions. The most serious side effects include serious infections, perforation of the stomach or intestines, hepatotoxicity, and changes in certain lab results.

Tocilizumab-aazg has already launched in 10 countries, Fresenius Kabi shared in the press release, and plans to launch in additional countries in 2024 and 2025. It is not clear when tocilizumab-aazg will be made available in the United States.

“In accordance with its patent settlement agreement with Genentech, Fresenius Kabi has a license to market its tocilizumab products in the United States commencing on the license dates, which are confidential,” the company noted.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the biosimilar tocilizumab-aazg (Tyenne), Fresenius Kabi, the drug’s manufacturer, announced on March 7.

This is the second tocilizumab biosimilar approved by the regulatory agency and the first to be approved in both intravenous (IV) and subcutaneous formulations that are available with the reference product, Actemra, the company said in a press release. 

Wikimedia Commons/FitzColinGerald/Creative Commons License

Tocilizumab-aazg is an interleukin-6 (IL-6) receptor antagonist indicated for:

• Adults with moderate to severe rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs
• Adults with giant cell arteritis
• Patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis
• Patients aged 2 years or older with active systemic juvenile idiopathic arthritis

“Fresenius Kabi is leading the way as the first company to receive FDA approval for both IV and subcutaneous formulations of its tocilizumab biosimilar and is available in prefilled syringe, pen injector, and vial presentations,” Fabrice Romanet, senior vice president of innovation and development at Fresenius Kabi Biopharma, said in a statement.

The FDA approved the first tocilizumab biosimilar, manufactured by Biogen, in late September 2023. It is administered by IV infusion.

Tocilizumab-aazg’s approval was based on outcome and safety data from a dozen clinical studies. The drug can be administered via intravenous formulation (20 mg/mL) or subcutaneously via a single-dose 162-mg/0.9-mL prefilled syringe or single-dose prefilled autoinjector. 

The most common side effects for tocilizumab-aazg include upper respiratory tract infections, headache, hypertension, and injection site reactions. The most serious side effects include serious infections, perforation of the stomach or intestines, hepatotoxicity, and changes in certain lab results.

Tocilizumab-aazg has already launched in 10 countries, Fresenius Kabi shared in the press release, and plans to launch in additional countries in 2024 and 2025. It is not clear when tocilizumab-aazg will be made available in the United States.

“In accordance with its patent settlement agreement with Genentech, Fresenius Kabi has a license to market its tocilizumab products in the United States commencing on the license dates, which are confidential,” the company noted.
 

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with type 2 diabetes, there was no difference in risk of developing autoimmune disease if prescribed glucagon-like peptide 1 receptor agonists (GLP-1-RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors.

METHODOLOGY:

• The effect of GLP-1-RAs and SGLT2 inhibitors on autoimmune rheumatic disease (ARD) is understudied, though previous case reports and one study have hinted at increased risk.
• Researchers used administrative health data from 2014 to 2021 to identify 34,400 patients prescribed GLP-1-RAs and 83,500 patients prescribed SGLT2 inhibitors.
• They compared patients prescribed GLP-1-RAs or SGLT2 inhibitors with 68,400 patients prescribed DPP-4 inhibitors, which previous studies suggest do not increase ARD risk.
• Primary outcome was ARD incidence, defined by diagnostic codes.

TAKEAWAY:

• There were no significant differences in incident ARDs between the three groups.
• Mean follow-up time was 0.88-1.53 years.
• The hazard ratio (HR) for developing ARDs with GLP-1-RAs exposure was 0.93 (95% CI, 0.66-1.30) compared with DPP-4 inhibitors.
• The HR for developing ARDs with SGLT2 inhibitor exposure was 0.97 (95% CI, 0.76-1.24).

IN PRACTICE: 

“Extended longitudinal data are needed to assess risk and benefit with longer-term exposure,” the authors wrote.

SOURCE: 

First author Derin Karacabeyli, MD, of the University of British Columbia, Vancouver, Canada, presented the study in abstract form at the Canadian Rheumatology Association (CRA) 2024 Annual Meeting in Winnipeg on February 29.

LIMITATIONS: 

The study was observational, which could have some residual or unmeasured confounding of data. The researchers relied on diagnostic codes and the average follow-up time was short. 

DISCLOSURES:

The study was funded by the Canadian Institutes of Health Research. The authors had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with type 2 diabetes, there was no difference in risk of developing autoimmune disease if prescribed glucagon-like peptide 1 receptor agonists (GLP-1-RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors.

METHODOLOGY:

• The effect of GLP-1-RAs and SGLT2 inhibitors on autoimmune rheumatic disease (ARD) is understudied, though previous case reports and one study have hinted at increased risk.
• Researchers used administrative health data from 2014 to 2021 to identify 34,400 patients prescribed GLP-1-RAs and 83,500 patients prescribed SGLT2 inhibitors.
• They compared patients prescribed GLP-1-RAs or SGLT2 inhibitors with 68,400 patients prescribed DPP-4 inhibitors, which previous studies suggest do not increase ARD risk.
• Primary outcome was ARD incidence, defined by diagnostic codes.

TAKEAWAY:

• There were no significant differences in incident ARDs between the three groups.
• Mean follow-up time was 0.88-1.53 years.
• The hazard ratio (HR) for developing ARDs with GLP-1-RAs exposure was 0.93 (95% CI, 0.66-1.30) compared with DPP-4 inhibitors.
• The HR for developing ARDs with SGLT2 inhibitor exposure was 0.97 (95% CI, 0.76-1.24).

IN PRACTICE: 

“Extended longitudinal data are needed to assess risk and benefit with longer-term exposure,” the authors wrote.

SOURCE: 

First author Derin Karacabeyli, MD, of the University of British Columbia, Vancouver, Canada, presented the study in abstract form at the Canadian Rheumatology Association (CRA) 2024 Annual Meeting in Winnipeg on February 29.

LIMITATIONS: 

The study was observational, which could have some residual or unmeasured confounding of data. The researchers relied on diagnostic codes and the average follow-up time was short. 

DISCLOSURES:

The study was funded by the Canadian Institutes of Health Research. The authors had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with type 2 diabetes, there was no difference in risk of developing autoimmune disease if prescribed glucagon-like peptide 1 receptor agonists (GLP-1-RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors.

METHODOLOGY:

• The effect of GLP-1-RAs and SGLT2 inhibitors on autoimmune rheumatic disease (ARD) is understudied, though previous case reports and one study have hinted at increased risk.
• Researchers used administrative health data from 2014 to 2021 to identify 34,400 patients prescribed GLP-1-RAs and 83,500 patients prescribed SGLT2 inhibitors.
• They compared patients prescribed GLP-1-RAs or SGLT2 inhibitors with 68,400 patients prescribed DPP-4 inhibitors, which previous studies suggest do not increase ARD risk.
• Primary outcome was ARD incidence, defined by diagnostic codes.

TAKEAWAY:

• There were no significant differences in incident ARDs between the three groups.
• Mean follow-up time was 0.88-1.53 years.
• The hazard ratio (HR) for developing ARDs with GLP-1-RAs exposure was 0.93 (95% CI, 0.66-1.30) compared with DPP-4 inhibitors.
• The HR for developing ARDs with SGLT2 inhibitor exposure was 0.97 (95% CI, 0.76-1.24).

IN PRACTICE: 

“Extended longitudinal data are needed to assess risk and benefit with longer-term exposure,” the authors wrote.

SOURCE: 

First author Derin Karacabeyli, MD, of the University of British Columbia, Vancouver, Canada, presented the study in abstract form at the Canadian Rheumatology Association (CRA) 2024 Annual Meeting in Winnipeg on February 29.

LIMITATIONS: 

The study was observational, which could have some residual or unmeasured confounding of data. The researchers relied on diagnostic codes and the average follow-up time was short. 

DISCLOSURES:

The study was funded by the Canadian Institutes of Health Research. The authors had no disclosures.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).

The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February. 

The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.

Wyost (120-mg/1.7-mL injection) is approved to:

• Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
• Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
• Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy

Jubbonti (60-mg/1-mL injection) is approved to:

• Treat postmenopausal women with osteoporosis who are at high risk for fracture
• Increase bone mass in men with osteoporosis who are at high risk for fracture
• Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
• Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.

Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.

Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).

The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February. 

The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.

Wyost (120-mg/1.7-mL injection) is approved to:

• Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
• Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
• Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy

Jubbonti (60-mg/1-mL injection) is approved to:

• Treat postmenopausal women with osteoporosis who are at high risk for fracture
• Increase bone mass in men with osteoporosis who are at high risk for fracture
• Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
• Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.

Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.

Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).

The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February. 

The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.

Wyost (120-mg/1.7-mL injection) is approved to:

• Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
• Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
• Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy

Jubbonti (60-mg/1-mL injection) is approved to:

• Treat postmenopausal women with osteoporosis who are at high risk for fracture
• Increase bone mass in men with osteoporosis who are at high risk for fracture
• Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
• Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.

Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.

Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”

A version of this article appeared on Medscape.com.

TOPLINE:

Researchers have identified six blood biomarkers tied to changes in arterial inflammation in patients with rheumatoid arthritis (RA).

METHODOLOGY:

• Researchers selected 24 candidate blood biomarkers previously associated with both RA and systemic inflammation.
• They measured biomarkers in 109 patients in the , which tested whether different treatments for RA reduced arterial inflammation.
• Along with biomarkers, they measured arterial inflammation via [18F] fluorodeoxyglucose (FDG)-PET/CT scans at baseline and 24 weeks.

TAKEAWAY:

• Baseline levels of the biomarkers serum amyloid A, C-reactive protein, soluble tumor necrosis factor receptor 1, adiponectin, YKL-4, and osteoprotegerin were associated with significant changes in arterial inflammation on FDG-PET/CT scans.
• Adding these biomarkers to predictive models improved the adjusted R2 from 0.20 to 0.32 (likelihood ratio test, P = .0005).
• Researchers plan to validate these associations in a larger, external patient cohort.

IN PRACTICE:

This study is too preliminary to have practical applications.

SOURCE:

The study, led by Daniel Solomon, MD, of Brigham and Women’s Hospital, Boston, was published on February 28 in the Journal of the American Heart Association.

DISCLOSURES:

The research was funded by a National Institutes of Health grant as well as the Foundation for the National Institutes of Health Biomarkers Consortium. Several authors reported salary support or consulting fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Researchers have identified six blood biomarkers tied to changes in arterial inflammation in patients with rheumatoid arthritis (RA).

METHODOLOGY:

• Researchers selected 24 candidate blood biomarkers previously associated with both RA and systemic inflammation.
• They measured biomarkers in 109 patients in the , which tested whether different treatments for RA reduced arterial inflammation.
• Along with biomarkers, they measured arterial inflammation via [18F] fluorodeoxyglucose (FDG)-PET/CT scans at baseline and 24 weeks.

TAKEAWAY:

• Baseline levels of the biomarkers serum amyloid A, C-reactive protein, soluble tumor necrosis factor receptor 1, adiponectin, YKL-4, and osteoprotegerin were associated with significant changes in arterial inflammation on FDG-PET/CT scans.
• Adding these biomarkers to predictive models improved the adjusted R2 from 0.20 to 0.32 (likelihood ratio test, P = .0005).
• Researchers plan to validate these associations in a larger, external patient cohort.

IN PRACTICE:

This study is too preliminary to have practical applications.

SOURCE:

The study, led by Daniel Solomon, MD, of Brigham and Women’s Hospital, Boston, was published on February 28 in the Journal of the American Heart Association.

DISCLOSURES:

The research was funded by a National Institutes of Health grant as well as the Foundation for the National Institutes of Health Biomarkers Consortium. Several authors reported salary support or consulting fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Researchers have identified six blood biomarkers tied to changes in arterial inflammation in patients with rheumatoid arthritis (RA).

METHODOLOGY:

• Researchers selected 24 candidate blood biomarkers previously associated with both RA and systemic inflammation.
• They measured biomarkers in 109 patients in the , which tested whether different treatments for RA reduced arterial inflammation.
• Along with biomarkers, they measured arterial inflammation via [18F] fluorodeoxyglucose (FDG)-PET/CT scans at baseline and 24 weeks.

TAKEAWAY:

• Baseline levels of the biomarkers serum amyloid A, C-reactive protein, soluble tumor necrosis factor receptor 1, adiponectin, YKL-4, and osteoprotegerin were associated with significant changes in arterial inflammation on FDG-PET/CT scans.
• Adding these biomarkers to predictive models improved the adjusted R2 from 0.20 to 0.32 (likelihood ratio test, P = .0005).
• Researchers plan to validate these associations in a larger, external patient cohort.

IN PRACTICE:

This study is too preliminary to have practical applications.

SOURCE:

The study, led by Daniel Solomon, MD, of Brigham and Women’s Hospital, Boston, was published on February 28 in the Journal of the American Heart Association.

DISCLOSURES:

The research was funded by a National Institutes of Health grant as well as the Foundation for the National Institutes of Health Biomarkers Consortium. Several authors reported salary support or consulting fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

People with gout are 58% more likely to develop cardiovascular disease (CVD), according to a new analysis. This increased risk was observed across 12 different cardiovascular conditions, including heart failure, arrhythmias, and valve diseases.

“These findings suggest that the organ damage associated with gout is likely to be much broader than originally thought,” Nathalie Conrad, PhD, senior author of the research and cardiovascular epidemiologist at KU Leuven, Leuven, Belgium, said in an email. This could be useful for future research on underlying biological mechanisms driving CVD risk in gout, she added.

While previous research has tied gout to increased cardiovascular risk, these studies “largely focused on coronary heart disease, stroke, and thromboembolic outcomes,” she explained, and have been smaller in size.

This new study included more than 862,000 individuals, which permitted researchers to investigate rarer CVD outcomes such as myocarditis and pericarditis.

For the study, researchers used electronic health records from the UK Clinical Practice Research Datalink, a primary care database that contains anonymized health data for about 22 million individuals. Using these data, they identified more than 152,600 individuals with gout. Patients included in the analysis were diagnosed between 2000 and 2017, younger than 80 years at diagnosis, and free of CVD for at least 12 months after their gout diagnosis.

Patients with gout were compared with nearly 710,000 controls, matched on demographic factors such as age, sex, and geographic region.

Researchers then investigated the incidence of 12 CVDs, including atherosclerotic diseases, degenerative and thromboembolic diseases, and arrythmias, between the two groups from January 1, 2000, to June 30, 2019.

The findings were published in the March 2024 issue of The Lancet Rheumatology. Overall, patients with gout were 58% more likely to develop any CVD than their matched comparators without gout. There was a higher disease incidence among patients with gout for each of the 12 conditions. This association was more pronounced in women (hazard ratio [HR], 1.88) than in men (HR, 1.49), and gout amplified the risk for CVD in younger individuals to a greater extent.

Individuals younger than 45 years with gout were more than twice as likely to develop CVD compared with similarly aged individuals without gout. For comparison, individuals aged 45-54 years with gout were 84% more likely to develop CVD, and individuals aged 55-64 years were 57% more likely to develop CVD than matched controls.

Conduction system disease had the highest incident risk (HR, 1.88), followed by heart failure and valve disease (HR, 1.85 for both).

Individuals with gout had higher rates of comorbidities than the controls, including hypertension, obesity, and dyslipidemia. Overall, CVD risk was slightly attenuated after adjustment for traditional CVD risk factors such as smoking, blood pressure, and body mass index but still significant: Patients with gout had a 31% higher risk for CVD than comparators.

This shows “that known CVD risk factors only explain part of the CVD risks seen in patients with gout,” Dr. Conrad said. Other factors such as inflammation and other disease activity factors could be at play, she explained, which would need to be explored in future research.

The study “shows the whole landscape” of CVD and gout, Michael H. Pillinger, MD, rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Grossman School of Medicine in New York City, said in an interview. He was not involved with the research.

“Every possible cardiovascular disease that they could think of was something that gout patients had more of than the non-gout patients,” he added. “I think this is going to be a paper that gets cited a lot, at minimum when describing the background of risk when we look at gout patients.”

The study had some limitations, including that researchers were unable to account for how medications such as nonsteroidal anti-inflammatory drugs, corticosteroids, colchicine, or allopurinol may have affected the association between gout and CVD.

“This is because analyses of nonrandomized treatment can be confounded by indication, wherein it is difficult to differentiate the effects of the treatment from underlying disease severity,” the authors wrote.

There was also a large amount of missing data on blood pressure, body mass index, smoking status, and other health information relevant to cardiovascular risk, so sensitivity analyses adjusting for these factors “should be interpreted with caution,” they added.

Dr. Pillinger also noted that the rates of comorbidities in the gout study population were lower than what have been found in US study populations. For example, about 40% of patients with gout in the analysis had hypertension, while other studies have suggested higher rates of 60%-70%, he said. However, it’s not clear if these differences could have affected outcomes. He added that these limitations do not “in any way weaken [the authors’] conclusion.”

The findings call for better strategies to reduce CVD risk in patients with gout, Dr. Conrad noted.

“Further improvements could come from better recognition and intervention on CVD risk factors (eg, through lifestyle changes or drug therapies where they are indicated), as well as proactive screening for heart disease in patients with gout, which could allow early diagnosis and interventions to delay more severe outcomes,” she added.

This study was funded by Research Foundation Flanders. Dr. Conrad was funded by a personal fellowship from the Research Foundation Flanders and a European Society of Cardiology research grant. She received royalties from Oxford University Innovation. Four of Dr. Conrad’s eight coauthors also reported financial relationships with pharmaceutical companies. Dr. Pillinger served as a consultant to Amgen, Federation Bio, Fortress Biotech, and Scilex, and he holds an investigator-initiated grant from Hikma.

A version of this article appeared on Medscape.com.

People with gout are 58% more likely to develop cardiovascular disease (CVD), according to a new analysis. This increased risk was observed across 12 different cardiovascular conditions, including heart failure, arrhythmias, and valve diseases.

“These findings suggest that the organ damage associated with gout is likely to be much broader than originally thought,” Nathalie Conrad, PhD, senior author of the research and cardiovascular epidemiologist at KU Leuven, Leuven, Belgium, said in an email. This could be useful for future research on underlying biological mechanisms driving CVD risk in gout, she added.

While previous research has tied gout to increased cardiovascular risk, these studies “largely focused on coronary heart disease, stroke, and thromboembolic outcomes,” she explained, and have been smaller in size.

This new study included more than 862,000 individuals, which permitted researchers to investigate rarer CVD outcomes such as myocarditis and pericarditis.

For the study, researchers used electronic health records from the UK Clinical Practice Research Datalink, a primary care database that contains anonymized health data for about 22 million individuals. Using these data, they identified more than 152,600 individuals with gout. Patients included in the analysis were diagnosed between 2000 and 2017, younger than 80 years at diagnosis, and free of CVD for at least 12 months after their gout diagnosis.

Patients with gout were compared with nearly 710,000 controls, matched on demographic factors such as age, sex, and geographic region.

Researchers then investigated the incidence of 12 CVDs, including atherosclerotic diseases, degenerative and thromboembolic diseases, and arrythmias, between the two groups from January 1, 2000, to June 30, 2019.

The findings were published in the March 2024 issue of The Lancet Rheumatology. Overall, patients with gout were 58% more likely to develop any CVD than their matched comparators without gout. There was a higher disease incidence among patients with gout for each of the 12 conditions. This association was more pronounced in women (hazard ratio [HR], 1.88) than in men (HR, 1.49), and gout amplified the risk for CVD in younger individuals to a greater extent.

Individuals younger than 45 years with gout were more than twice as likely to develop CVD compared with similarly aged individuals without gout. For comparison, individuals aged 45-54 years with gout were 84% more likely to develop CVD, and individuals aged 55-64 years were 57% more likely to develop CVD than matched controls.

Conduction system disease had the highest incident risk (HR, 1.88), followed by heart failure and valve disease (HR, 1.85 for both).

Individuals with gout had higher rates of comorbidities than the controls, including hypertension, obesity, and dyslipidemia. Overall, CVD risk was slightly attenuated after adjustment for traditional CVD risk factors such as smoking, blood pressure, and body mass index but still significant: Patients with gout had a 31% higher risk for CVD than comparators.

This shows “that known CVD risk factors only explain part of the CVD risks seen in patients with gout,” Dr. Conrad said. Other factors such as inflammation and other disease activity factors could be at play, she explained, which would need to be explored in future research.

The study “shows the whole landscape” of CVD and gout, Michael H. Pillinger, MD, rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Grossman School of Medicine in New York City, said in an interview. He was not involved with the research.

“Every possible cardiovascular disease that they could think of was something that gout patients had more of than the non-gout patients,” he added. “I think this is going to be a paper that gets cited a lot, at minimum when describing the background of risk when we look at gout patients.”

The study had some limitations, including that researchers were unable to account for how medications such as nonsteroidal anti-inflammatory drugs, corticosteroids, colchicine, or allopurinol may have affected the association between gout and CVD.

“This is because analyses of nonrandomized treatment can be confounded by indication, wherein it is difficult to differentiate the effects of the treatment from underlying disease severity,” the authors wrote.

There was also a large amount of missing data on blood pressure, body mass index, smoking status, and other health information relevant to cardiovascular risk, so sensitivity analyses adjusting for these factors “should be interpreted with caution,” they added.

Dr. Pillinger also noted that the rates of comorbidities in the gout study population were lower than what have been found in US study populations. For example, about 40% of patients with gout in the analysis had hypertension, while other studies have suggested higher rates of 60%-70%, he said. However, it’s not clear if these differences could have affected outcomes. He added that these limitations do not “in any way weaken [the authors’] conclusion.”

The findings call for better strategies to reduce CVD risk in patients with gout, Dr. Conrad noted.

“Further improvements could come from better recognition and intervention on CVD risk factors (eg, through lifestyle changes or drug therapies where they are indicated), as well as proactive screening for heart disease in patients with gout, which could allow early diagnosis and interventions to delay more severe outcomes,” she added.

This study was funded by Research Foundation Flanders. Dr. Conrad was funded by a personal fellowship from the Research Foundation Flanders and a European Society of Cardiology research grant. She received royalties from Oxford University Innovation. Four of Dr. Conrad’s eight coauthors also reported financial relationships with pharmaceutical companies. Dr. Pillinger served as a consultant to Amgen, Federation Bio, Fortress Biotech, and Scilex, and he holds an investigator-initiated grant from Hikma.

A version of this article appeared on Medscape.com.

People with gout are 58% more likely to develop cardiovascular disease (CVD), according to a new analysis. This increased risk was observed across 12 different cardiovascular conditions, including heart failure, arrhythmias, and valve diseases.

“These findings suggest that the organ damage associated with gout is likely to be much broader than originally thought,” Nathalie Conrad, PhD, senior author of the research and cardiovascular epidemiologist at KU Leuven, Leuven, Belgium, said in an email. This could be useful for future research on underlying biological mechanisms driving CVD risk in gout, she added.

While previous research has tied gout to increased cardiovascular risk, these studies “largely focused on coronary heart disease, stroke, and thromboembolic outcomes,” she explained, and have been smaller in size.

This new study included more than 862,000 individuals, which permitted researchers to investigate rarer CVD outcomes such as myocarditis and pericarditis.

For the study, researchers used electronic health records from the UK Clinical Practice Research Datalink, a primary care database that contains anonymized health data for about 22 million individuals. Using these data, they identified more than 152,600 individuals with gout. Patients included in the analysis were diagnosed between 2000 and 2017, younger than 80 years at diagnosis, and free of CVD for at least 12 months after their gout diagnosis.

Patients with gout were compared with nearly 710,000 controls, matched on demographic factors such as age, sex, and geographic region.

Researchers then investigated the incidence of 12 CVDs, including atherosclerotic diseases, degenerative and thromboembolic diseases, and arrythmias, between the two groups from January 1, 2000, to June 30, 2019.

The findings were published in the March 2024 issue of The Lancet Rheumatology. Overall, patients with gout were 58% more likely to develop any CVD than their matched comparators without gout. There was a higher disease incidence among patients with gout for each of the 12 conditions. This association was more pronounced in women (hazard ratio [HR], 1.88) than in men (HR, 1.49), and gout amplified the risk for CVD in younger individuals to a greater extent.

Individuals younger than 45 years with gout were more than twice as likely to develop CVD compared with similarly aged individuals without gout. For comparison, individuals aged 45-54 years with gout were 84% more likely to develop CVD, and individuals aged 55-64 years were 57% more likely to develop CVD than matched controls.

Conduction system disease had the highest incident risk (HR, 1.88), followed by heart failure and valve disease (HR, 1.85 for both).

Individuals with gout had higher rates of comorbidities than the controls, including hypertension, obesity, and dyslipidemia. Overall, CVD risk was slightly attenuated after adjustment for traditional CVD risk factors such as smoking, blood pressure, and body mass index but still significant: Patients with gout had a 31% higher risk for CVD than comparators.

This shows “that known CVD risk factors only explain part of the CVD risks seen in patients with gout,” Dr. Conrad said. Other factors such as inflammation and other disease activity factors could be at play, she explained, which would need to be explored in future research.

The study “shows the whole landscape” of CVD and gout, Michael H. Pillinger, MD, rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Grossman School of Medicine in New York City, said in an interview. He was not involved with the research.

“Every possible cardiovascular disease that they could think of was something that gout patients had more of than the non-gout patients,” he added. “I think this is going to be a paper that gets cited a lot, at minimum when describing the background of risk when we look at gout patients.”

The study had some limitations, including that researchers were unable to account for how medications such as nonsteroidal anti-inflammatory drugs, corticosteroids, colchicine, or allopurinol may have affected the association between gout and CVD.

“This is because analyses of nonrandomized treatment can be confounded by indication, wherein it is difficult to differentiate the effects of the treatment from underlying disease severity,” the authors wrote.

There was also a large amount of missing data on blood pressure, body mass index, smoking status, and other health information relevant to cardiovascular risk, so sensitivity analyses adjusting for these factors “should be interpreted with caution,” they added.

Dr. Pillinger also noted that the rates of comorbidities in the gout study population were lower than what have been found in US study populations. For example, about 40% of patients with gout in the analysis had hypertension, while other studies have suggested higher rates of 60%-70%, he said. However, it’s not clear if these differences could have affected outcomes. He added that these limitations do not “in any way weaken [the authors’] conclusion.”

The findings call for better strategies to reduce CVD risk in patients with gout, Dr. Conrad noted.

“Further improvements could come from better recognition and intervention on CVD risk factors (eg, through lifestyle changes or drug therapies where they are indicated), as well as proactive screening for heart disease in patients with gout, which could allow early diagnosis and interventions to delay more severe outcomes,” she added.

This study was funded by Research Foundation Flanders. Dr. Conrad was funded by a personal fellowship from the Research Foundation Flanders and a European Society of Cardiology research grant. She received royalties from Oxford University Innovation. Four of Dr. Conrad’s eight coauthors also reported financial relationships with pharmaceutical companies. Dr. Pillinger served as a consultant to Amgen, Federation Bio, Fortress Biotech, and Scilex, and he holds an investigator-initiated grant from Hikma.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

It’s no secret that regular exercise is important. But for patients with painful joints, it can be the last thing they want to do. Exercise is one of the cornerstones of managing arthritis, yet nearly one third of patients with arthritis are inactive.

Guidelines recommend that clinicians encourage their patients to engage in physical activity, but it can be difficult to know where to start.

This news organization recently spoke to experts on what resources are available, how much exercise is ideal, and how to motivate patients to move more.
 

What Are the Benefits of Exercise in Osteoarthritis?

Nearly all professional societies agree that exercise is one of the hallmarks of managing osteoarthritis (OA). According to two Cochrane reviews, there is high-equality evidence that exercise can help reduce pain as well as improve physical function in both hip and knee OA. In fact, physical activity can decrease pain and improve function by 40% in adults with arthritis, according to the Centers for Disease Control and Prevention.

Exercise also plays a large role in preventing disability by improving joint range of motion as well as maintaining muscle mass that supports joints.

There is also preliminary evidence that exercise could have a structural benefit to osteoarthritic joints. In a study of about 1200 individuals with knee OA, those who walked for exercise not only had reduced frequent knee pain, compared with non-walkers, but also were 20% less likely to have worsening of medial joint space narrowing.

Beyond symptom and impairment improvements, exercise can also play a role in staving off other chronic diseases linked to OA, such as cardiovascular disease and type 2 diabetes. Physical activity and exercise “are effective in preventing at least 35 chronic conditions and treating at least 26 chronic conditions, with one of the potential working mechanisms being exercise-induced anti-inflammatory effects,” wrote the authors of a commentary in the Journal of Orthopaedic & Sports Physical Therapy.

The known mental health benefits of exercise can also be beneficial for patients, as rates of depression and anxiety can be higher in people with arthritis than in the general population.
 

What Is the Ideal Amount of Exercise for Patients?

Current guidelines recommend that adults should get 150 minutes of moderate physical activity each week. But for patients with chronic pain, that may seem unachievable, Kelli Allen, PhD, professor of medicine and exercise physiologist at the University of North Carolina School of Medicine in Chapel Hill, said during a presentation at the American College of Rheumatology 2023 annual meeting in San Diego. Promisingly, research has shown that some exercise is better than none.

One study looking at over 1500 adults with lower extremity joint symptoms suggested that approximately 1 hour of physical activity per week increased the likelihood that participants remained disability-free over 4 years. In another analysis looking at 280 studies, researchers concluded that resistance training programs lasting 3-6 months resulted in moderate improvements in pain and physical function, but these benefits did not depend on exercise volume or participant adherence.

“These findings highlight the flexibility available for clinicians in the prescription of resistance exercise for knee and hip OA without compromising improvements in pain and physical function,” the authors wrote.

Step counts can be another way to measure activity, with 10,000 steps being a common target. But fewer steps a day can also yield health benefits. One study found that among nearly 1800 participants with knee OA, each additional 1000 steps per day was associated with a 16%-18% reduced risk of developing functional limitations 2 years later. Walking 6000 steps a day was the threshold that best determined who would develop functional limitations and who would not.

“I think it’s really a helpful message to encourage people with chronic pain that if you can get to 6000, maybe that’s a good goal,” Dr. Allen said.

Going for a 20-minute walk three times a week can be a good place to start, said Grace H. Lo, MD, associate professor in the Division of Immunology, Allergy, and Rheumatology at Baylor College of Medicine in Houston, Texas. For people who currently do not do any activity, Dr. Lo recommends starting small, like walking to get the mail every day. “Do something practical that is something they can sustain and keep in their daily activities that will help to increase their function and hopefully lessen some of their symptoms.”
 

Are Certain Types of Exercise More Beneficial?

There is no specific type of exercise that is best for OA, so it comes down to patient preference. The best exercise is “whatever somebody is actually going to do,” Dr. Allen noted.

Una Makris, MD, associate professor of internal medicine in the Division of Rheumatic Disease at the University of Texas Southwestern Medical Center and rheumatologist at the North Texas VA Health Care System in Dallas, Texas, said that her practice focuses on a combination of aerobic activity, functional balance, and strength training, as recommended by the World Health Organization.

“It’s not clear to me that one type of exercise is better than another; it’s more about what does this patient enjoy, and how can we make this a routine, so it is a sustainable behavior,” she told this news organization.

Generally, lower-impact exercises like biking, walking, or swimming tend to be better for OA, Dr. Lo added. Several studies have also shown tai chi to be beneficial in patients with OA, she said. More recently, Dr. Lo has conducted research on gardening as an exercise intervention for OA.

“It’s a great way to encourage people to exercise,” she said in an interview. “Besides the fact that they’re physically active, they can also be outside. There are a lot of mental health benefits to doing gardening as well.”

Dr. Allen added that certain exercises should be considered on the basis of an individual’s goals and physical needs. If someone has balance issues, for example, then yoga or tai chi could be useful to add to their exercise program, she said.
 

What Resources Are Available?

The Osteoarthritis Action Alliance has a list of 23 evidence-based exercise programs that have been shown to improve arthritis symptoms. These arthritis-appropriate, evidence-based interventions vary from instructor-led, in-person sessions to self-directed programs.

Walk with Ease (or Camine Con Gusto in Spanish) is one popular program, noted Dr. Allen. The program can be in-person or self-directed, with a required booklet that costs $11.95. However, there are discounted books for community-based organizations. The My Knee Exercise program, created by the University of Melbourne, Australia, provides a free, self-directed, 6-month strengthening program. The availability and cost of other programs are dependent on the format and location, the guide noted.

But understanding what programs are available in certain communities takes time, which can be a barrier to clinician referrals, noted Katie Huffman, director of education and outreach at OA Action Alliance.

“We would love to see these programs being covered by payers and health plans so that there’s incentive for providers to refer and patients to participate in the programs,” she noted.

While some states do cover a limited number of programs under Medicaid, coverage across states and payers is not yet universal.

In addition to these programs, the alliance has a simple guide to help plan workouts based on current activity level. The guide links to free exercises from CreakyJoints, an online community for people with arthritis, and the Arthritis Foundation.

Dr. Lo noted that the Veterans Affairs program, “VA Whole Health,” has free resources that are available to anyone. The provided videos offer tai chi, chair exercises, and guided meditations.

“It’s thoughtful to people who have some limitations in their physical activity,” she said.

Because the program is online, it could be difficult to access for those who are not comfortable with electronics, she said, “but if you can find a way to pass that, I think that this is an amazing resource,” she said.
 

How Do You Motivate Patients to Move?

“When it comes to motivation, I don’t think there is a one-size-fits-all approach,” said Dr. Makris. She tries to identify what matters most for each patient as a starting point. “When they can identify something in their day-to-day life that they value, then I like to link a physical activity-based goal to that,” she said. Setting physical activity goals using the mnemonic SMART (Specific, Measurable, Attainable, Realistic, and Timely) can be useful, she advised.

The OA Action Alliance also provides additional tools for clinicians on how to counsel patients on behavior change.

Understanding the patient’s lifestyle is also crucial when discussing physical activity, Dr. Lo added. “You have to give them practical solutions that they can actually incorporate into their lives,” she said.

Discussions around physical activity should be an ongoing part of clinic visits, both Dr. Lo and Dr. Makris agreed, to celebrate achievements and revise goals.

“I’m kind of notorious for being really slow in clinic because I just let people talk,” Dr. Lo said. “I do feel like these extra moments, when you spend time talking about these things, allow your recommendations to be more customized for the patients” and make the biggest impact.

Dr. Allen, Dr. Lo, and Dr. Makris reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

It’s no secret that regular exercise is important. But for patients with painful joints, it can be the last thing they want to do. Exercise is one of the cornerstones of managing arthritis, yet nearly one third of patients with arthritis are inactive.

Guidelines recommend that clinicians encourage their patients to engage in physical activity, but it can be difficult to know where to start.

This news organization recently spoke to experts on what resources are available, how much exercise is ideal, and how to motivate patients to move more.
 

What Are the Benefits of Exercise in Osteoarthritis?

Nearly all professional societies agree that exercise is one of the hallmarks of managing osteoarthritis (OA). According to two Cochrane reviews, there is high-equality evidence that exercise can help reduce pain as well as improve physical function in both hip and knee OA. In fact, physical activity can decrease pain and improve function by 40% in adults with arthritis, according to the Centers for Disease Control and Prevention.

Exercise also plays a large role in preventing disability by improving joint range of motion as well as maintaining muscle mass that supports joints.

There is also preliminary evidence that exercise could have a structural benefit to osteoarthritic joints. In a study of about 1200 individuals with knee OA, those who walked for exercise not only had reduced frequent knee pain, compared with non-walkers, but also were 20% less likely to have worsening of medial joint space narrowing.

Beyond symptom and impairment improvements, exercise can also play a role in staving off other chronic diseases linked to OA, such as cardiovascular disease and type 2 diabetes. Physical activity and exercise “are effective in preventing at least 35 chronic conditions and treating at least 26 chronic conditions, with one of the potential working mechanisms being exercise-induced anti-inflammatory effects,” wrote the authors of a commentary in the Journal of Orthopaedic & Sports Physical Therapy.

The known mental health benefits of exercise can also be beneficial for patients, as rates of depression and anxiety can be higher in people with arthritis than in the general population.
 

What Is the Ideal Amount of Exercise for Patients?

Current guidelines recommend that adults should get 150 minutes of moderate physical activity each week. But for patients with chronic pain, that may seem unachievable, Kelli Allen, PhD, professor of medicine and exercise physiologist at the University of North Carolina School of Medicine in Chapel Hill, said during a presentation at the American College of Rheumatology 2023 annual meeting in San Diego. Promisingly, research has shown that some exercise is better than none.

One study looking at over 1500 adults with lower extremity joint symptoms suggested that approximately 1 hour of physical activity per week increased the likelihood that participants remained disability-free over 4 years. In another analysis looking at 280 studies, researchers concluded that resistance training programs lasting 3-6 months resulted in moderate improvements in pain and physical function, but these benefits did not depend on exercise volume or participant adherence.

“These findings highlight the flexibility available for clinicians in the prescription of resistance exercise for knee and hip OA without compromising improvements in pain and physical function,” the authors wrote.

Step counts can be another way to measure activity, with 10,000 steps being a common target. But fewer steps a day can also yield health benefits. One study found that among nearly 1800 participants with knee OA, each additional 1000 steps per day was associated with a 16%-18% reduced risk of developing functional limitations 2 years later. Walking 6000 steps a day was the threshold that best determined who would develop functional limitations and who would not.

“I think it’s really a helpful message to encourage people with chronic pain that if you can get to 6000, maybe that’s a good goal,” Dr. Allen said.

Going for a 20-minute walk three times a week can be a good place to start, said Grace H. Lo, MD, associate professor in the Division of Immunology, Allergy, and Rheumatology at Baylor College of Medicine in Houston, Texas. For people who currently do not do any activity, Dr. Lo recommends starting small, like walking to get the mail every day. “Do something practical that is something they can sustain and keep in their daily activities that will help to increase their function and hopefully lessen some of their symptoms.”
 

Are Certain Types of Exercise More Beneficial?

There is no specific type of exercise that is best for OA, so it comes down to patient preference. The best exercise is “whatever somebody is actually going to do,” Dr. Allen noted.

Una Makris, MD, associate professor of internal medicine in the Division of Rheumatic Disease at the University of Texas Southwestern Medical Center and rheumatologist at the North Texas VA Health Care System in Dallas, Texas, said that her practice focuses on a combination of aerobic activity, functional balance, and strength training, as recommended by the World Health Organization.

“It’s not clear to me that one type of exercise is better than another; it’s more about what does this patient enjoy, and how can we make this a routine, so it is a sustainable behavior,” she told this news organization.

Generally, lower-impact exercises like biking, walking, or swimming tend to be better for OA, Dr. Lo added. Several studies have also shown tai chi to be beneficial in patients with OA, she said. More recently, Dr. Lo has conducted research on gardening as an exercise intervention for OA.

“It’s a great way to encourage people to exercise,” she said in an interview. “Besides the fact that they’re physically active, they can also be outside. There are a lot of mental health benefits to doing gardening as well.”

Dr. Allen added that certain exercises should be considered on the basis of an individual’s goals and physical needs. If someone has balance issues, for example, then yoga or tai chi could be useful to add to their exercise program, she said.
 

What Resources Are Available?

The Osteoarthritis Action Alliance has a list of 23 evidence-based exercise programs that have been shown to improve arthritis symptoms. These arthritis-appropriate, evidence-based interventions vary from instructor-led, in-person sessions to self-directed programs.

Walk with Ease (or Camine Con Gusto in Spanish) is one popular program, noted Dr. Allen. The program can be in-person or self-directed, with a required booklet that costs $11.95. However, there are discounted books for community-based organizations. The My Knee Exercise program, created by the University of Melbourne, Australia, provides a free, self-directed, 6-month strengthening program. The availability and cost of other programs are dependent on the format and location, the guide noted.

But understanding what programs are available in certain communities takes time, which can be a barrier to clinician referrals, noted Katie Huffman, director of education and outreach at OA Action Alliance.

“We would love to see these programs being covered by payers and health plans so that there’s incentive for providers to refer and patients to participate in the programs,” she noted.

While some states do cover a limited number of programs under Medicaid, coverage across states and payers is not yet universal.

In addition to these programs, the alliance has a simple guide to help plan workouts based on current activity level. The guide links to free exercises from CreakyJoints, an online community for people with arthritis, and the Arthritis Foundation.

Dr. Lo noted that the Veterans Affairs program, “VA Whole Health,” has free resources that are available to anyone. The provided videos offer tai chi, chair exercises, and guided meditations.

“It’s thoughtful to people who have some limitations in their physical activity,” she said.

Because the program is online, it could be difficult to access for those who are not comfortable with electronics, she said, “but if you can find a way to pass that, I think that this is an amazing resource,” she said.
 

How Do You Motivate Patients to Move?

“When it comes to motivation, I don’t think there is a one-size-fits-all approach,” said Dr. Makris. She tries to identify what matters most for each patient as a starting point. “When they can identify something in their day-to-day life that they value, then I like to link a physical activity-based goal to that,” she said. Setting physical activity goals using the mnemonic SMART (Specific, Measurable, Attainable, Realistic, and Timely) can be useful, she advised.

The OA Action Alliance also provides additional tools for clinicians on how to counsel patients on behavior change.

Understanding the patient’s lifestyle is also crucial when discussing physical activity, Dr. Lo added. “You have to give them practical solutions that they can actually incorporate into their lives,” she said.

Discussions around physical activity should be an ongoing part of clinic visits, both Dr. Lo and Dr. Makris agreed, to celebrate achievements and revise goals.

“I’m kind of notorious for being really slow in clinic because I just let people talk,” Dr. Lo said. “I do feel like these extra moments, when you spend time talking about these things, allow your recommendations to be more customized for the patients” and make the biggest impact.

Dr. Allen, Dr. Lo, and Dr. Makris reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

It’s no secret that regular exercise is important. But for patients with painful joints, it can be the last thing they want to do. Exercise is one of the cornerstones of managing arthritis, yet nearly one third of patients with arthritis are inactive.

Guidelines recommend that clinicians encourage their patients to engage in physical activity, but it can be difficult to know where to start.

This news organization recently spoke to experts on what resources are available, how much exercise is ideal, and how to motivate patients to move more.
 

What Are the Benefits of Exercise in Osteoarthritis?

Nearly all professional societies agree that exercise is one of the hallmarks of managing osteoarthritis (OA). According to two Cochrane reviews, there is high-equality evidence that exercise can help reduce pain as well as improve physical function in both hip and knee OA. In fact, physical activity can decrease pain and improve function by 40% in adults with arthritis, according to the Centers for Disease Control and Prevention.

Exercise also plays a large role in preventing disability by improving joint range of motion as well as maintaining muscle mass that supports joints.

There is also preliminary evidence that exercise could have a structural benefit to osteoarthritic joints. In a study of about 1200 individuals with knee OA, those who walked for exercise not only had reduced frequent knee pain, compared with non-walkers, but also were 20% less likely to have worsening of medial joint space narrowing.

Beyond symptom and impairment improvements, exercise can also play a role in staving off other chronic diseases linked to OA, such as cardiovascular disease and type 2 diabetes. Physical activity and exercise “are effective in preventing at least 35 chronic conditions and treating at least 26 chronic conditions, with one of the potential working mechanisms being exercise-induced anti-inflammatory effects,” wrote the authors of a commentary in the Journal of Orthopaedic & Sports Physical Therapy.

The known mental health benefits of exercise can also be beneficial for patients, as rates of depression and anxiety can be higher in people with arthritis than in the general population.
 

What Is the Ideal Amount of Exercise for Patients?

Current guidelines recommend that adults should get 150 minutes of moderate physical activity each week. But for patients with chronic pain, that may seem unachievable, Kelli Allen, PhD, professor of medicine and exercise physiologist at the University of North Carolina School of Medicine in Chapel Hill, said during a presentation at the American College of Rheumatology 2023 annual meeting in San Diego. Promisingly, research has shown that some exercise is better than none.

One study looking at over 1500 adults with lower extremity joint symptoms suggested that approximately 1 hour of physical activity per week increased the likelihood that participants remained disability-free over 4 years. In another analysis looking at 280 studies, researchers concluded that resistance training programs lasting 3-6 months resulted in moderate improvements in pain and physical function, but these benefits did not depend on exercise volume or participant adherence.

“These findings highlight the flexibility available for clinicians in the prescription of resistance exercise for knee and hip OA without compromising improvements in pain and physical function,” the authors wrote.

Step counts can be another way to measure activity, with 10,000 steps being a common target. But fewer steps a day can also yield health benefits. One study found that among nearly 1800 participants with knee OA, each additional 1000 steps per day was associated with a 16%-18% reduced risk of developing functional limitations 2 years later. Walking 6000 steps a day was the threshold that best determined who would develop functional limitations and who would not.

“I think it’s really a helpful message to encourage people with chronic pain that if you can get to 6000, maybe that’s a good goal,” Dr. Allen said.

Going for a 20-minute walk three times a week can be a good place to start, said Grace H. Lo, MD, associate professor in the Division of Immunology, Allergy, and Rheumatology at Baylor College of Medicine in Houston, Texas. For people who currently do not do any activity, Dr. Lo recommends starting small, like walking to get the mail every day. “Do something practical that is something they can sustain and keep in their daily activities that will help to increase their function and hopefully lessen some of their symptoms.”
 

Are Certain Types of Exercise More Beneficial?

There is no specific type of exercise that is best for OA, so it comes down to patient preference. The best exercise is “whatever somebody is actually going to do,” Dr. Allen noted.

Una Makris, MD, associate professor of internal medicine in the Division of Rheumatic Disease at the University of Texas Southwestern Medical Center and rheumatologist at the North Texas VA Health Care System in Dallas, Texas, said that her practice focuses on a combination of aerobic activity, functional balance, and strength training, as recommended by the World Health Organization.

“It’s not clear to me that one type of exercise is better than another; it’s more about what does this patient enjoy, and how can we make this a routine, so it is a sustainable behavior,” she told this news organization.

Generally, lower-impact exercises like biking, walking, or swimming tend to be better for OA, Dr. Lo added. Several studies have also shown tai chi to be beneficial in patients with OA, she said. More recently, Dr. Lo has conducted research on gardening as an exercise intervention for OA.

“It’s a great way to encourage people to exercise,” she said in an interview. “Besides the fact that they’re physically active, they can also be outside. There are a lot of mental health benefits to doing gardening as well.”

Dr. Allen added that certain exercises should be considered on the basis of an individual’s goals and physical needs. If someone has balance issues, for example, then yoga or tai chi could be useful to add to their exercise program, she said.
 

What Resources Are Available?

The Osteoarthritis Action Alliance has a list of 23 evidence-based exercise programs that have been shown to improve arthritis symptoms. These arthritis-appropriate, evidence-based interventions vary from instructor-led, in-person sessions to self-directed programs.

Walk with Ease (or Camine Con Gusto in Spanish) is one popular program, noted Dr. Allen. The program can be in-person or self-directed, with a required booklet that costs $11.95. However, there are discounted books for community-based organizations. The My Knee Exercise program, created by the University of Melbourne, Australia, provides a free, self-directed, 6-month strengthening program. The availability and cost of other programs are dependent on the format and location, the guide noted.

But understanding what programs are available in certain communities takes time, which can be a barrier to clinician referrals, noted Katie Huffman, director of education and outreach at OA Action Alliance.

“We would love to see these programs being covered by payers and health plans so that there’s incentive for providers to refer and patients to participate in the programs,” she noted.

While some states do cover a limited number of programs under Medicaid, coverage across states and payers is not yet universal.

In addition to these programs, the alliance has a simple guide to help plan workouts based on current activity level. The guide links to free exercises from CreakyJoints, an online community for people with arthritis, and the Arthritis Foundation.

Dr. Lo noted that the Veterans Affairs program, “VA Whole Health,” has free resources that are available to anyone. The provided videos offer tai chi, chair exercises, and guided meditations.

“It’s thoughtful to people who have some limitations in their physical activity,” she said.

Because the program is online, it could be difficult to access for those who are not comfortable with electronics, she said, “but if you can find a way to pass that, I think that this is an amazing resource,” she said.
 

How Do You Motivate Patients to Move?

“When it comes to motivation, I don’t think there is a one-size-fits-all approach,” said Dr. Makris. She tries to identify what matters most for each patient as a starting point. “When they can identify something in their day-to-day life that they value, then I like to link a physical activity-based goal to that,” she said. Setting physical activity goals using the mnemonic SMART (Specific, Measurable, Attainable, Realistic, and Timely) can be useful, she advised.

The OA Action Alliance also provides additional tools for clinicians on how to counsel patients on behavior change.

Understanding the patient’s lifestyle is also crucial when discussing physical activity, Dr. Lo added. “You have to give them practical solutions that they can actually incorporate into their lives,” she said.

Discussions around physical activity should be an ongoing part of clinic visits, both Dr. Lo and Dr. Makris agreed, to celebrate achievements and revise goals.

“I’m kind of notorious for being really slow in clinic because I just let people talk,” Dr. Lo said. “I do feel like these extra moments, when you spend time talking about these things, allow your recommendations to be more customized for the patients” and make the biggest impact.

Dr. Allen, Dr. Lo, and Dr. Makris reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).

In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.

The study was published online on February 1 in eClinicalMedicine.

While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
 

Pregnancy Outcome Risks Varied Between IMIDs

To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.

Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.

In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.

After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.

But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.

“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.

Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.

Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.

“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
 

A Large Study, But How Representative Is It?

Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”

She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.

“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.

“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”

Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.

The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.

However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.

“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.

Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.

“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.

The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.

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

Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).

In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.

The study was published online on February 1 in eClinicalMedicine.

While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
 

Pregnancy Outcome Risks Varied Between IMIDs

To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.

Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.

In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.

After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.

But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.

“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.

Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.

Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.

“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
 

A Large Study, But How Representative Is It?

Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”

She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.

“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.

“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”

Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.

The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.

However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.

“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.

Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.

“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.

The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.

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

Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).

In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.

The study was published online on February 1 in eClinicalMedicine.

While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
 

Pregnancy Outcome Risks Varied Between IMIDs

To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.

Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.

In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.

After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.

But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.

“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.

Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.

Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.

“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
 

A Large Study, But How Representative Is It?

Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”

She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.

“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.

“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”

Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.

The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.

However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.

“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.

Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.

“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.

The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.

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

Patients with calcium pyrophosphate deposition (CPPD) disease, also known as pseudogout, have an 80% higher risk for fracture than individuals who do not have the disease, according to a new analysis.

This trend was driven by wrist fractures, where there was a more than threefold increased risk.

Previous studies identified an association between CPPD and low bone mineral density, and there is growing evidence suggesting that the dysregulation of osteoprotegerin — a molecule that is important in the regulation of osteoclasts — may be associated with early-onset CPPD, noted Sara K. Tedeschi, MD, MPH, the lead author of the study and head of crystal-induced arthritic diseases at Brigham and Women’s Hospital, Boston, Massachusetts.

However, CPPD’s association with fracture risk has yet to be explored.

In the study, Dr. Tedeschi and colleagues used Mass General Brigham electronic health record (EHR) data from 1991 to 2023 to identify 1148 individuals with acute calcium pyrophosphate (CPP) crystal arthritis. The index date was defined as the first documentation of pseudogout or synovial fluid CPP crystals. These patients were matched to 3730 comparators based on healthcare encounters within 30 days of the index date of a patient with CPPD. Patients were also matched based on the year of their first EHR encounter. Patients with a fracture documented prior to the index date were excluded from the analysis.

The primary outcome was the first fracture of the humerus, knee, wrist, hip, or pelvis, detected via published algorithms using diagnostic and procedural codes.

The research was published on January 14 in Arthritis & Rheumatology.

Although participants were not matched on age or sex, the average age was 73, and most participants were female. In total, 83.1% of participants in the CPPD group and 80.0% of those in the control group were White.

After adjustment for confounding factors including age, sex, comorbidities, and glucocorticoid use, CPPD was associated with an 80% higher risk for any fracture (hazard risk [HR], 1.8). Fracture risk was highest for the wrist (HR, 3.6).

Patients with CPPD had a 40% higher risk to experience a humerus or pelvis fracture and a 30% higher risk for hip fractures, but the results were not statistically significant.

The results were similar for sensitivity analyses that excluded patients who were prescribed glucocorticoids, treatment for osteoporosis, or had a diagnosis of rheumatoid arthritis.

Asked to comment, John D. FitzGerald, MD, PhD, clinical chief of rheumatology at the University of California, Los Angeles, noted that these associations were “convincing and strong. I thought it was a very good study and important work. CPPD is common and osteoporosis is common, so better understanding the connection is important.”

It’s still not clear why the risk for wrist fractures was highest, but Dr. Tedeschi had two hypotheses. The researchers were unable to assess for falls in this dataset, but it’s possible that patients with CPPD experiencing joint pain could fall and try to brace themselves with an outstretched arm, leading to a wrist fracture.

CPPD also commonly affects the wrist, “so it’s possible that if CPPD is affecting the wrist and if there is an association between CPPD and low bone density, maybe there’s particularly low bone density at the wrist,” she said.

Dr. FitzGerald agreed that both hypotheses were plausible, but “with the retrospective study, there could be a lot of things that are unobserved or unexplained,” he added.

Dr. Tedeschi is interested in exploring what could be causing the association with an increased fracture risk in future research.

“I hope this draws attention to the fact that people with CPPD can have related medical problems that are outside of their joints,” added Dr. Tedeschi. “Thinking about routine screening for osteopenia and osteoporosis could be a good first step in patients with CPPD.”

The study was funded by grants from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Tedeschi has worked as a consultant for Novartis. Dr. FitzGerald reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with calcium pyrophosphate deposition (CPPD) disease, also known as pseudogout, have an 80% higher risk for fracture than individuals who do not have the disease, according to a new analysis.

This trend was driven by wrist fractures, where there was a more than threefold increased risk.

Previous studies identified an association between CPPD and low bone mineral density, and there is growing evidence suggesting that the dysregulation of osteoprotegerin — a molecule that is important in the regulation of osteoclasts — may be associated with early-onset CPPD, noted Sara K. Tedeschi, MD, MPH, the lead author of the study and head of crystal-induced arthritic diseases at Brigham and Women’s Hospital, Boston, Massachusetts.

However, CPPD’s association with fracture risk has yet to be explored.

In the study, Dr. Tedeschi and colleagues used Mass General Brigham electronic health record (EHR) data from 1991 to 2023 to identify 1148 individuals with acute calcium pyrophosphate (CPP) crystal arthritis. The index date was defined as the first documentation of pseudogout or synovial fluid CPP crystals. These patients were matched to 3730 comparators based on healthcare encounters within 30 days of the index date of a patient with CPPD. Patients were also matched based on the year of their first EHR encounter. Patients with a fracture documented prior to the index date were excluded from the analysis.

The primary outcome was the first fracture of the humerus, knee, wrist, hip, or pelvis, detected via published algorithms using diagnostic and procedural codes.

The research was published on January 14 in Arthritis & Rheumatology.

Although participants were not matched on age or sex, the average age was 73, and most participants were female. In total, 83.1% of participants in the CPPD group and 80.0% of those in the control group were White.

After adjustment for confounding factors including age, sex, comorbidities, and glucocorticoid use, CPPD was associated with an 80% higher risk for any fracture (hazard risk [HR], 1.8). Fracture risk was highest for the wrist (HR, 3.6).

Patients with CPPD had a 40% higher risk to experience a humerus or pelvis fracture and a 30% higher risk for hip fractures, but the results were not statistically significant.

The results were similar for sensitivity analyses that excluded patients who were prescribed glucocorticoids, treatment for osteoporosis, or had a diagnosis of rheumatoid arthritis.

Asked to comment, John D. FitzGerald, MD, PhD, clinical chief of rheumatology at the University of California, Los Angeles, noted that these associations were “convincing and strong. I thought it was a very good study and important work. CPPD is common and osteoporosis is common, so better understanding the connection is important.”

It’s still not clear why the risk for wrist fractures was highest, but Dr. Tedeschi had two hypotheses. The researchers were unable to assess for falls in this dataset, but it’s possible that patients with CPPD experiencing joint pain could fall and try to brace themselves with an outstretched arm, leading to a wrist fracture.

CPPD also commonly affects the wrist, “so it’s possible that if CPPD is affecting the wrist and if there is an association between CPPD and low bone density, maybe there’s particularly low bone density at the wrist,” she said.

Dr. FitzGerald agreed that both hypotheses were plausible, but “with the retrospective study, there could be a lot of things that are unobserved or unexplained,” he added.

Dr. Tedeschi is interested in exploring what could be causing the association with an increased fracture risk in future research.

“I hope this draws attention to the fact that people with CPPD can have related medical problems that are outside of their joints,” added Dr. Tedeschi. “Thinking about routine screening for osteopenia and osteoporosis could be a good first step in patients with CPPD.”

The study was funded by grants from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Tedeschi has worked as a consultant for Novartis. Dr. FitzGerald reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with calcium pyrophosphate deposition (CPPD) disease, also known as pseudogout, have an 80% higher risk for fracture than individuals who do not have the disease, according to a new analysis.

This trend was driven by wrist fractures, where there was a more than threefold increased risk.

Previous studies identified an association between CPPD and low bone mineral density, and there is growing evidence suggesting that the dysregulation of osteoprotegerin — a molecule that is important in the regulation of osteoclasts — may be associated with early-onset CPPD, noted Sara K. Tedeschi, MD, MPH, the lead author of the study and head of crystal-induced arthritic diseases at Brigham and Women’s Hospital, Boston, Massachusetts.

However, CPPD’s association with fracture risk has yet to be explored.

In the study, Dr. Tedeschi and colleagues used Mass General Brigham electronic health record (EHR) data from 1991 to 2023 to identify 1148 individuals with acute calcium pyrophosphate (CPP) crystal arthritis. The index date was defined as the first documentation of pseudogout or synovial fluid CPP crystals. These patients were matched to 3730 comparators based on healthcare encounters within 30 days of the index date of a patient with CPPD. Patients were also matched based on the year of their first EHR encounter. Patients with a fracture documented prior to the index date were excluded from the analysis.

The primary outcome was the first fracture of the humerus, knee, wrist, hip, or pelvis, detected via published algorithms using diagnostic and procedural codes.

The research was published on January 14 in Arthritis & Rheumatology.

Although participants were not matched on age or sex, the average age was 73, and most participants were female. In total, 83.1% of participants in the CPPD group and 80.0% of those in the control group were White.

After adjustment for confounding factors including age, sex, comorbidities, and glucocorticoid use, CPPD was associated with an 80% higher risk for any fracture (hazard risk [HR], 1.8). Fracture risk was highest for the wrist (HR, 3.6).

Patients with CPPD had a 40% higher risk to experience a humerus or pelvis fracture and a 30% higher risk for hip fractures, but the results were not statistically significant.

The results were similar for sensitivity analyses that excluded patients who were prescribed glucocorticoids, treatment for osteoporosis, or had a diagnosis of rheumatoid arthritis.

Asked to comment, John D. FitzGerald, MD, PhD, clinical chief of rheumatology at the University of California, Los Angeles, noted that these associations were “convincing and strong. I thought it was a very good study and important work. CPPD is common and osteoporosis is common, so better understanding the connection is important.”

It’s still not clear why the risk for wrist fractures was highest, but Dr. Tedeschi had two hypotheses. The researchers were unable to assess for falls in this dataset, but it’s possible that patients with CPPD experiencing joint pain could fall and try to brace themselves with an outstretched arm, leading to a wrist fracture.

CPPD also commonly affects the wrist, “so it’s possible that if CPPD is affecting the wrist and if there is an association between CPPD and low bone density, maybe there’s particularly low bone density at the wrist,” she said.

Dr. FitzGerald agreed that both hypotheses were plausible, but “with the retrospective study, there could be a lot of things that are unobserved or unexplained,” he added.

Dr. Tedeschi is interested in exploring what could be causing the association with an increased fracture risk in future research.

“I hope this draws attention to the fact that people with CPPD can have related medical problems that are outside of their joints,” added Dr. Tedeschi. “Thinking about routine screening for osteopenia and osteoporosis could be a good first step in patients with CPPD.”

The study was funded by grants from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Tedeschi has worked as a consultant for Novartis. Dr. FitzGerald reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Sirolimus may be an effective treatment for patients with persistent cutaneous sarcoidosis.

In a small clinical trial, 7 of 10 patients treated with sirolimus via oral solution had improvements in skin lesions after 4 months, which was sustained for up to 2 years after the study concluded.

The results suggested that mechanistic target of rapamycin (mTOR) inhibition is a potential therapeutic avenue for sarcoidosis, which the authors said should be explored in larger clinical trials. 

In the past decade, there has been a growing amount of evidence suggesting mTOR’s role in sarcoidosis. In 2017, researchers showed that activation of mTOR in macrophages could cause progressive sarcoidosis in mice. In additional studies, high levels of mTOR activity were detected in human sarcoidosis granulomas in various organs, including the skin, lung, and heart.

Three case reports also documented using the mTOR inhibitor sirolimus to effectively treat systemic sarcoidosis.

“Although all reports observed improvement of the disease following the treatment, no clinical trial investigating the efficacy and safety of sirolimus in patients with sarcoidosis had been published” prior to this study, wrote senior author Georg Stary, MD, of the Medical University of Vienna and the Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria, and colleagues. 

The findings were published in the The Lancet Rheumatology.

For the study, researchers recruited 16 individuals with persistent and glucocorticoid-refractory cutaneous sarcoidosis between September 2019 and June 2021. A total of 14 participants were randomly assigned to the topical phase of the study, whereas two immediately received systemic treatment. All treatment was conducted at Vienna General Hospital.

In the placebo-controlled, double-blinded topical treatment arm, patients received either 0.1% topical sirolimus in Vaseline or Vaseline alone (placebo) twice daily for 2 months. After a 1-month washout period, participants were switched to the alternate treatment arm for an additional 2 months.

Following this topical phase and an additional 1-month washout period, all remaining participants received systemic sirolimus via a 1-mg/mL solution, starting with a 6-mg loading dose and continuing with 2 mg once daily for 4 months. The primary outcome was change in Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) from baseline, with decrease of more than five points representing a response to treatment.

A total of 10 patients completed the trial.

There was no change in CSAMI in either topical treatment groups. In the systemic group, 70% of patients had clinical improvement in skin lesions, with three responders in this group having complete resolution of skin lesions. The median change in CSAMI was −7.0 points (P = .018). 

This improvement persisted for 2 months following study conclusion, with more pronounced improvement from baseline after 2 years of drug-free follow-up (−11.5 points).

There were no serious adverse events reported during the study, but 42% of patients treated with systemic sirolimus reported mild skin reactions, such as acne and eczema. Other related adverse events were hypertriglyceridemia (17%), hyperglycemia (17%), and proteinuria (8%).

Compared with clinical outcomes with tofacitinib and tumor necrosis factor (TNF) inhibitors, “the strength of our study lies in the sustained treatment effect after drug withdrawal among all responders. This prolonged effect has not yet been explored with tofacitinib, whereas with TNF inhibitors disease relapse was seen in more than 50% of patients at 3-8 months,” the authors wrote.

The researchers also analyzed participants’ skin biopsies to gain a better understanding of how mTOR inhibition affected granuloma structures. They found that, at baseline, mTOR activity was significantly lower in the fibroblasts of treatment nonresponders than in responders. They speculated that lower expression of mTOR could make these granuloma-associated cells resistant to systemic sirolimus.

These promising findings combine “clinical response with a molecular analysis,” Avrom Caplan, MD, co-director of the Sarcoidosis Program at NYU Langone in New York City, told this news organization. He was not involved with the research. Adding molecular information to clinical outcome data “helps solidify that [the mTOR] pathway has relevance in the sarcoid granuloma formation.”

The study had a limited sample size — a challenge for many clinical trials of rare diseases, Dr. Caplan said. Larger clinical trials are necessary to explore mTOR inhibition in sarcoidosis, both he and the authors agreed. A larger trial could also include greater heterogeneity of patients, including varied sarcoid presentation and demographics, Dr. Caplan noted. In this study, all but one participants were White individuals, and 63% of participants were female.

Larger studies could also address important questions on ideal length of therapy, dosing, and where this therapy “would fall within the therapeutic step ladder,” Dr. Caplan continued. 

Whether mTOR inhibition could be effective at treating individuals with sarcoidosis in other organs beyond the skin is also unknown. 

“If the pathogenesis of sarcoid granuloma formation does include mTOR upregulation, which they are showing here…then you could hypothesize that, yes, using this therapy could benefit other organs,” he said. “But that has to be investigated in larger trials.”

The study was funded in part by a Vienna Science and Technology Fund project. Several authors report receiving grants from the Austrian Science Fund and one from the Ann Theodore Foundation Breakthrough Sarcoidosis Initiative. Dr. Caplan reported no relevant financial relationships.

A version of this article appeared on Medscape.com .

Sirolimus may be an effective treatment for patients with persistent cutaneous sarcoidosis.

In a small clinical trial, 7 of 10 patients treated with sirolimus via oral solution had improvements in skin lesions after 4 months, which was sustained for up to 2 years after the study concluded.

The results suggested that mechanistic target of rapamycin (mTOR) inhibition is a potential therapeutic avenue for sarcoidosis, which the authors said should be explored in larger clinical trials. 

In the past decade, there has been a growing amount of evidence suggesting mTOR’s role in sarcoidosis. In 2017, researchers showed that activation of mTOR in macrophages could cause progressive sarcoidosis in mice. In additional studies, high levels of mTOR activity were detected in human sarcoidosis granulomas in various organs, including the skin, lung, and heart.

Three case reports also documented using the mTOR inhibitor sirolimus to effectively treat systemic sarcoidosis.

“Although all reports observed improvement of the disease following the treatment, no clinical trial investigating the efficacy and safety of sirolimus in patients with sarcoidosis had been published” prior to this study, wrote senior author Georg Stary, MD, of the Medical University of Vienna and the Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria, and colleagues. 

The findings were published in the The Lancet Rheumatology.

For the study, researchers recruited 16 individuals with persistent and glucocorticoid-refractory cutaneous sarcoidosis between September 2019 and June 2021. A total of 14 participants were randomly assigned to the topical phase of the study, whereas two immediately received systemic treatment. All treatment was conducted at Vienna General Hospital.

In the placebo-controlled, double-blinded topical treatment arm, patients received either 0.1% topical sirolimus in Vaseline or Vaseline alone (placebo) twice daily for 2 months. After a 1-month washout period, participants were switched to the alternate treatment arm for an additional 2 months.

Following this topical phase and an additional 1-month washout period, all remaining participants received systemic sirolimus via a 1-mg/mL solution, starting with a 6-mg loading dose and continuing with 2 mg once daily for 4 months. The primary outcome was change in Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) from baseline, with decrease of more than five points representing a response to treatment.

A total of 10 patients completed the trial.

There was no change in CSAMI in either topical treatment groups. In the systemic group, 70% of patients had clinical improvement in skin lesions, with three responders in this group having complete resolution of skin lesions. The median change in CSAMI was −7.0 points (P = .018). 

This improvement persisted for 2 months following study conclusion, with more pronounced improvement from baseline after 2 years of drug-free follow-up (−11.5 points).

There were no serious adverse events reported during the study, but 42% of patients treated with systemic sirolimus reported mild skin reactions, such as acne and eczema. Other related adverse events were hypertriglyceridemia (17%), hyperglycemia (17%), and proteinuria (8%).

Compared with clinical outcomes with tofacitinib and tumor necrosis factor (TNF) inhibitors, “the strength of our study lies in the sustained treatment effect after drug withdrawal among all responders. This prolonged effect has not yet been explored with tofacitinib, whereas with TNF inhibitors disease relapse was seen in more than 50% of patients at 3-8 months,” the authors wrote.

The researchers also analyzed participants’ skin biopsies to gain a better understanding of how mTOR inhibition affected granuloma structures. They found that, at baseline, mTOR activity was significantly lower in the fibroblasts of treatment nonresponders than in responders. They speculated that lower expression of mTOR could make these granuloma-associated cells resistant to systemic sirolimus.

These promising findings combine “clinical response with a molecular analysis,” Avrom Caplan, MD, co-director of the Sarcoidosis Program at NYU Langone in New York City, told this news organization. He was not involved with the research. Adding molecular information to clinical outcome data “helps solidify that [the mTOR] pathway has relevance in the sarcoid granuloma formation.”

The study had a limited sample size — a challenge for many clinical trials of rare diseases, Dr. Caplan said. Larger clinical trials are necessary to explore mTOR inhibition in sarcoidosis, both he and the authors agreed. A larger trial could also include greater heterogeneity of patients, including varied sarcoid presentation and demographics, Dr. Caplan noted. In this study, all but one participants were White individuals, and 63% of participants were female.

Larger studies could also address important questions on ideal length of therapy, dosing, and where this therapy “would fall within the therapeutic step ladder,” Dr. Caplan continued. 

Whether mTOR inhibition could be effective at treating individuals with sarcoidosis in other organs beyond the skin is also unknown. 

“If the pathogenesis of sarcoid granuloma formation does include mTOR upregulation, which they are showing here…then you could hypothesize that, yes, using this therapy could benefit other organs,” he said. “But that has to be investigated in larger trials.”

The study was funded in part by a Vienna Science and Technology Fund project. Several authors report receiving grants from the Austrian Science Fund and one from the Ann Theodore Foundation Breakthrough Sarcoidosis Initiative. Dr. Caplan reported no relevant financial relationships.

A version of this article appeared on Medscape.com .

Sirolimus may be an effective treatment for patients with persistent cutaneous sarcoidosis.

In a small clinical trial, 7 of 10 patients treated with sirolimus via oral solution had improvements in skin lesions after 4 months, which was sustained for up to 2 years after the study concluded.

The results suggested that mechanistic target of rapamycin (mTOR) inhibition is a potential therapeutic avenue for sarcoidosis, which the authors said should be explored in larger clinical trials. 

In the past decade, there has been a growing amount of evidence suggesting mTOR’s role in sarcoidosis. In 2017, researchers showed that activation of mTOR in macrophages could cause progressive sarcoidosis in mice. In additional studies, high levels of mTOR activity were detected in human sarcoidosis granulomas in various organs, including the skin, lung, and heart.

Three case reports also documented using the mTOR inhibitor sirolimus to effectively treat systemic sarcoidosis.

“Although all reports observed improvement of the disease following the treatment, no clinical trial investigating the efficacy and safety of sirolimus in patients with sarcoidosis had been published” prior to this study, wrote senior author Georg Stary, MD, of the Medical University of Vienna and the Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria, and colleagues. 

The findings were published in the The Lancet Rheumatology.

For the study, researchers recruited 16 individuals with persistent and glucocorticoid-refractory cutaneous sarcoidosis between September 2019 and June 2021. A total of 14 participants were randomly assigned to the topical phase of the study, whereas two immediately received systemic treatment. All treatment was conducted at Vienna General Hospital.

In the placebo-controlled, double-blinded topical treatment arm, patients received either 0.1% topical sirolimus in Vaseline or Vaseline alone (placebo) twice daily for 2 months. After a 1-month washout period, participants were switched to the alternate treatment arm for an additional 2 months.

Following this topical phase and an additional 1-month washout period, all remaining participants received systemic sirolimus via a 1-mg/mL solution, starting with a 6-mg loading dose and continuing with 2 mg once daily for 4 months. The primary outcome was change in Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) from baseline, with decrease of more than five points representing a response to treatment.

A total of 10 patients completed the trial.

There was no change in CSAMI in either topical treatment groups. In the systemic group, 70% of patients had clinical improvement in skin lesions, with three responders in this group having complete resolution of skin lesions. The median change in CSAMI was −7.0 points (P = .018). 

This improvement persisted for 2 months following study conclusion, with more pronounced improvement from baseline after 2 years of drug-free follow-up (−11.5 points).

There were no serious adverse events reported during the study, but 42% of patients treated with systemic sirolimus reported mild skin reactions, such as acne and eczema. Other related adverse events were hypertriglyceridemia (17%), hyperglycemia (17%), and proteinuria (8%).

Compared with clinical outcomes with tofacitinib and tumor necrosis factor (TNF) inhibitors, “the strength of our study lies in the sustained treatment effect after drug withdrawal among all responders. This prolonged effect has not yet been explored with tofacitinib, whereas with TNF inhibitors disease relapse was seen in more than 50% of patients at 3-8 months,” the authors wrote.

The researchers also analyzed participants’ skin biopsies to gain a better understanding of how mTOR inhibition affected granuloma structures. They found that, at baseline, mTOR activity was significantly lower in the fibroblasts of treatment nonresponders than in responders. They speculated that lower expression of mTOR could make these granuloma-associated cells resistant to systemic sirolimus.

These promising findings combine “clinical response with a molecular analysis,” Avrom Caplan, MD, co-director of the Sarcoidosis Program at NYU Langone in New York City, told this news organization. He was not involved with the research. Adding molecular information to clinical outcome data “helps solidify that [the mTOR] pathway has relevance in the sarcoid granuloma formation.”

The study had a limited sample size — a challenge for many clinical trials of rare diseases, Dr. Caplan said. Larger clinical trials are necessary to explore mTOR inhibition in sarcoidosis, both he and the authors agreed. A larger trial could also include greater heterogeneity of patients, including varied sarcoid presentation and demographics, Dr. Caplan noted. In this study, all but one participants were White individuals, and 63% of participants were female.

Larger studies could also address important questions on ideal length of therapy, dosing, and where this therapy “would fall within the therapeutic step ladder,” Dr. Caplan continued. 

Whether mTOR inhibition could be effective at treating individuals with sarcoidosis in other organs beyond the skin is also unknown. 

“If the pathogenesis of sarcoid granuloma formation does include mTOR upregulation, which they are showing here…then you could hypothesize that, yes, using this therapy could benefit other organs,” he said. “But that has to be investigated in larger trials.”

The study was funded in part by a Vienna Science and Technology Fund project. Several authors report receiving grants from the Austrian Science Fund and one from the Ann Theodore Foundation Breakthrough Sarcoidosis Initiative. Dr. Caplan reported no relevant financial relationships.

A version of this article appeared on Medscape.com .