In a poster presentation from ACR Convergence 2024, researchers reported findings of a study to evaluate the effects of metabolic syndrome on response to biologic therapies among patients with rheumatoid arthritis (RA).

Joshua F. Baker, MD, MS, from the University of Pennsylvania in Philadelphia, presented the abstract on behalf of himself and his research colleagues.

While body mass index (BMI) has been associated with response to therapy in several studies in RA, it is not a comprehensive measure of the metabolic consequences of obesity, the investigators noted. Their study set out to determine how the individual components of metabolic syndrome— central adiposity, hypertension, lipid abnormalities, and insulin resistance—and adipokines—adiponectin, leptin, Fibroblast Growth Factor-21— were associated with response to therapies, including both tumor necrosis factor inhibitors (TNFis) and non-TNFis.

Participants included those with RA who demonstrated at least moderate disease activity and began therapy with either TNFi or non-TNFi biologic therapies. These patients were drawn from the Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) cohort within the CorEvitas registry. The researchers defined metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III definition. Adipokines were assessed on stored samples from a subsample of responders and nonresponders to both TNFi and non-TNFi therapies (N=200).

The primary outcome was a change as large as the minimal clinically important difference (MCID) for the Clinical Disease Activity Index (CDAI) at 6 months. Low disease activity, defined as CDAI< 10, was a secondary outcome.

Among 2368 participants, 687 (29%) had metabolic syndrome, which was associated with lower odds of achieving CDAI MCID [OR: 0.69 (95% CI: 0.56,0.86) p=0.001]. All components of metabolic syndrome, with the exception of hypertension, were associated with lower odds of achieving MCID, and with low disease activity (LDA).

The response rate showed a dose-dependent reduction according to the number of metabolic syndrome components present. Only patients with underweight BMI or severe obesity were found to have lower odds of response compared to patients with normal BMI independent of metabolic syndrome [OR (underweight): 0.24 (95% CI: 0.075,0.77), p=0.02]. Associations between metabolic syndrome and response were similar between patients receiving TNFi and non-TNF therapies ([OR: 0.65 (95% CI: 0.49,0.87) p=0.003] v. [OR: 0.76 (95% CI: 0.55,1.04), p=0.08] (p-for-interaction=0.49). While adipokines were each associated with metabolic syndrome, they did not show an association with the achievement of MCID.

The investigators concluded that metabolic aspects of obesity, independent of weight alone, are important in patient response to advanced therapies in RA. Adipokines were associated with metabolic syndrome but not with clinical response, suggesting they do not play a mediating role. These associations have implications for trial design and clinical practice, though further study is needed to define the underlying mechanisms.

Baker J, Reed G, Thiele G, et al. 0457: Metabolic Syndrome, Adipokines, and Response to Advanced Therapies in Rheumatoid Arthritis. Presented at: American College of Rheumatology Convergence. November 16, 2024. Washington, DC