Metabolic Syndrome, Adipokines, and Response to Advanced Therapies in Rheumatoid Arthritis

Objective: We determined if metabolic syndrome, its components, and adipokines (adiponectin, leptin, and fibroblast growth factor-21) were associated with response to advanced therapies among patients with rheumatoid arthritis (RA). Methods: This study included participants with RA initiating either tumor necrosis factor inhibitor (TNFi) or non-TNFi biologic therapies from the Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) cohort within the CorEvitas registry. Metabolic syndrome was defined 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 (n = 200). The primary outcome was the achievement of a change as large as the minimal clinically important difference (MCID) for the Clinical Disease Activity Index (CDAI) at 6 months. Results: Among 2,368 participants, 687 (29%) had metabolic syndrome. Metabolic syndrome was associated with lower odds of achieving CDAI MCID (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.56–0.86, P = 0.001) with a dose-dependent decrease in response rate according to the number of components present. Model fit was superior for metabolic syndrome compared with body mass index. Associations between metabolic syndrome and MCID achievement were similar between patients receiving TNFi (OR 0.65, 95% CI 0.49–0.87, P = 0.003) versus non-TNF therapies (OR 0.76, 95% CI 0.55–1.04, P = 0.08 [P for interaction = 0.49]). Adipokines were not associated with MCID achievement. Conclusion: Metabolic syndrome is associated with lower response rates with the initiation of an advanced therapy in RA, with similar effects for both TNFi and non-TNFi agents. Adipokines were strongly associated with metabolic syndrome but were not associated with clinical response.