Despite research into the connection between body mass index (BMI) and clinical response to treatments, it remains difficult for physicians to predict which patients with rheumatoid arthritis (RA) will have refractory disease and demonstrate a poor response to therapy.
Prior research demonstrated that patients with RA and abnormally low weight or obesity per the BMI were less likely to achieve a meaningful clinical response to biologic disease-modifying therapies. However, there was no evidence that a tumor necrosis factor (TNF) inhibitor vs. a non-TNF inhibitor advanced therapy would work better than the other for these patients. Thus, despite its association with treatment response, BMI may not be a comprehensive measure of the metabolic consequences of obesity, and few RA studies have evaluated metabolic syndrome (i.e., central adiposity, hypertension, lipid abnormalities and insulin resistance) and its effects on RA disease activity.
In their current study, Baker et al. investigated whether metabolic syndrome and high levels of adiponectin, leptin and fibroblast growth factor (FGF) 21 are associated with response to advanced therapies among patients with RA.
Methods
Using data from the Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions cohort within the CorEvitas registry, the study included patients with RA initiating either TNF inhibitor or non-TNF inhibitor biologic therapy. Researchers defined metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III, which requires three of the following criteria:
- A waist circumference of >40 inches (men) or >35 inches (women);
- A blood pressure of >130/85 mm Hg or a diagnosis of hypertension;
- A fasting triglyceride level of >150 mg/dL;
- A non-fasting, high-density lipoprotein cholesterol level of <40 mg/dL (men) or <50 mg/dL (women); and
- A fasting blood glucose level >100 mg/dL or a history of diabetes.
The researchers also examined adipokines, which serve as metabolic regulators strongly associated with obesity and its complications. Adipokines were assessed on stored samples from a subsample of treatment responders and nonresponders.
The Results
Among the 2,368 study participants, 29% had metabolic syndrome. The overall rate of response to therapy was 56% in patients without metabolic syndrome and 48% in patients with metabolic syndrome.
At six months, metabolic syndrome was associated with lower odds of patients achieving minimal clinically important difference (MCID) for the Clinical Disease Activity Index (CDAI) (odds ratio 0.69, 95% confidence interval 0.56–0.86, P=0.001) with a dose-dependent decrease in response rate according to the number of components present. Associations between metabolic syndrome and MCID achievement were also similar between patients receiving TNF inhibitors and those receiving non-TNF inhibitor therapies. Adipokines were not associated with MCID achievement.
Additionally, the model fit for metabolic syndrome was superior compared with BMI alone, suggesting metabolic syndrome is more informative to clinical response than a simple assessment of weight or BMI.
Conclusion
In patients with RA, metabolic syndrome was associated with lower response rates to the initiation of an advanced RA therapy, with similar effects for both TNF inhibitor and non-TNF inhibitor treatments.
For complete details, including source material, refer to the full study.
Excerpted and adapted from:
Baker JF, Reed G, Mikuls TR, et al. Metabolic syndrome, adipokines and response to advanced therapies in rheumatoid arthritis. Arthritis Rheumatol. 2025 Mar;77(3).
