Adalimumab, a fully human anti-TNFα monoclonal antibody, is effective in treating rheumatoid arthritis (RA). However, obesity is highly prevalent among RA patients and may affect drug pharmacokinetics and clinical outcomes. This review summarizes current research on the interaction between obesity and adalimumab treatment in RA.

A narrative review of published studies examining adalimumab pharmacokinetics, efficacy, and clinical outcomes in obese versus non-obese RA patients, including post-hoc analyses, cohort studies, and mechanistic investigations.

Epidemiological data show that obesity is associated with an increased risk of developing RA (OR 1.24, 95% CI 1.01-1.53) and lower remission rates (pooled OR 0.57, 95% CI 0.45-0.72). In a post-hoc analysis of the MUSICA trial, obese RA patients treated with adalimumab and methotrexate showed numerically smaller improvements from baseline to weeks 12/24 in swollen/tender joint counts, DAS28-CRP, and synovial vascularity compared to non-obese patients. Significantly fewer obese patients achieved ACR20/50 at weeks 12 and 24, and low disease activity at week 12, although the latter difference was not significant at week 24. In patients with ankylosing spondylitis, obesity was linked to significantly lower serum adalimumab levels and reduced clinical response. Potential mechanisms include altered drug distribution due to increased adipose tissue (estimated apparent volume of distribution 10.8 L in RA patients), adipokine dysregulation (e.g., higher leptin levels correlate with disease activity), microbiome alterations, and non-coding RNA changes (e.g., miR-21, miR-146a, H19). Diagnostic challenges are also notable: the positive predictive value of clinically assessed swollen joints for true synovitis drops from 0.71 in normal-weight patients to 0.44 in those with BMI >30. Biomarkers such as CD11c (100% sensitivity, 91.7% specificity for predicting adalimumab response) and regulatory T cells have shown promise for monitoring treatment response in obese RA patients.

Obesity negatively impacts adalimumab efficacy in RA, though some differences may diminish over time. Current guidelines lack specific recommendations for dose adjustment or therapy selection in obese RA patients. Future research should focus on personalized medicine approaches, validated biomarkers (e.g., CD11c, regulatory T cells), and optimized dosing strategies for this growing patient population.