Obesity and Response to Advanced Therapies in Rheumatoid Arthritis

Abstract

Objective We performed a study of tumor necrosis factor inhibitors (TNFi) compared to non‐TNFi biologic therapies in rheumatoid arthritis to test whether body mass index (BMI) modified the effect of each therapy. Methods We utilized data from CorEvitas. We studied 3 clinical outcomes based on the Clinical Disease Activity Index (CDAI) at 6 months from therapy initiation: 1) achievement of low disease activity (LDA); 2) a change as large as the minimum clinically important difference (MCID); and 3) the absolute change. We categorized BMI and utilized restricted cubic splines to consider nonlinear associations. We used linear and logistic regression to evaluate associations with response, adjusting for confounders. To determine if comparative effectiveness of therapy varied by BMI, we tested for interactions between BMI and class of therapy. Results The sample included 2,891 TNFi and 3,010 non‐TNFi initiators. Among all initiators, those with severe obesity experienced lower odds of achieving LDA or MCID and less improvement in CDAI score, although associations were attenuated with adjustment. Low BMI was associated with reduced response rates in adjusted models including lower odds of LDA (odds ratio 0.32 [95% confidence interval (95% CI) 0.15, 0.71], P = 0.005). Analyses stratified by TNFi and non‐TNFi therapies demonstrated no differences in clinical response rates for TNFi versus non‐TNFi across BMI categories (all P for interaction >0.05). Estimates for non‐TNFi biologics fit within the 95% CI for TNFi. Conclusion This study observed lower response rates among obese and underweight patients and no evidence of a superior effect of non‐TNFi therapy over TNFi therapy in particular BMI categories.

Cardiovascular Risk Factors and the Risk of Discontinuation of Advanced Therapies Due to Treatment Failure in Rheumatoid Arthritis: Results From the Ontario Best Practices Research Initiative

“…To the best of our knowledge, there have been no prior studies investigating the influence of the number of CVD risk factors on discontinuation of b/tsDMARDs for different types of treatment failure in patients with RA. Previous reports have suggested that certain individual risk factors, such as obesity and smoking, can diminish the response to targeted therapies 10,14 . However, it remains uncertain whether this association is specific to primary or secondary treatment failure or an increased likelihood of experiencing side effects.…”

Obesity, sarcopenia, and arthritis and the theory of relativity: comment on the article by Baker et al

“…The authors also ask "is rheumatoid sarcopenia a consequence of a more aggressive disease, and therefore, more difficult to treat…?" (1). We believe that the answer is quite likely yes.…”

“…With these comments, we hope that Dr. Dixit and other individuals who might have similar concerns can better understand the rationale for the strategies undertaken. (1), because rather than suggesting that obesity reduces the therapeutic response rate of patients with rheumatoid arthritis (RA) to both anti-tumor necrosis factor (TNF) and non-TNF therapies, the article adds that this problem is also related to underweight.…”

Mitochondrial Dysfunction and Oxidative Stress in Rheumatoid Arthritis

“…Anti-TNF therapy reduces insulin resistance and improves insulin sensitivity in patients with severe RA. New findings have shown, however, that the efficacy of these agents in this regard is impaired by obesity [ 245 , 246 , 247 ].…”