High Body Mass Index is Associated with Shorter Retention of Tumor Necrosis Factor-Alpha Blocker Treatment in Rheumatoid Arthritis

Abstract

Purpose: To evaluate the association between body mass index (BMI) and tumor necrosis factor α (TNF-α) blockers retention in patients with rheumatoid arthritis (RA). Patients and Methods: This prospective cohort study analyzed data about patients with RA who initiated TNF blockers from the Israeli registry of inflammatory diseases from 2011 to 2019. Patients were grouped by BMI: normal (BMI <24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), obese (BMI 30-34.9 kg/m2) and morbid obese (BMI ≥35 kg/m2). Treatment cessation due to inefficacy was defined as an "event" and therapy with a drug above 3 months was defined as a "course." Kaplan-Meier survival curve was used to describe drug survival. Event-free survival was calculated using Cox regression with a hazard ratio and confidence interval of 95%. Results: The final analysis included 521 RA patients (80% females) treated with etanercept, infliximab, adalimumab or golimumab. Eight hundred and eighteen treatment initiations were included in the final analysis, 334 (41%) in the normal weight group, 261 (32%) in the overweight, 144 (17%) in the obese and 79 (10%) in the morbid obesity group. Three hundred and twenty-six (40%) treatment initiations were with etanercept, 215 (26%) with adalimumab 197 (24%) with infliximab, and 80 (10%) with golimumab. BMI was inversely associated with drug survival. Morbid obese patients were more likely to discontinue treatment compared with normal weight patients HR 2.28 (95% CI 1.67-3.10, p<0.01). This association remained significant for each drug type (except for golimumab) in a subgroup analysis. Adalimumab switch rate was higher compared to etanercept with HR =1.51 (95% CI 1.20-1.91, p<0.01), no other significant differences were noted between the other drugs. Conclusion: Morbid obese RA patients have lower TNF-α blocker retention compared to normal weight patients.

Age, Sex, Metabolic and Pharmacologic Factors May Predict Nonresponse Status to Rheumatoid Arthritis Therapies

“…There are few and scattered data related to BMI impact on the efficiency of proinflammatory cytokine inhibitors. However, there is strong evidence that high BMI reduces the efficiency of therapy with TNFα inhibitors and may induce nonresponse status (42,43). Bergstra et al (43) assessed TNFα inhibitors by stratifying patients into several BMI subcategories having more than 94% women.…”

Abolished TNF-α is crucial for the maintenance of B10 cells subsets in Psoriasis development

“…It can also promote the expression of MHC class I antigens on T cells and enhance the proliferation and Ig secretion of B lymphocytes stimulated by mitogen or foreign antigens, thus forming the pathological characteristics of excessive proliferation and abnormal differentiation of psoriatic keratinocytes [36]. TNFα also plays a key role in autoimmune diseases such as Crohn's disease, rheumatoid arthritis, and ankylosing spondylitis [37][38][39]. The level of serum TNFα may be related to the disease.…”

Obesity in rheumatoid arthritis: impact on response to biologic therapies

“…Three studies reported data for TNFi alone and had conflicting results. A large international register with follow-up centred at 5,000 days showed that both underweight patients and patients with a BMI over 35 were more likely to discontinue treatment with TNFi [67]. A smaller registry study involving 521 patients found that BMI was inversely associated with drug survival and those with a BMI more than 40 were over twice as likely to discontinue treatment compared with patients who have normal weight [68].…”