IntroductionRheumatoid arthritis and its treatment have different effects on weight gain. This study examined the effect of tumor necrosis factor (TNF) inhibitors on weight gain in patients with seropositive rheumatoid arthritis compared with non-TNF therapy and disease activity. MethodsA retrospective cohort study was conducted in Prince Mohammad bin Abdulaziz Hospital for all patients aged ≥ 18-year-old diagnosed with seropositive rheumatoid arthritis and started on TNF inhibitors or non-TNF biologics in outpatient clinics since 2015. Patients were excluded if they were pregnant, had an uncontrolled underlying metabolic disease, were post-bariatric, or had a history of malabsorption. We also excluded individuals on treatment for congestive heart failure or end-stage renal disease. ResultsA total of 116 patients with rheumatoid arthritis were reviewed between 2015 and 2019. Only 69 patients met the inclusion criteria (51 and 18) in the TNF-a (alpha) and non-TNF-a inhibitor groups, respectively. The weight change from pre-treatment to post-treatment showed an average increase of 1.2 kg (95% CI: -0.68-3.17) in the TNF-a inhibitor group while in the non-TNF-a inhibitor group, the average increase in weight was 2.67 kg (95% CI: -0.44-5.78). Over the period of two years, there was no statistical difference in weight gain in both groups or in relation to disease activity. ConclusionThe results of this study did not show a significant increase in weight gain in seropositive patients with rheumatoid arthritis who were treated with TNF or non-TNF inhibitors.