Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post-hoc analysis aims to explore the efficacy of tofacitinib in patients (pts) with RA based on their baseline (BL) body mass index (BMI).

Methods: Data were analyzed from Phase 3 studies for pts who were methotrexate-naïve (NCT01039688) or had an inadequate response to DMARDs (NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385) who received ≥1 dose of tofacitinib 5 or 10 mg twice daily (BID) or placebo (PBO). Pts were stratified by BL BMI (<25, 25 to <30, ≥30). Efficacy endpoints (American College of Rheumatology [ACR]20/50/70 response rates at Month [M] 6; changes from baseline (Δ) in Health Assessment Questionnaire – Disability Index [HAQ-DI], Disease Activity Score in 28 joints by Erythrocyte Sedimentation Rate [DAS28‑4(ESR)], and Clinical Disease Activity Index [CDAI] at M3 and M6) were assessed.

Results: Overall, 1589, 1611, and 681 pts received tofacitinib 5 and 10 mg BID and PBO, respectively, with 1690, 1173, and 1017 pts in the BMI <25, 25 to <30, and ≥30 categories, respectively. BL demographics were generally similar between BMI categories with the exception of higher rates of diabetes (12.9–14.2 vs 3.5–9.8%), hypertension (53.2–58.9 vs 22.0–39.8%), and use of prior TNFi (23.7–46.8 vs 15.0–26.9%), and numerically higher tender (28.8–29.9 vs 23.5–26.9) and swollen joint counts (16.5–17.1 vs 14.5–16.3) and HAQ‑DI scores (1.6 vs 1.4–1.5) in the BMI ≥30 group vs BMI <25 or 25 to <30. In general, ACR response rates were significantly higher (p<0.05) in the tofacitinib vs PBO groups, regardless of BMI category (Figure 1). There appeared to be a trend towards lower ACR20/50/70 response rates with increasing BMI at M6 in tofacitinib- and PBO-treated pts; however, confidence intervals (CI) overlap. A trend for smaller ΔHAQ-DI through M6 with increasing BMI was observed only in pts receiving tofacitinib 5 mg BID, with overlapping CI (Figure 2A). The ΔDAS28‑4(ESR) and ΔCDAI scores were similar for tofacitinib- and PBO-treated pts regardless of BL BMI (Figure 2B–C). Generally similar trends were observed when stratified by weight.

Conclusion: Results of this post-hoc analysis suggest that tofacitinib is associated with improvements in RA outcomes compared with PBO regardless of BL BMI category. In both tofacitinib and PBO groups, similar trends in improvements were seen in most endpoints regardless of BMI category, implying that the effect of BL BMI is not specific to tofacitinib. Further investigation is needed to assess the degree of impact of BMI on tofacitinib efficacy.