ANALYSIS OF THE IMPACT OF BODY MASS INDEX ON EFFICACY AND SAFETY IN THE TOFACITINIB OCTAVE ULCERATIVE COLITIS PROGRAM

Background: High body mass index (BMI) can be associated with increased risk of treatment failure in biologic-treated patients with ulcerative colitis (UC).1 Tofacitinib is an oral, small molecule JAK inhibitor approved in several countries, including the US, for the treatment of UC. We present analysis of BMI effect on tofacitinib efficacy and safety in the tofacitinib UC clinical program. Methods: Data from two identical, 8-week induction studies (OCTAVE Induction 1 & 2, NCT01465763 & NCT01458951)2 and a 52-week maintenance study (OCTAVE Sustain, NCT01458574)2 were analyzed. Patients received placebo, tofacitinib 5 or 10 mg twice daily (BID). Patients were stratified by BMI <25, 25?<30, or ≥30 for analysis at Week 8 (OCTAVE Induction 1&2) and Week 52 (OCTAVE Sustain) for efficacy endpoints remission, clinical response, and mucosal healing, and for safety outcomes including infections. Results: Patient demographics and baseline characteristics were similar for placebo and tofacitinib groups. The majority of patients in each group had BMI <25 (Table). In OCTAVE Induction 1 & 2 and OCTAVE Sustain, tofacitinib treated-patients had a gradual increase in body weight and BMI over time vs placebo. In OCTAVE Induction 1 & 2, for tofacitinib 10 mg BID at Week 8, patients with BMI <25 had numerically higher proportions of remission vs other BMI groups. The proportion of patients with mucosal healing was lower in BMI ≥30. Clinical response was similar in all BMI groups. At OCTAVE Sustain Week 52, for tofacitinib 5 mg BID, BMI 25?<30 had the highest proportions of remission and mucosal healing; BMI ≥30 had the highest proportion of sustained steroid-free remission and the lowest proportion for mucosal healing and clinical response, vs other BMI groups. Clinical response was similar for all BMI groups. In OCTAVE Sustain, for tofacitinib 10 mg BID, BMI ≥30 had the highest proportions of remission, sustained steroid-free remission, mucosal healing, and clinical response. For tofacitinib patients in OCTAVE Induction 1 & 2, opportunistic infections were rare; proportions were similar across BMI groups. BMI stratification for infections and serious infections was not available. In OCTAVE Sustain, for tofacitinib 5 and 10 mg BID, infections were numerically higher for BMI 25?<30 vs others. There were few opportunistic or serious infections, and proportions were similar among subgroups. Conclusion: The majority of patients with UC in the OCTAVE program had BMI <25. In subgroup analyses by BMI, patients with high BMI receiving tofacitinib did not demonstrate lower efficacy endpoints or greater infection rates. However, limitations include low patient numbers in the BMI ≥30 group and rare opportunistic/serious infection events. References: 1. Kurnool et al. Aliment Pharmacol Ther 2018;47:1472-9. 2. Sandborn et al. N Engl J Med 2017;376:1723-36. [Table Presented]