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P388 Analysis of the impact of body mass index on efficacy and safety in the tofacitinib OCTAVE ulcerative colitis programme

F. A. Farraye1, T. Qazi1, P. G. Kotze*2, G. T. Moore3,4, C. Kayhan5, R. Mundayat5, E. Maller5, C. Su5, A. Soonasra5

1Boston Medical Center, Section of Gastroenterology, Boston University School of Medicine, Boston, MA, USA, 2Cajuru University Hospital, Pontifical Catholic University of Paraná (PUCPR), IBD Outpatient Clinics, Colorectal Surgery Unit, Curitiba, Brazil, 3Monash Health, Department of Gastroenterology, Melbourne, VIC, Australia, 4Monash University, School of Clinical Sciences at Monash Health, Melbourne, VIC, Australia, 5Pfizer Inc., Collegeville, PA, USA

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 for the treatment of UC. We present analysis of BMI effect on tofacitinib efficacy and safety in the tofacitinib UC clinical programme.

Methods

Data from two identical, 8-week (week) induction studies (OCTAVE Induction 1 and 2, NCT01465763 and NCT01458951)2 and a 52-week maintenance study (OCTAVE Sustain, NCT01458574)2 were analysed. 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 (Induction 1 and 2) and Week 52 (Sustain) for efficacy endpoints remission, clinical response and mucosal healing (MH), 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 Induction 1 and 2 and Sustain, tofacitinib-treated patients had a gradual increase in body weight and BMI over time vs. placebo. In Induction 1 and 2, for tofacitinib 10 mg BID at Week 8, patients with BMI <25 had numerically higher proportions of remission vs. other BMI groups. Proportion of patients with MH was lower in BMI ≥30. Clinical response was similar in all BMI groups. At Sustain Week 52, for tofacitinib 5 mg BID, BMI 25–<30 had highest proportions of remission and MH; BMI ≥30 had highest proportion of sustained steroid-free remission and lowest proportion for MH and clinical response vs. other BMI groups. Clinical response was similar for all BMI groups. In Sustain, for tofacitinib 10 mg BID, BMI ≥30 had highest proportions of remission, sustained steroid-free remission, MH, and clinical response. For tofacitinib patients in Induction 1 and 2, opportunistic infections (OI) were rare; proportions were similar across BMI groups. BMI stratification for infections and serious infections (SI) was not available. In Sustain, for tofacitinib 5 and 10 mg BID, infections were numerically higher for BMI 25–<30 vs. others. There were few OI or SI, and proportions were similar among subgroups.

Conclusion

The majority of patients with UC in the OCTAVE programme 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 OI/SI events.

Abstract P388 – Table. Summary of safety sad efficacy outcomes for patients in the Phase 3 OCTAVE Induction 1 and 2 and OCTAVE Sastain studies, stratified by BMI (FAS, NRI).

References

1. Kurnool S, Nguyen NH, Proudfoot J, et al. High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis. Aliment Pharmacol Ther 2018;47:1472–9. doi:10.1111/apt.14665

2. Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2017;376:1723–36. doi:10.1056/NEJMoa1606910