Tofacitinib Has Induction Efficacy in Moderately to Severely Active Ulcerative Colitis, Regardless of Prior TNF Inhibitor Therapy

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated for ulcerative colitis (UC). Two Phase 3 randomized placebo (PBO)-controlled studies (OCTAVE Induction 1 and 2: NCT01465763, NCT01458951) demonstrated efficacy of tofacitinib 10 mg twice daily (BID) vs PBO as induction therapy for patients (pts) with moderate to severe UC.1 Here, we assessed the effect of TNF inhibitor (TNFi) therapy and disease severity on clinical efficacy and patient-reported outcomes (PROs). Methods: Adults with moderately to severely active UC (Mayo score ≥6, rectal bleeding subscore ≥1 and endoscopic subscore ≥2) and prior failure/intolerance to ≥1 of corticosteroids, thiopurines or TNFi were randomized (4:1) to receive tofacitinib 10 mg or PBO BID for up to 9 weeks (wks). Efficacy endpoints at Wk 8 included: remission (Mayo score ≤2, no subscore >1 and rectal bleeding subscore of 0), mucosal healing at Wk 8 (Mayo endoscopic subscore ≤1), clinical response (decrease from baseline Mayo score of ≥3 points and ≥30%, plus decrease in rectal bleeding subscore ≥1 or absolute subscore ≤1). PROs at Wk 8 included IBDQ remission (total score ≥170) and IBDQ response (≥16-point increase from baseline). For binary endpoints, comparison of tofacitinib vs PBO was assessed using the Cochran-Mantel-Haenszel (CMH) chi-square test stratified by study, prior TNFi therapy, baseline corticosteroid use and geographic region. Within each subgroup, the CMH chi-square test stratified by study was used.Table 1: Summary of efficacy endpoints in OCTAVE Induction 1 and OCTAVE Induction 2 at Wk 8Results: Significantly more pts achieved remission, mucosal healing and clinical response at Wk 8 with tofacitinib 10 mg BID vs PBO (all p < 0.0001).The difference generally remained significant regardless of prior TNFi exposure, prior TNFi failure, primary or secondary TNFi failure or baseline Mayo score (≥9 or < 9). For all three endpoints, greater effects were observed when comparing secondary vs primary TNFi failure and baseline Mayo score < 9 vs ≥9 subpopulations. IBDQ remission and response were significantly greater with tofacitinib 10 mg BID vs PBO at Wk 8 regardless of prior TNFi exposure/prior TNFi failure. Conclusion: Tofacitinib 10 mg BID demonstrated efficacy vs PBO, regardless of prior TNFi therapy or baseline disease severity, in pts with moderately and severely active UC. PRO results were similar in pts with/without prior TNFi exposure or failure. Funded by Pfizer Inc. 1. Sandborn WJ et al. J Crohns Colitis 2016;10(S1):S15.

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