Efficacy of Tofacitinib in Patients With Ulcerative Colitis by Prior Tumor Necrosis Factor Inhibitor Treatment Status: Results From OCTAVE Induction and Maintenance Studies

Abstract

Introduction: Many patients (pts) with ulcerative colitis (UC) treated with tumor necrosis factor inhibitors (TNFi) do not respond to initial therapy (primary non-response [NR]) or experience loss of response over time (secondary NR).1 Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated for UC. Methods: Pts in OCTAVE Induction 1 & 2 with moderately to severely active UC who failed or were intolerant to steroids, immunomodulators or TNFi received placebo (PBO; N=234) or tofacitinib 10 mg twice daily (BID; N=905) for 8 weeks (wks). In OCTAVE Sustain, induction study clinical responders were rerandomized to PBO (N=198), tofacitinib 5 mg BID (N=198) or 10 mg BID (N=197) for 52 wks. Corticosteroids were allowed in OCTAVE Induction; corticosteroid taper was mandatory in OCTAVE Sustain. Subgroup analyses by prior TNFi failure status were conducted for remission, mucosal healing and clinical response at Wk 8 (OCTAVE Induction; pooled data) and Wk 52 (OCTAVE Sustain), and sustained steroid-free remission among remitters at baseline of OCTAVE Sustain. Between-group treatment differences and 95% confidence intervals using the normal approximation were calculated, as well as p values based on chi-square test. Results: At Induction baseline, 51.7% of pts had failed TNFi (of whom 55.7% had primary NR, 39.2% secondary NR and 32.6% ≥2 failed TNFi). At Wk 8 of OCTAVE Induction, consistent treatment effects were observed with tofacitinib 10 mg BID vs PBO for all endpoints and categories of prior TNFi treatment status (Table). Observed treatment effects for remission, mucosal healing and clinical response were similar for pts with and without prior TNFi failure, and for pts who failed 1 TNFi and who failed ≥2 TNFi. In OCTAVE Sustain, treatment effects were observed at Wk 52 for 5 mg and 10 mg vs PBO for all endpoints and TNFi treatment categories. Treatment effects in OCTAVE Sustain were generally greater for 10 mg BID vs 5 mg BID, especially in pts with prior TNFi failure.Table: Table. Efficacy in OCTAVE Induction and OCTAVE Sustain Stratified by Prior TNFi Treatment StatusConclusion: Tofacitinib was efficacious vs PBO as induction and maintenance therapy, regardless of prior TNFi failure. Benefits over PBO were apparent even in the most refractory populations, including induction of remission in pts with primary NR, and pts who had failed ≥2 TNFi. Funded by Pfizer Inc. 1. Roda G et al. Clin Trans Gastroenterol 2016:e135.