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Título

Evaluation of the efficacy of tofacitinib as maintenance therapy in patients with ulcerative colitis, stratified by OCTAVE Sustain baseline Mayo endoscopic subscore

Introdução

Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis.

Objetivo

To assess tofacitinib efficacy in OCTAVE Sustain (NCT01458574; 52-week [wk], Phase 3 maintenance study), by baseline Mayo endoscopic subscore (ES).

Método

In OCTAVE Sustain, responders from OCTAVE Induction 1&2 received tofacitinib 5 or 10mg twice daily (BID) or placebo; patients (pts) with an OCTAVE Sustain baseline ES of 0 or 1 were analysed. Proportions of pts achieving efficacy endpoints (Wk52) were evaluated by baseline ES; remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding subscore [RBS] 0), endoscopic improvement (Mayo ES ≤1), clinical response (CR; decrease from induction baseline total Mayo score by ≥3 points and ≥30%, and a ≥1-point decrease in RBS or an absolute RBS ≤1). Using logistic regression, treatment effect (tofacitinib vs placebo) differences between baseline ES (0 vs 1) for efficacy endpoints were assessed. Cox proportional hazards regression was used to model treatment effect differences between baseline ES (0 vs 1) for time to treatment failure and loss of response.

Resultados

Wk52 efficacy analyses included 255 pts (N=95 tofacitinib 5mg BID; N=75 10mg BID; N=85 placebo). Among 10mg BID-treated pts with baseline ES=0 (N=16), 75.0%, 75.0%, and 75.0% achieved remission, endoscopic improvement, and CR, respectively. Corresponding values for baseline ES=1 (N=59) were 54.2%, 62.7%, and 78.0%. For 5mg BID-treated pts, values were 61.9%, 66.7%, and 81.0% for ES=0 (N=21), and 36.5%, 40.5%, and 51.4% for ES=1 (N=74). Logistic regression analyses showed a larger treatment effect of tofacitinib 5mg BID at Wk52 in pts with baseline ES=0 vs ES=1 (p=0.0306) for CR. Treatment effects of tofacitinib 10mg BID were not significantly different between baseline ES=0 and ES=1 for any endpoint. In 5mg BID-treated pts, Cox proportional hazards regression showed a larger difference in risk vs placebo in pts with baseline ES=0 vs ES=1 for treatment failure (p=0.0231) and loss of response (p=0.0209); for 10mg BID-treated pts, ES=0 vs 1 differences were not significant (p=0.9239 and p=0.9613).

Conclusão

Treatment effects of tofacitinib 5mg BID were larger in pts with baseline ES=0 vs ES=1. Baseline ES may be important in predicting outcomes; findings suggest that aiming for deeper remission after induction may allow successful maintenance with tofacitinib 5mg BID. Analyses were post hoc and limited by sample size.

Palavras-Chave

JAK inhibitors, Ulcerative colitis, Tofacitinib

Área

Gastroenterologia - Intestino

Autores

Scott D Lee, Jessica R Allegretti, Flavio Steinwurz, Susan B Connelly, Nervin Lawendy, Jerome Paulissen, Krisztina B Gecse