Dados do Trabalho

Título

Corticosteroid-free efficacy and safety outcomes in patients receiving tofacitinib in the OCTAVE Sustain maintenance study

Introdução

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

Objetivo

We report corticosteroid-free efficacy and safety in patients (pts) who received corticosteroids at OCTAVE Sustain (NCT01458574) baseline.

Método

Pts who progressed to OCTAVE Sustain following clinical response (CR) in OCTAVE Induction 1&2, and who were receiving oral corticosteroids at OCTAVE Sustain baseline, were included. Corticosteroid tapering was mandatory in OCTAVE Sustain. Steroid-free (not requiring corticosteroid treatment for ≥4 weeks [wks] prior to the visit) remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding subscore [RBS] 0), endoscopic improvement (Mayo endoscopic subscore ≤1), and CR (decreased from induction baseline total Mayo score by ≥3 points and ≥30%, and a ≥1-point decrease in RBS or an absolute RBS ≤1) were assessed at Wk24 and/or Wk52. Association between baseline characteristics and steroid-free efficacy outcomes was evaluated by logistic regression. Safety outcomes were summarized by Wk52 steroid-free remission status.

Resultados

289/593 pts entering OCTAVE Sustain had baseline corticosteroid use; 101 (34.9%) received placebo and 188 received tofacitinib (101 [34.9%] 5mg BID; 87 [30.1%] 10mg BID). A significant (p<0.05) treatment effect of tofacitinib 5 or 10mg BID vs placebo was observed for all efficacy endpoints at Wk24 or Wk52. Wk52 rates of steroid-free remission, endoscopic improvement, and CR were 27.7%, 29.7%, and 40.6% in pts receiving tofacitinib 5mg BID; 27.6%, 29.9%, and 43.7% in pts receiving tofacitinib 10mg BID; and 10.9%, 11.9%, and 17.8% in pts receiving placebo (non-responder imputation). Prior immunosuppressant failure was associated with lower odds of achieving steroid-free remission at Wk52 (odds ratio [OR] 0.47; 95% confidence interval [CI] 0.23, 0.95), though prior tumor necrosis factor inhibitor (TNFi) failure status was not (OR 0.53; 95% CI 0.27, 1.02). Adverse events of special interest were infrequent. Discontinuations were numerically higher in pts without steroid-free remission.

Conclusão

Pts with baseline corticosteroid use in OCTAVE Sustain had significantly higher odds of achieving steroid-free efficacy endpoints with tofacitinib 5 or 10mg BID vs placebo. Prior TNFi failure did not impact odds of achieving steroid-free remission at Wk52. There were no differences in safety by steroid-free remission status. This study is limited by small pt numbers.

Palavras-Chave

Ulcerative colitis, Tofacitinib, Corticosteroids