Modeling of Treatment Outcomes with Tofacitinib Maintenance Therapy in Patients with Ulcerative Colitis: A Post Hoc Analysis of Data from the OCTAVE Clinical Program.

Abstract

Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). This post hoc analysis assessed whether various statistical techniques could predict outcomes of tofacitinib maintenance therapy in patients with UC. Data from patients who participated in a 52-week, phaseIII maintenance study (OCTAVE Sustain) and an open-label long-term extension study (OCTAVE Open) were included in this analysis. Patients received tofacitinib 5 or 10mg twice daily (BID) or placebo (OCTAVE Sustain only). Logistic regression analyses were performed to generate models using clinical and laboratory variables to predict loss of responder status at week8 of OCTAVE Sustain, steroid-free remission (defined as a partial Mayo score of 0-1 in the absence of corticosteroid use) at week52 of OCTAVE Sustain, and delayed response at week8 of OCTAVE Open. Furthermore, differences in loss of response/discontinuation patterns between treatment groups in OCTAVE Sustain were established. The generated prediction models demonstrated insufficient accuracy for determining loss of response at week8, steroid-free remission at week52 in OCTAVE Sustain, or delayed response in OCTAVE Open. Both tofacitinib doses demonstrated comparable response/remission patterns based on visualizations of disease activity over time. The rectal bleeding subscore was the primary determinant of disease worsening (indicated by an increased total Mayo score), and the endoscopy subscore was the primary determinant of disease improvement (indicated by a decreased total Mayo score). Visualizations of disease activity subscores revealed distinct patterns among patients with UC that had disease worsening and disease improvement. The statistical models assessed in this analysis could not accurately predict loss of responder status, steroid-free remission, or delayed response to tofacitinib. Possible reasons include the small sample size or missing data related to yet unknown key variables that were not collected during these trials.