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

• Published in: Advances in therapy 2023-10, Vol.40 (10), p.4440-4459
• Main Authors: Chiorean, Michael, Daperno, Marco, Lees, Charlie W., Bonfanti, Gianluca, Soudis, Dimitrios, Modesto, Irene, Deuring, J. Jasper, Edwards, Roger A.
• Format: Article
• Language: English
• Subjects: Cardiology; Clinical Trials, Phase III as Topic; Colitis, Ulcerative - drug therapy; Endocrinology; Humans; Internal Medicine; Janus Kinase Inhibitors - therapeutic use; Medicine; Medicine & Public Health; Oncology; Original Research; Pharmacology/Toxicology; Remission Induction; Rheumatology; Treatment Outcome
• ISSN: 0741-238X; 1865-8652; 1865-8652
• DOI: 10.1007/s12325-023-02603-0

Introduction 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. Methods Data from patients who participated in a 52-week, phase III maintenance study (OCTAVE Sustain) and an open-label long-term extension study (OCTAVE Open) were included in this analysis. Patients received tofacitinib 5 or 10 mg 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 week 8 of OCTAVE Sustain, steroid-free remission (defined as a partial Mayo score of 0–1 in the absence of corticosteroid use) at week 52 of OCTAVE Sustain, and delayed response at week 8 of OCTAVE Open. Furthermore, differences in loss of response/discontinuation patterns between treatment groups in OCTAVE Sustain were established. Results The generated prediction models demonstrated insufficient accuracy for determining loss of response at week 8, steroid-free remission at week 52 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). Conclusion 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. Graphical Abstract Plain Language Summary Doctors use tofacitinib (Xeljanz ® ) to treat people with moderate to severe ulcerative colitis. Patients who respond to (have improved symptoms following) treatment with tofacitinib 10 mg twice a day for 8 weeks, or up to 16 weeks if they do not respond initially (known as induction treatment), can receive tofacitinib treatment at the lowest effective dose to sustain th