Presence of Risk Factors Associated with Colectomy in Patients with Ulcerative Colitis in Studies with Tofacitinib
One of the important goals of active ulcerative colitis therapy is the prevention of colectomy. A clinical study, the results of which were recently presented at the Vienna UEG (United European Gastroenterology) congress, evaluated the association of risk factors and the use of tofacitinib with colectomy in patients with active ulcerative colitis in the OCTAVE clinical trial program.
Introduction
Tofacitinib is a selective Janus kinase (JAK) inhibitor indicated for the treatment of moderately to severely active ulcerative colitis (UC) in adult patients. Its main mechanism of action is the intracellular inhibition of the JAK/STAT signaling pathway, thereby reducing the production of pro-inflammatory cytokines.
Study Methodology
Post hoc analysis of data from the OCTAVE clinical program with tofacitinib evaluated baseline characteristics and the presence of colectomy risk factors in patients with active UC. Colectomy procedures were assessed in 3 patient cohorts: the induction cohort (tofacitinib 10 mg twice daily or placebo), the maintenance cohort (tofacitinib 5 or 10 mg twice daily or placebo), and the overall cohort (patients who received at least one dose of tofacitinib 5 or 10 mg in the phase III clinical study or in the long-term open extension).
Evaluated risk factors for colectomy included age at diagnosis < 40 years, extensive colitis, endoscopically verified severe disease (Mayo endoscopic subscore 3), hospitalization for colitis in the last 12 months, C-reactive protein (CRP) level > 3 mg/l, and serum albumin < 35 g/l.
Results
A total of 14 patients underwent colectomy. The procedure was performed in 3 patients in the induction cohort (n = 1139), with 2 on tofacitinib and 1 on placebo, in 3 patients in the maintenance cohort (n = 593), all of whom were on placebo, and finally in 8 patients in the open extension (n = 944), all of whom were taking tofacitinib 10 mg twice daily and were not in remission upon entering this extension study.
The number of colectomies per 100 patient-years was 2.47 in the induction cohort on placebo and 1.26 on tofacitinib, 2.90 in the maintenance cohort on placebo and 0 in patients on tofacitinib 5 or 10 mg, and in the overall study group, it was 0.34 across all tofacitinib dosing regimens.
All patients who underwent colectomy had at least one monitored risk factor present at the time of study enrollment and had previously been treated with tumor necrosis factor inhibitors (TNFi).
Conclusion
In the OCTAVE clinical trial program, colectomy was an infrequent surgical procedure relative to the total number of patients. All patients who underwent colectomy had a history of TNFi therapy and at least one colectomy risk factor. The lower proportion of colectomies in patients on tofacitinib in the induction cohort and the fact that no colectomy was performed during the maintenance phase in patients on tofacitinib support the importance of continuous active therapy in patients with moderately to severely active ulcerative colitis.
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Source: Rubin D. T., Salese L., Kotze P. G. et al. Presence of risk factors associated with colectomy among patients with colectomy in the tofacitinib OCTAVE ulcerative clinical programme. UEG Week, Vienna, 2022 Oct 8−11.
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