Background
Tofacitinib is a rapidly acting Janus kinase (JAK) inhibitor with several case series reporting effectiveness in patients with acute severe ulcerative colitis (ASUC). However, there remains a paucity of prospective data evaluating its efficacy and rapidity of onset in ASUC.
Methods
The TRIUMPH study is a phase 4 prospective interventional trial of tofacitinib in ASUC conducted in five hospitals across Canada (Clinicaltrials.gov: NCT04925973). Patients with ASUC (biologic naïve and experienced) refractory to three days of intravenous corticosteroids (Modified Truelove-Witts Severity Index [MTWSI] > 10 despite steroids) were eligible for enrollment. Patients were treated with tofacitinib 10mg bid and assessed daily while in hospital. The primary outcome was day 7 clinical response (MTWSI reduction of > 3 from baseline and < 10). Secondary outcomes included rapidity of clinical and biomarker improvements over the first 7 days, colectomy over the course of one year, and corticosteroid-free clinical remission (total Mayo score < 2), endoscopic improvement (endoscopic Mayo score 0 or 1), and adverse events at 3, 6, and 12 months.
Results
This is an interim analysis as the study has been fully recruited with six-month follow-up available for all participants. 24 patients with ASUC were recruited and received tofacitinib 10mg bid. The mean total baseline Mayo score was 10.1 (SD 1.4) and all patients had a baseline Mayo endoscopic subscore of 2 (25%, 6/24) or 3 (75%, 18/24). One third of the patients (8/24) had previous anti-TNF failure. Day 7 clinical response was achieved in 58.3% (14/24) patients. The mean number of days to achieve clinical response was 2.4 days (SD 1.3). Marked reduction in C-reactive protein was observed in responders as soon as one day after tofacitinib initiation compared to non-responders (Figure 1). Colectomy occurred in 16.7% (4/24) patients by day 7 and 25% (6/24) by six months. At six months, 45.8% (11/24) patients remained on tofacitinib (including 78.6% (11/14) of day 7 responders), with 33.3% (8/24) having achieved endoscopic improvement and corticosteroid-free clinical remission. A total of six patients reported adverse events, one of which was considered severe (stroke at day 3 after initiation of tofacitinib).

Conclusions
Tofacitinib may be an effective induction strategy in patients hospitalized with steroid-refractory ASUC. Randomized controlled trials are needed to compare JAK inhibitors with infliximab for steroid refractory ASUC.

Figure 1 – Daily mean CRP trends for tofacitinib responders vs non-responders. Treatment responders are those who had a 3 or more-point reduction in MTWSI by day 7 and a total score of ≤ 10. P-value of 0.003 when comparing slope of lines for responders (blue) and non-responders (orange) by ANCOVA test.

Jane Castelli

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