Tofacitinib for Acute Severe Ulcerative Colitis: A Systematic Review

BACKGROUND: Tofacitinib has emerged as a new potential treatment for acute severe ulcerative colitis [ASUC]. We conducted a systematic review to assess efficacy, safety and integration in ASUC algorithms.

METHODS: Systematic searching was done in MEDLINE, EMBASE, Cochrane Library and Clinicaltrials.gov until August 17, 2022, including all studies reporting original observations on tofacitinib for ASUC, preferably defined according to Truelove and Witts criteria. The primary outcome was colectomy-free survival.

RESULTS: Of 1072 publications identified, 21 studies were included of which three were ongoing clinical trials. The remaining comprised a pooled cohort originating from 15 case publications [n = 42], a GETAID cohort study [n = 55], a case-control study [n = 40 cases] and a paediatric cohort [n = 11]. Of these 148 reported cases, tofacitinib was used as second-line treatment after steroid failure in previous infliximab failures or third-line after sequential steroid and infliximab or cyclosporine failure, 69 [47%] were female, median age range was 17-34 years and disease duration was 0.7-10 years. Overall, 30-day colectomy-free survival was 85% [n = 123 of 145; n = 3 without colectomy had follow-up <30 days], 90-day 86% [n = 113 of 132; n = 16 follow-up <90 days] and 180-day 69% [n = 77 of 112; n = 36 follow-up <180 days]. Tofacitinib persistence at follow-up was 68-91%, clinical remission 35-69% and endoscopic remission 55%. Adverse events occurred in 22 patients, predominantly being infectious complications other than herpes zoster [n = 13], and resulted in tofacitinib discontinuation in seven patients.

CONCLUSION: Tofacitinib appears promising for treatment of ASUC with high short-term colectomy-free survival among refractory patients who are otherwise deemed to require colectomy. However, large high-quality studies are needed.