P583 Tofacitinib for acute severe ulcerative colitis: a systematic review

Abstract

Abstract Background Treatment of acute severe ulcerative colitis (ASUC) comprising iv steroids, second line infliximab or cyclosporin, and finally colectomy, has remained unchanged for nearly two decades and without improvements in colectomy rates. Tofacitinib (TOFA), a pan JAK-inhibitor, has emerged as a potential new treatment option for ASUC. We conducted a systematic review to assess efficacy, safety, and integration in current ASUC algorithms. Methods Systematic search in MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Clinicaltrials.gov until August 17, 2022, including all studies reporting original observations on JAK-inhibitor use, notably tofacitinib, for ASUC defined according to Truelove and Witts criteria. Primary outcome was colectomy-free survival. Individual patient data from case reports were pooled and collectively analyzed. Results Of 853 publications identified, 20 studies (seven single case reports and eight case series resulting in data from 42 patients; one combined retrospective and prospective GETAID cohort study of 55 patients; one retrospective study of 40 cases and 113 matched controls; one pediatric retrospective cohort study of 11 patients; two ongoing trials) involving 148 patients (female 44-60%, age median 28-34 years, disease duration 5-10 years) treated with second- or third line tofacitinib for ASUC were included. Colectomy-free survival was 78% from 90-day onwards in the pooled cohort of individual cases (Figure); GETAID cohort 85% 30-day, 79% 90-day, 74% 180-day; and 63% in the pediatric cohort. The case-control study observed lower 90-day colectomy risk among TOFA treated (HR 0.28 [0.10-0.28], p=0.018). The majority received second line TOFA rescue therapy after initial failure to iv steroids (n=65), and with previous failure to one or more biologics, notable infliximab (n=62, 95%). There was no difference in colectomy rates between patients treated with second or third line TOFA (n=15 (23%) vs. n=1 (8%), p=0.44). Tofacitinib persistence at follow-up was 68-91%, clinical remission 35-69%, endoscopic remission 55%, and without reports of novel or severe safety signals (Table). Conclusion Tofacitinib appears to result in high short-term colectomy-free survival among refractory ASUC patients and may have potential in the future treatment of patients otherwise deemed for colectomy. Efficacy was comparable to first line ASUC therapy with iv steroids, but observations are limited, uncontrolled and with short follow-up. High-quality studies are needed.