P586 Tofacitinib for the induction and maintenance of medically resistant ulcerative colitis

Abstract

Background: Many inflammatory bowel disease (IBD) patients are unresponsive to medical therapy or lose response, mainly in the first year of treatment. Tofacitinib is an oral, non-selective inhibitor of the Janus kinase (JAK) family, focused mainly at JAK 1 and 3. Its effectiveness for rheumatoid arthritis, psoriasis and for induction and maintenance of remission of ulcerative colitis (UC) has been demonstrated in recent pivotal trials. Here we describe our off-label experience with the use of tofacitinib for treatment refractory moderate-to-severe IBD patients. Methods: This is a retrospective observational study of the off-label use of tofacitinib for IBD in a single tertiary medical centre. Patients with medically resistant IBD were treated with tofacitinib at 5 or 10 mg BID. Clinical response and adverse events were assessed at 8 weeks (induction), at 26 weeks (maintenance), and at the last follow-up available. Response to treatment was determined as defined by the patient's provider, combined with the decision to continue therapy. Response was defined as symptomatic improvement but not resolution, and remission was defined as complete resolution of clinical symptoms. Results: Between December 2014 and 2017, 23 IBD patients [21 UC, 2 CD (colon), 14 male; median age 38.7 (IQR 29-48)] were treated with tofacitinib. All patients but one (95.4%) had failed treatment with anti-TNF and 17 (74%) previously failed antiintegrin. The initial dose was 5 mg BID for 16 patients and 10 mg BID for 7. At 8 weeks of treatment, 18 patients (78%) achieved clinical response, with 7 (30%) achieving remission. Sixteen of the 18 patients were steroid free at Week 8. Thirteen out of the 18 responsive patients (72%), maintained their response by Week 26. 10 (55%) were steroid free at that point. By the end of median 43 weeks follow-up (range 13-73 weeks), 14 patients (60%) were still responsive to the drug (Figure). Two episodes of systemic infections were noted, both while on concomitant steroids: cellulitis and parainfluenza which required hospitalisation and cessation of treatment. Two patients had increased cholesterol levels, none required medical intervention. No other adverse effects were observed. No episodes of zoster infections were noted during follow-up. Conclusions: In this cohort of medically resistant IBD patients, 78% of them responded to off-label tofacitinib and most of them remained responsive during median follow-up of 43 weeks. Tofacitinib is an effective therapeutic option for this challenging patient population.