P706 Tofacitinib in Moderate to Severe Ulcerative Colitis patients naïve to biological therapy: A prospective real world analysis of efficacy and safety

Abstract

Background Tofacitinib is an oral non-selective Janus Kinase inhibitor approved for Ulcerative colitis (UC) after the failure of biological therapy. Tofacitinib as first line therapy in biologic naive patients has not been evaluated. Methods We conducted a prospective study to assess the safety and efficacy of Tofacitinib as first line therapy in biologic naive moderate to severe UC. Tofacitinib was given at a dose of 10mg BD for 8 weeks followed by de-escalation to 5mg BD maintenance in responders. Dose escalation was done for relapses. Demographics, disease characteristics, concomitant medication, adverse events, severity and time to relapse were recorded. Clinical response and remission (defined as partial Mayo score: PMS decrease ≥2 and PMS ≤1 respectively) were measured at 4 weeks, 8 weeks, 24 weeks and 52 weeks. Endoscopic response (UCEIS score decrease ≥2) and remission (UCEIS 0-1) were assessed at 1 year. Time to event analysis was done to evaluate the cumulative rate of clinical response. Results 176 patients (136 biologic naive, 58% male; median age 40y [IQR:31-48y]) were included. Median baseline PMS and UCEIS score were 5 (IQR: 5-7 and 4-6 respectively) (Table 1). Of the biologic naïve cohort, clinical response was achieved in 68.4% and 79.4% at 4 and 8 weeks respectively. Clinical remission was achieved in 45.6%(4-weeks) and 55% (8-weeks). Maintenance of remission was seen in 44.1% and 32.4% in 24 and 52 weeks respectively (Fig1A). There was a significant reduction in PMS from baseline to end of 8-weeks (p<0.001) (Fig 1B). Corticosteroid-free clinical remission was achieved in 64.8% at 24-weeks. 106 patients (77.9%) maintained response till last follow-up. 11 relapsed after dose de-escalation (median time of 5m [range 3-22m]. 7/11 responded to dose escalation to 10mg. Endoscopic response was noted in 62.5% and remission in 33.9% with significant reduction in UCEIS from baseline to 52-weeks(p<0.001) (Fig 1B). Severe and minor adverse events were noted in 4 and 3 patients respectively (Table 1). Overall 1/3 of patients discontinued therapy at 24-weeks (14%) and 52 weeks (10%). No significant difference in proportion of clinical or endoscopic remission was observed between the biologic naïve and those with history of prior biologic usage (n=31, median time from withdrawal of biologics to Tofacitnib initiation=9 months). Conclusion Tofacitinib was effective in induction of clinical remission in more than half of biologic naive, moderate to severe UC . Three-fourth of these patients continued to be in remission at one year with few serious adverse events. Tofacitinib can be considered as upfront oral therapy after failure of conventional management.