P716 Efficacy and safety of upadacitinib during induction in Crohn’s disease: Real-world experience

Abstract

Abstract Background Upadacitinib is a selective JAK1 inhibitor that has recently been approved for treatment of moderate-severe Crohn’s disease, with Phase III clinical trials showing positive efficacy and safety profiles. Our aim was to evaluate the real-world experience of upadacitinib in a refractory cohort of Canadian patients with Crohn’s disease. Methods This was a two-centre retrospective study looking at 12-week induction data for patients with active Crohn’s disease from McGill University Health Centre and Hamilton Health Sciences. The primary outcome was clinical remission at 12 weeks, with secondary outcomes including clinical response, biochemical remission, and biochemical response. Clinical remission was defined as a Harvey-Bradshaw index (HBI) < 5. Clinical response was defined as an HBI reduction of ≥ 3. Biochemical remission was defined as a c-reactive protein (CRP) < 5 mg/L and/or fecal calprotectin (FCP) < 250 μg/g. Biochemical response was defined as a reduction of CRP or fecal calprotectin by 50% from baseline. These parameters were all evaluated at 8 and 12 weeks. Adverse events were summarized for patients who had follow up data available and included in the efficacy analysis. Results There were 28 patients who were treated in total, all of which had multiple biologic treatment failures. Baseline median age was 37, median HBI was 9, median CRP was 9.41 mg/L, and median FCP was 580 μg/g. The median disease duration was 13.5 years. Four patients discontinued upadacitinib due to no response or side effects. For all available data including patients who discontinued upadacitinib, clinical remission was achieved at 12 weeks in eight patients (8/11, 72.7%). Clinical response was achieved in eight patients (8/11, 72.7%), biochemical remission was achieved in four patients (4/11, 36.4%), and biochemical response was achieved in six patients (6/11, 54.6%). Of those that were initially on steroids (n=5), four patients (4/5, 80.0%) were able to wean off steroids and achieved a steroid-free clinical or biochemical response at 12 weeks. Of those who had previously been on off-label tofacitinib (n=5), clinical follow-up data was available for three patients at the end of the 12-week induction period. Two patients achieved clinical remission (2/3, 66.7%) and three patients had a clinical response (3/3, 100%). Among 13 patients with follow-up data, adverse events were observed in three patients (3/13, 23.1%), with two having non-serious infections (2/13, 15.4%) and one having fevers of unknown origin (1/13, 7.69%). Conclusion This real-world multicentre Canadian induction study shows favourable efficacy and tolerability of upadacitinib in refractory active Crohn’s disease.