P723 Upadacitinib in Crohn’s disease: Real world experience from an early access program in Greece

Abstract

Abstract Background Upadacitinib is a novel selective Janus kinase 1 inhibitor, recently approved for the management of Crohn’s disease (CD) by Food and Drug Administration. In Greece, upadacitinib is available through an early access program for refractory patients who have exhausted their therapeutic options. Our goal was to describe our real practice experience. Methods This is a multicenter retrospective cohort study of adult patients with moderate to severe CD, who received upadacitinib. The primary endpoint was clinical response, defined by a reduction ≥3 in Harvey-Bradshaw index (HBI). Clinical remission was defined as HBI ≤4. Secondary endpoints included endoscopic and biochemical improvement based on physician’s assessment and CRP measurement, respectively. Outcomes were assessed at 12 weeks and at patient’s latest follow up. All patients received 45mg upadacitinib for 3 months and then 30mg for another 3 months, whereas the maintenance dose (30mg or 15mg) was based on the patient’s response. We also evaluated short -term safety. Results A total of 22 CD patients (12 female) received upadacitinib and were included in the analysis. Mean age 42.2 years (24-63). Five patients were active smokers. Mean treatment duration was 5.4 months (1-20). Two patients have not yet reached 12 weeks of treatment and were excluded from the efficacy analysis. Ten patients (45.4%) had ileocolonic Crohn’s, seven (31.8%) ileal disease and five (22.7%) Crohn’s colitis. Four patients had perianal disease and seven patients Crohn’s related surgery (5 ileocecal resection, 2 seton placement). Four patients had active extraintestinal manifestations: Three inflammatory arthritis and one atopic dermatitis. The majority of patients (15/20) had failed ≥ 3 biologics. All of them failed treatment with anti-TNF and 15 (75%) with ustekinumab. Six patients have just completed the induction period of 12 weeks, ten are on 30mg upadacitinib and four on 15mg. At 12 weeks, 18 patients achieved clinical response (90%). CRP was normal for 15/20 (75%) patients at 12 weeks. At last follow-up (mean 5.9 months, 3-20), all patients were in clinical remission. Endoscopy was available for six patients and improvement was documented for all of them. Adverse events occurred in 3 patients (15.7%): An episode of abdominal pain, a skin infection and a case of neutropenia. All adverse events resolved without discontinuing treatment. Conclusion In a small cohort of medically resistant Crohn’s patients, the short- term clinical efficacy of upadacitinib was high. No serious safety issues were recorded.