P535 Effectiveness of upadacitinib in patients with Ulcerative Colitis: a real-life, multicenter, Italian report

Abstract

Abstract Background Upadacitinib (UPA) is an oral, selective JAK inhibitor, that has recently received approval in Italy for the treatment of Ulcerative colitis (UC). To our knowledge, only few data of real-life studies are available. The aim of our observational data collection is to report the first real-life experiences with UPA in UC in terms of effectiveness and safety. Methods These data come from four Italian IBD centers. Adult patients with a diagnosis of UC, who have been prescribed UPA for active disease, after failure of at least one anti-TNF therapy, were enrolled. After an induction period of 8 weeks with a 45 mg daily dosage, treatment efficacy were assessed using the partial Mayo score (pMS) and the fecal calprotectin levels (CP). Treatment-related adverse events were also recorded. Results Among 20 patients who started UPA, 12 have completed the induction and were therefore enrolled and evaluated before starting UPA and at the end of the 8 weeks induction period. 83% (10 patients) had previously failed two or more biological therapies, including tofacitinib (3 patients, 25%). 3 patients (25%) were tapering systemic corticosteroids and 3 patients (25%) were receiving topical steroids when they started UPA. In the pre-treatment evaluation, the mean pMs was 5,25 (SD 2,26) and the median CP was 1270 ug/g (411- 3152). At the end of induction (week 8), 10 patients (83%) achieved clinical remission and one patient showed clinical response with a decrease of 6 points of pMS. One patient underwent colectomy after 4 weeks of ineffective therapy. The mean pMS at week 8 was 0 (SD 0,92) (Fig. 1), with a median CP of 88 ug/g (5-4639). Reported adverse events, that however did not cause drug discontinuation, were one case of leukopenia and one case of acne. To the date of the last evaluation, all patients maintained the achieved results, with a mean follow-up period of 92 days. A further analysis excluding the physician global assessment from pMS has been performed, to obtain a sort of patient-reported outcome 2 (PRO-2): the results, in terms of percentage reduction of the scores, were in line with the presented data. Despite the limited number of patients who completed the induction (11), we observed statistical significance in the difference between pretreatment and post-induction values of all the measured variables (Tab. 1, Fig. 1). Conclusion With this first Italian report in a real-life setting, UPA showed promising effects in rapidly inducing clinical remission and in normalizing a sensitive marker of intestinal inflammation. Moreover, it seems to be well tolerated. Long-term real-life studies, including endoscopic and histologic evaluations, are needed to confirm efficacy and safety of UPA in maintaining stable remission in UC patients.