P383 Ustekinumab as an opportunity for refractory Ulcerative Colitis patients

Abstract

Background There are limited data in real-life of ustekinumab (USK) used in ulcerative colitis (UC). The aim of this study was to assess the effectiveness and safety in clinical practice of USK in UC in the medium and long-term. Methods Observational study in UC patients who received USK at the recommended dose based on weight ~6 mg/kg IV week, 0.90 mg SC week, 8 and maintenance, 90 mg SC every, 8 or, 12 weeks and with, 1 year of follow-up. The partial Mayo score (PMS) was used to assess clinical remission (PMS≤, 2). The PMS, C-reactive protein (CRP) and faecal calprotectin (FC) values ​​were recorded at baseline and after, 8, 16, 24 and, 52 weeks. Dose adjustment was performed by the measure of UST trough levels by ELISA, when patient lost clinical and/or biochemical response and the levels were low (<1.3 µg/ml). Demographic, clinical, biochemical and endoscopic data, previous treatments, adverse events (AEs), surgeries and hospitalizations, were documented. Results Twenty-three patients with UC were analysed. (Table, 1). All patients had received previous biological treatment:, 52% ≥2 anti-TNF, 65% vedolizumab and, 30% JAK inhibitors. Treatment discontinuation occurred in, 3 patients (13%). The persistence was, 83% and, 79% at, 6 and, 12 months (Figure, 1). During follow-up, 12 patients (52%) maintained standard dose of USK. Dose adjustment was performed in, 13 patients (56%):, 3 (13%) required intravenous UST reinduction and, 10 (43%) required dose escalation (8 by shortening the interval between doses and, 2 by switching to intravenous USK administration). Clinical remission was reached in, 61%, 58%, 56%, 79% of the patients after, 8, 16, 24, 52 weeks, respectively. Normal CRP (<5mg/L) and FC (<150 µg/g) levels were achieved in, 76%, 93% and, 80% and in, 35%, 31% and, 40% of patients after, 8, 24, 52 weeks, respectively. Five of, 6 patients who had endoscopy before and after treatment showed endoscopic Mayo subscore ≤1. There were, 2 AEs, 1 hospitalization, and, 1 colectomy during follow-up. Conclusion This study demonstrates the safety as well as the clinical, biological and endoscopic effectiveness of USK adjusted by levels in real life in a highly refractory UC cohort.

Meta‐analysis: Real‐world effectiveness and safety of ustekinumab in patients with ulcerative colitis

“…In all, 11 studies [6][7][8][9]16,19,20,[22][23][24]26 Between-study heterogeneity was considerable at week 8 (I 2 = 87%) and month 12 (I 2 = 82%), might be not important at weeks 12-16 (I 2 = 26%), and was substantial at month 6 (I 2 = 65%) (Figure 1).…”

“…Of the 254 citations identified, 19 studies including 3786 patients with UC were eligible for inclusion in this systematic review (Table S2). [5][6][7][8][9][15][16][17][18][19][20][21][22][23][24][25][26][27][28] In all, 13 studies were reported as full-text articles, and 6 were conference proceedings. According to JBI criteria for quality assessment, 14 studies showed low risk of bias, and 5 articles showed moderate risk (Table S3).…”

“…Nine studies [5][6][7][8]18,20,23,24 assessed endoscopic improvement in 236 patients (Figure 3). At weeks 12-16, the pooled rate of endoscopic improvement was 29.9% (95% CI: 21.1-38.7) (91 patients; 2 studies: 6, 18).…”

“…Dose escalation rates were reported in 10 studies [7][8][9][15][16][17]20,21,24,27 (n = 629). During follow-up, dose escalation was required in 28.4% of patients (95% CI: 14.7-44.3; range 0%-63.1%) (Figure S3A).…”

“…Across nine studies including 634 patients, 5,9,[18][19][20]24,26,7 the pooled rate of persistence with ustekinumab at month 12 was 73.3% (95% CI: 64.6-82) (Figure S4B). Between-study heterogeneity at this timepoint was substantial (I 2 = 85%, Cochrane's Q test p = 0.001).…”