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Título

Efficacy and safety of upadacitinib as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from phase 3 U-ACCOMPLISH study

Introdução

Upadacitinib (UPA) is a selective and reversible Janus kinase inhibitor. U-ACCOMPLISH is one of two phase 3 induction trials that evaluated the safety and efficacy of UPA 45 mg once daily (QD) in adults with ulcerative colitis (UC).

Objetivo

To evaluate the safety and efficacy of UPA 45 mg QD in adults with UC.

Método

U-ACCOMPLISH was a multicentre, randomized, double-blind, placebo-controlled trial (NCT03653026) that enrolled patients (pts) with moderate-to-severe UC who had inadequate response, loss of response, or intolerance to 5-ASA, immunosuppressants, corticosteroids and/or biologics. Pts were randomized 2:1 to UPA 45 mg QD or placebo (PBO) for 8 weeks. At week 8, responders entered the maintenance phase and non-responders entered the extended treatment period to receive open-label UPA 45 mg QD for additional 8 weeks. The primary endpoint (clinical remission per adapted Mayo Score) and ranked secondary endpoints including symptomatic, endoscopic–histologic evaluations from the 8-week PBO-controlled period are reported here. Non-responder imputation incorporating multiple imputation for missing data due to COVID-19 are reported.

Resultados

522 pts were randomized (UPA, n=345; PBO, n=177); the ITT population included 341 pts in UPA and 174 pts in PBO group. Baseline demographics and disease characteristics were similar between groups; 50.7% and 51.1% were biologic inadequate responders in UPA and PBO groups, respectively. A significantly higher proportion of pts receiving UPA 45 mg QD (33.5%) vs. PBO (4.1%) achieved the primary endpoint (adjusted treatment difference: 29.0% [23.2, 34.7]; P<0.001). A significantly higher proportion of pts receiving UPA versus PBO also achieved all ranked secondary endpoints (all P<0.001). Serious adverse events were reported by 3.2% and 4.5% of pts in UPA and PBO groups, respectively. Similar rates of serious infection were observed in both groups (0.6%); 2 events each of H. zoster and opportunistic infection were reported in UPA group. No active TB, malignancy, adjudicated MACE, or deaths were reported in the study. One patient with VTE (DVT and PE) and 1 patient with GI perforation were reported in the PBO group.

Conclusão

In U-ACCOMPLISH, 8-week UPA 45 mg QD induction treatment led to statistically significant improvements in clinical, endoscopic, and combined endoscopic-histologic endpoints. The treatment was well tolerated, and the safety profile and AE prevalence was comparable with previous studies of UPA with no new safety signals identified.

Palavras-Chave

upadacitinib, ulcerative colitis, efficacy, safety

Área

Gastroenterologia - Intestino

Autores

Séverine Vermeire, Silvio Danese, Wen Zhou, Aileen Pangan, Susan Greenbloom, Geert D’Haens, Julian Panes, Pascal Juillerat, James O Lindsay, Edward V Loftus Jr, William J Sandborn, Walter Reinisch, Yuri Sanchez Gonzalez, Bidan Huang, Wangang Xie, John Liu, Michael A Weinreich, Remo Panaccione, Julio C N Carvalho