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Título

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

Introdução

An unmet therapeutic need remains in patients(pts) with ulcerative colitis (UC). U-ACHIEVE is one of two phase 3 induction trials evaluating the safety and efficacy of the selective JAK-1 inhibitor upadacitinib (UPA) 45 mg once daily (QD) in adults with UC.

Objetivo

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

Método

It was a multicentre, double-blind, placebo (PBO)-controlled trial (NCT02819635) that randomized pts with mod-to-sev active UC 2:1 to UPA 45 mg QD or PBO for 8 weeks.Randomization was stratified by biologic inadequate responder status, baseline corticosteroid use (yes or no), and baseline adapted Mayo Score (MS) (≤7 or >7).The primary endpoint was proportion of pts achieving clinical remission (per adapted MS) at wk 8. Ranked secondary endpoints included endoscopic improvement at wk 8, endoscopic remission at wk 8, clinical response per adapted MS at wk 8, clinical response per partial adapted MS at wk 2, and histologic-endoscopic mucosal improvement at wk 8. NRI incorporating multiple imputations for missing data due to COVID-19 are reported. Safety was assessed through wk 8.

Resultados

474 pts were randomized (UPA, n=319; PBO, n=155). Baseline characteristics were well balanced between groups. A significantly higher proportion of pts receiving UPA (26.1%) vs PBO (4.8%) achieved clinical remission at wk 8 (adjusted treatment difference [95% CI]: 21.6% [15.8, 27.4]; P<0.001). For all ranked secondary endpoints, UPA was superior to PBO (P<0.001). A significant difference vs PBO in clinical response favouring UPA was seen as early as wk 2 (60.1% vs 27.3%) and was sustained thereafter up to wk 8 (79.0% vs 41.6%). Serious AEs, severe AEs, and AEs leading to study drug discontinuation were higher in the PBO group. Acne, CPK elevation, and nasopharyngitis were the most common AEs with UPA and worsening of UC and anaemia with PBO. Incidence of serious infection was similar between UPA and PBO. Neutropenia and lymphopenia were reported more frequently with UPA vs PBO. No adjudicated GI perforation, MACE, or thrombotic events, and no active TB, malignancy, or deaths were reported.

Conclusão

In pts with mod-to-sev active UC, UPA 45 mg QD induction therapy was superior to PBO in inducing clinical remission/response, and endoscopic remission/response over 8 weeks; responses were significant and rapid. UPA 45 mg QD was well-tolerated; safety was comparable with the known safety profile of UPA, and no new safety signals were identified.

Palavras-Chave

upadacitinib, ulcerative colitis, efficacy, safety

Área

Gastroenterologia - Intestino

Autores

Silvio Danese, Séverine Vermeire, Wen Zhou, Aileen Pangan, Jesse Siffledeen, Xavier Hébuterne, Hiroshi Nakase, Peter D R Higgins, Min-Hu Chen, Yuri Sanchez Gonzalez, Bidan Huang, Wangang Xie, John Liu, Michael A Weinreich, Remo Panaccione, Julio C N Carvalho