Journal Article

Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease

Boland, Brigid S., Liu, Jianzhong, Panaccione, Remo, D’Haens, Geert, Reinisch, Walter, Louis, Edouard, Chen, Minhu, Phillips, Charles, Panés, Julian, Lacerda, Ana P., Loftus, Edward V., Mohamed, Mohamed-Eslam F., Feng, Tian, Dubcenco, Elena, Nakase, Hiroshi, Colombel, Jean-Frederic, Geng, Ziqian, Peyrin-Biroulet, Laurent, Begun, Jakob

2023

Overview

Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn's disease. In two phase 3 induction trials (U-EXCEL and U-EXCEED), we randomly assigned patients with moderate-to-severe Crohn's disease to receive 45 mg of upadacitinib or placebo (2:1 ratio) once daily for 12 weeks. Patients who had a clinical response to upadacitinib induction therapy were randomly assigned in the U-ENDURE maintenance trial to receive 15 mg of upadacitinib, 30 mg of upadacitinib, or placebo (1:1:1 ratio) once daily for 52 weeks. The primary end points for induction (week 12) and maintenance (week 52) were clinical remission (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]) and endoscopic response (defined as a decrease in the Simple Endoscopic Score for Crohn's Disease [SES-CD; range, 0 to 56, with higher scores indicating more severe disease] of >50% from baseline of the induction trial [or for patients with an SES-CD of 4 at baseline, a decrease of ≥2 points from baseline]). A total of 526 patients underwent randomization in U-EXCEL, 495 in U-EXCEED, and 502 in U-ENDURE. A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P<0.001 for all comparisons). At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P<0.001 for all comparisons). Herpes zoster infections occurred more frequently in the 45-mg and 30-mg upadacitinib groups than in the respective placebo groups, and hepatic disorders and neutropenia were more frequent in the 30-mg upadacitinib group than in the other maintenance groups. Gastrointestinal perforations developed in 4 patients who received 45-mg upadacitinib and in 1 patient each who received 30-mg or 15-mg upadacitinib. Upadacitinib induction and maintenance treatment was superior to placebo in patients with moderate-to-severe Crohn's disease. (Funded by AbbVie; U-EXCEL, U-EXCEED, and U-ENDURE ClinicalTrials.gov numbers, NCT03345849, NCT03345836, and NCT03345823.).

• Publisher: Massachusetts Medical Society
• Subject: 4RA0KN46E0 (upadacitinib) / Abdomen / Allergy / Arthritis / Clinical trials / Crohn Disease - complications / Crohn Disease - drug therapy / Crohn Disease/complications/drug therapy / Crohn's disease / Endoscopy / FDA approval / Gastroenterology / Gastroenterology & hepatology / Gastroenterology General / Gastroentérologie & hépatologie / Herpes zoster / Herpes Zoster - chemically induced / Herpes Zoster - etiology / Herpes Zoster/chemically induced/etiology / Heterocyclic Compounds, 3-Ring / Heterocyclic Compounds, 3-Ring - administration & dosage / Heterocyclic Compounds, 3-Ring - adverse effects / Heterocyclic Compounds, 3-Ring - therapeutic use / Heterocyclic Compounds, 3-Ring/administration & dosage/adverse effects/therapeutic use / Human health sciences / Humans / Immunodeficiency / Immunology / Induction Chemotherapy - adverse effects / Induction Chemotherapy - methods / Induction Chemotherapy/adverse effects/methods / Induction therapy / Inflammatory Bowel Disease / Janus kinase / Janus Kinase Inhibitors / Janus Kinase Inhibitors - administration & dosage / Janus Kinase Inhibitors - adverse effects / Janus Kinase Inhibitors - therapeutic use / Janus Kinase Inhibitors/administration & dosage/adverse effects/therapeutic use / Laboratories / Maintenance Chemotherapy - adverse effects / Maintenance Chemotherapy - methods / Maintenance Chemotherapy/adverse effects/methods / Neutropenia / Neutropenia - chemically induced / Neutropenia - etiology / Neutropenia/chemically induced/etiology / Pain / Patients / Placebos / Remission / Remission (Medicine) / Sciences de la santé humaine / Statistical analysis