Efficacy and Safety of Ivarmacitinib in Patients With Moderate-to-Severe, Active, Ulcerative Colitis: A Phase II Study.
Gastroenterology
; 163(6): 1555-1568, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-35963369
ABSTRACT
BACKGROUND & AIMS:
Current therapies for ulcerative colitis (UC) fail to achieve satisfactory disease control. Selective inhibition of Janus kinase (JAK) type 1 may improve clinical outcomes in patients with UC while avoiding the side effects associated with pan-JAK inhibition. The safety and efficacy of the selective JAK1 inhibitor ivarmacitinib (formerly SHR0302) were evaluated in patients with moderate-to-severe, active UC.METHODS:
AMBER2 was a double-blind, placebo-controlled, phase II trial conducted at 63 clinical centers in China, the United States, and Europe. Patients (N = 164) were randomized 1111 to receive oral ivarmacitinib 8 mg once daily (QD), 4 mg twice daily (BID), or 4 mg QD, or placebo for 8 weeks, followed by an 8-week extension period. The primary endpoint was clinical response rate at week 8. Hochberg's procedure was used to control the study-wise type 1 error at alpha=0.1.RESULTS:
A total of 146 (89.0%) patients completed 8 weeks of treatment. Week 8 clinical response rates were significantly higher in the 8 mg QD (46.3%; P = .066), 4 mg BID (46.3%; P = .059), and 4 mg QD (43.9%; P = .095) groups vs placebo (26.8%). Week 8 rates of clinical remission were 22.0% (P = .020), 24.4% (P = .013), and 24.4% (P = .011) in the 3 ivarmacitinib treatment groups, respectively, vs 4.9% for placebo. During the initial 8-week period, treatment-emergent adverse events occurred in 43.9% to 48.8% of ivarmacitinib-treated patients and in 39.0% of the placebo group, and were predominantly mild. There were no deaths, or major adverse cardiovascular or thromboembolic events.CONCLUSION:
Ivarmacitinib demonstrated clinical efficacy and was well tolerated in patients with moderate-to-severe, active, UC. Ivarmacitinib represents a promising new treatment for moderate-to-severe UC. CLINICALTRIALS gov number, NCT03675477.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colite Ulcerativa
/
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
/
Inibidores de Janus Quinases
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Gastroenterology
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China