Details

Autor(en) / Beteiligte

• Chen, Baili
• Zhong, Jie
• Li, Xiuling
• Pan, Feng
• Ding, Yijuan
• Zhang, Yan
• Chen, Hong
• Liu, Fei
• Zhang, Zhenyu
• Zhang, Ling
• Drozda, Rafal
• Oliinyk, Oleksandr
• Goh, Aik Han
• Chen, Xiang
• Sun, Xiang
• Rubin, David T.
• Sandborn, William J.
• Chen, Minhu

Titel

Efficacy and Safety of Ivarmacitinib in Patients With Moderate-to-Severe, Active, Ulcerative Colitis: A Phase II Study

Ist Teil von

• Gastroenterology (New York, N.Y. 1943), 2022-12, Vol.163 (6), p.1555-1568

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. 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 1:1:1:1 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. 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. 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 Oral ivarmacitinib was found to be a safe and effective therapy for adult patients with moderate-to-severe, active ulcerative colitis, and holds promise as a new treatment option for this condition.