Colon to Rectum
Gastroenterology. 2022;163(6):1555–68
Efficacy and safety of ivarmacitinib in patients with moderate-to-severe, active, ulcerative colitis: A phase 2 study
Background and 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 2 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 (q.d.), 4 mg twice daily (b.i.d.), or 4 mg q.d., or placebo for 8 weeks, followed by an 8-week extension period. The primary end point 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 patients (89.0%) completed 8 weeks of treatment. Week 8 clinical response rates were significantly higher in the 8 mg q.d. (46.3%; p = 0.066), 4 mg b.i.d. (46.3%; p = 0.059), and 4 mg q.d. (43.9%; p = 0.095) groups versus placebo (26.8%). Week 8 rates of clinical remission were 22.0% (p = 0.020), 24.4% (p = 0.013), and 24.4% (p = 0.011) in the 3 ivarmacitinib treatment groups, respectively, versus 4.9% for placebo. During the initial 8-week period, treatment-emergent adverse events occurred in 43.9–48.8% 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 ulcerative colitis (UC). Ivarmacitinib represents a promising new treatment for moderate-to-severe UC.