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Oral ivarmacitinib may be safe and efficacious for adult patients with moderate to severe, active ulcerative colitis (UC), according to a study in Gastroenterology.
The phase 2 randomized, double-blind, placebo-controlled, AMBER2 trial (ClinicalTrials.gov Identifier: NCT03675477) evaluated the efficacy and safety of oral ivarmacitinib, a selective JAK1 inhibitor, in adult patients with moderate to severe, active UC in 63 international centers from April 27, 2019, to February 3, 2021.
The participants were randomly assigned to receive ivarmacitinib 8 mg once daily, 4 mg twice daily, 4 mg once daily, or placebo orally for 8 weeks. After completion of the treatment phase, the patients had the option of participating in a blinded, active-treatment (ivarmacitinib 8 mg once daily, 4 mg twice daily, or 4 mg once daily), 8-week extension phase. The patients were followed until 2 weeks after the end of the extension phase.
Eligible participants were aged 18 to 75 years with active UC for at least 3 months and had a 9-point modified Mayo score (excluding the Physician Global Assessment subscore) of 5 to 9 points and an endoscopic subscore of 2 to 3. The primary endpoint was the rate of clinical response at week 8.
Researchers screened 296 patients but included a total of 164 patients. Of those, 82.3% completed the 16-week treatment period and 81.1% completed the entire 18-week period. The participants had a median age of 40.5 years, 61.0% were men, and 62.8% were Asian. A majority (89.6%) had a baseline total Mayo score of 10 or lower.
The full analysis set included all 164 participants. The unadjusted clinical response rates for the 8-mg once-daily, 4-mg twice-daily, 4-mg once-daily, and placebo groups at week 8 were 46.3%, 46.3%, 43.9%, and 26.8%, respectively.
The group differences for the 8-mg once-daily, 4-mg twice-daily, and 4-mg once-daily groups were 19.8% (90% CI, 2.8%-36.7%; P =.066), 20.1% (90% CI, 3.3%-37.0%; P =.059), and 17.7% (90% CI, 0.8%-34.5%; P =.095), respectively.
The ivarmacitinib groups had a higher percentage of participants who had clinical remission at week 8 according to the Mayo score: 22.0% for the 8-mg once-daily group (P =.020), 24.4% for the 4-mg twice-daily group (P =.013), and 24.4% for the 4-mg once-daily group (P =.011), compared with 4.9% for the placebo group.
Endoscopic improvement was achieved at week 8 by 26.8% of patients in the 8-mg once-daily group, 29.3% in the 4-mg twice-daily group, 36.6% in the 4-mg once-daily, and 14.6% in the placebo group. Endoscopic remission was achieved by 9.8% of patients in the 8-mg once-daily group, 14.6% in the 4-mg twice-daily group, 12.2% in the 4-mg once-daily group, and 4.9% in the placebo group.
Patients (45.1%) reported treatment-emergent adverse events (TEAEs) in the 8-week treatment period: 43.9% of patients in the 8-mg once-daily group, 48.8% in the 4-mg twice-daily group, 48.8% in the 4-mg once-daily group, and 39.0% in the placebo group. The most common TEAEs were anemia (4.9%) and worsened UC (4.9%). No major cardiovascular events, thromboembolic events, or deaths occurred.
Study limitations include the small sample of patients and short treatment duration. Also, the sample size was calculated according to the primary endpoint and may not be powered to detect statistically significant changes in the secondary endpoints.
“The phase II data presented here support the further clinical development of ivarmacitinib in a phase III trial with a larger patient population, toward addressing a substantial unmet need for a safe and effective therapy in patients with moderate-to-severe, active UC,” the study authors wrote.
Disclosure: This research was supported by Reistone Biopharma Co., Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Reference
Chen B, Zhong J, Li X, et al. Efficacy and safety of ivarmacitinib in patients with moderate-to-severe, active, ulcerative colitis: a phase II study. Gastroenterology. Published online August 10, 2022. doi:10.1053/j.gastro.2022.08.00
