16 hours ago
JAK1 Inhibitor Shows Promise for Ankylosing Spondylitis
TOPLINE:
Ivarmacitinib, a highly selective Janus kinase 1 (JAK1) inhibitor, tamed ankylosing spondylitis with sustained efficacy through 24 weeks in a phase 2/3 trial.
METHODOLOGY:
A phase 2/3 trial in China evaluated the efficacy and safety of ivarmacitinib in 504 adults with active ankylosing spondylitis who did not benefit from nonsteroidal anti-inflammatory drugs (NSAIDs).
In phase 2, patients were randomly assigned to receive ivarmacitinib (2 mg, 4 mg, or 8 mg) or placebo once daily for 12 weeks; 4 mg was selected as the recommended dose based on an interim analysis.
In phase 3, 373 patients (mean age, 33.8 years; 79.6% men) were randomly assigned to receive 4 mg ivarmacitinib (n = 187) or placebo (n = 186) once daily for 12 weeks, after which all patients got ivarmacitinib for 12 weeks.
The primary endpoint in both phases was the proportion of patients achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 response at week 12.
TAKEAWAY:
At week 12, 48.7% of patients who received 4 mg ivarmacitinib achieved an ASAS20 response compared with 29% of those who received placebo (P = .0001).
More patients on 4 mg ivarmacitinib vs placebo achieved an ASAS40 response (32.1% vs 18.3%; P = .0011) and an ASAS5/6 response (42.8% vs 15.6%; P < .0001) at week 12, with efficacy sustained at week 24.
After 12 weeks of treatment, patients receiving 4 mg ivarmacitinib had greater improvements in disease symptoms, physical function, spinal mobility, and quality of life.
During the first 12-week period, treatment-emergent adverse events occurred in 79.7% of patients in the ivarmacitinib group and 65.6% in the placebo group but caused few treatment discontinuations.
IN PRACTICE:
'Ivarmacitinib 4 mg once daily provided rapid, sustained, and clinically meaningful improvements in disease activity, signs and symptoms, function, and MRI-detected inflammation in patients with active AS [ankylosing spondylitis] who had an inadequate response to NSAIDs, with a manageable safety profile,' the authors wrote.
SOURCE:
This study was led by Xu Liu, MD, and Liling Xu, MD, of Peking University People's Hospital in Beijing, China. It was published online on June 12, 2025, in Arthritis & Rheumatology.
LIMITATIONS:
The 24-week efficacy of ivarmacitinib may not reflect long-term outcomes. The absence of an active comparator limited the comparison of ivarmacitinib with other disease-modifying antirheumatic drugs used for active ankylosing spondylitis. These findings in Chinese patients with radiographic axial spondyloarthritis may not be generalizable to other populations.
DISCLOSURES:
Jiangsu Hengrui Pharmaceuticals Co. Ltd. sponsored and designed the trial. Two authors reported being employees of the sponsor company while the study was conducted.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
