Ivarmacitinib curbs rheumatoid arthritis symptoms, improves function through 52 weeks
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Key takeaways:
- Ivarmacitinib 4 mg and 8 mg showed benefits through a year in patients with moderate to severe RA and inadequate response to csDMARDs.
- Those on 8 mg had more treatment-emergent adverse events.
A once-daily dose of ivarmacitinib reduced disease activity and improved function among patients with rheumatoid arthritis through 52 weeks, according to phase 3 trial results published in Annals of the Rheumatic Diseases.
“Ivarmacitinib (formerly SHR0302), an orally administered, highly selective JAK1 inhibitor, exhibits potency and selectivity for JAK1 that is over 10-fold for JAK2, 77-fold for JAK3 and 420-fold for TYK2,” Jinjing Liu, of the department of rheumatology and clinical immunology at Peking Union Medical College Hospital, in Beijing, and colleagues wrote.
“A phase 2 clinical trial (NCT03254966) in Chinese patients with moderate-to-severe active RA, either treatment-naïve or with an inadequate response to csDMARDs, demonstrated that ivarmacitinib had a rapid onset of action, leading to statistically significant improvements in American College of Rheumatology (ACR) 20 response rates at 12 weeks ... with a safety profile similar to other JAK inhibitors,” they added.
To further investigate the safety and efficacy of ivarmacitinib (Jiangsu Hengrui Medicine) in patients with RA who had an inadequate response to conventional synthetic DMARDs, Liu and colleagues conducted a phase 3 trial across 59 sites in China.
In the double-blind trial, adults with active, moderate to severe RA were randomly assigned in a 1:1:1 ratio to receive once-daily doses of oral ivarmacitinib, either 4 mg or 8 mg (n = 189 for both), or placebo (n = 188) for 24 weeks. Placebo-treated patients were then switched to 4 mg ivarmacitinib for a 28-week extension while ivarmacitinib-treated patients continued their regimen and remained blinded.
To be eligible for inclusion, patients had to either be receiving up to two conventional synthetic DMARDs or have previously failed, or were unable to tolerate, at least one conventional synthetic DMARD. For the primary endpoint, the researchers examined the proportion of patients who achieved at least 20% improvement in the American College of Rheumatology response criteria at week 24.
According to the researchers, both ivarmacitinib treatment groups demonstrated statistically significant ACR responses that separated from placebo in the early weeks of the trial, and were maintained throughout. ACR20 response was significantly more frequent among those treated with ivarmacitinib 4 mg (70.4%) or 8 mg (75.1%) vs. the placebo group (40.4%), with both comparisons showing P < .0001.
Ivarmacitinib also led to improvements in DAS28 joint count with C-reactive protein. At week 24, the proportions of patients with scores at or below 3.2, or below 2.6, were numerically greater in the ivarmacitinib 4 mg group (46% and 29.6%, respectively) and 8 mg group (57.1% and 39.2%, respectively), compared with the placebo group (15.4% and 4.8%, respectively).
Meanwhile, placebo-treated patients who switched to 4 mg ivarmacitinib also demonstrated numerical gains across a range of efficacy outcomes that were sustained to week 52.
Regarding safety, the placebo-controlled period saw treatment-emergent adverse events reported among 81.5% of those on ivarmacitinib 4 mg and in 90.5% of those receiving 8 mg, compared with 79.3% of those in the placebo group. The higher rate in the 8 mg group suggests “a possible dose-response relationship,” the researchers wrote, adding that the most common treatment-emergent adverse events with ivarmacitinib were upper respiratory tract infections (4 mg: 21.7%; 8 mg: 22.8%) and hyperlipidemia (4 mg: 15.3%; 8 mg: 12.2%).
“Ivarmacitinib at doses of 4 or 8 mg once daily was superior to placebo in reducing RA signs and symptoms, decreasing disease activity and improving physical function over a 24-week treatment period in patients with active RA who had an inadequate response to csDMARDs,” Liu and colleagues wrote. “These improvements were sustained throughout the study period. Overall, both doses of ivarmacitinib demonstrated a favorable benefit-to-risk profile similar to other approved JAK inhibitors.”
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