New JAK1 Inhibitor Outperformed Placebo for Patients With Active Rheumatoid Arthritis

Jul 10, 2024

Photo Credit: Toa55

The highly selective JAK1 inhibitor SHR0302 achieved an American College of Rheumatology (ACR) 20 response on two tested doses.

SHR0302 demonstrated positive efficacy results with significantly higher proportions of patients with rheumatoid arthritis (RA), achieving an American College of Rheumatology (ACR) 20 response on both tested doses. The secondary endpoint rates of ACR50 and ACR70 also favored SHR0302.

Due to encouraging results in phase 2 (NCT03254966), the highly selective JAK1 inhibitor SHR0302 advanced to a multicenter phase 3 trial (NCT04333771), including 566 adults with moderate-to-severe active RA. Participants with previous inadequate responses to conventional synthetic disease-modifying antirheumatic drugs (DMARD) were randomized to either placebo or SHR0302 at doses of 4 mg or 8 mg daily. After the core phase of 24 weeks, the rate of participants achieving ACR20 was evaluated as the primary endpoint. In an extension period up to week 52, participants on placebo were switched to 4 mg of SHR0302, while the other groups continued their preceding medication.

Baseline values showed a mean age of around 50 years, between 55.6% and 62.8% of participants in ACR functional class 2, a mean CRP between 15.5 and 19.4 mg/L, and a mean swollen joint count of 66 joints ranging from 11.9 to 12.9. Jinjing Liu, MD, presented the results.

Both SHR0302 groups reached the primary endpoint, with significantly more participants achieving ACR20 than placebo: 70.4% on 4 mg (P<0.001), 75.1% on 8 mg (P<0.001) compared with 40.4% on placebo. The ACR50 responses followed a similar pattern with 46.0% (P<0.001), 57.1% (P<0.001), and 15.4%, respectively. On the higher dose, just under one-third of participants also attained ACR70. “The efficacy of SHR0302 was sustained throughout the extended 28-week treatment period,” Dr Liu pointed out.

Safety evaluations up to week 24 found adverse events in 81.5% (4 mg), 90.5% (8 mg), and 79.3% (placebo) of the participants. Dr Liu regarded SHR0302 as generally well tolerated with a manageable safety profile.

“This study provided evidence that SHR0302 might present a novel treatment option for patients with RA,” Dr. Liu concluded.