New JAK1 inhibitor outperforms placebo in active RA

The primary endpoint of American College of Rheumatology (ACR)20 was met by a significantly higher rate of patients with rheumatoid arthritis (RA) on the JAK1 inhibitor SHR0302 than on placebo. The agent also demonstrated superiority in more stringent secondary outcomes.

“SHR0302 is an orally administered, highly selective inhibitor of JAK1. The selectivity of SHR0302 for JAK1 is 9 times greater than that for JAK2,” described Dr Jinjing Liu (Peking Union Medical College Hospital, China) [1]. Due to encouraging results in phase 2 (NCT03254966), the compound advanced to a multicentre phase 3 trial (NCT04333771) including 566 adults with moderate-to-severe active RA [1]. Participants with previous inadequate responses to conventional synthetic DMARDs were randomised 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 51 years, 55.6–62.8% of participants in ACR functional class 2, a mean C-reactive protein level between 15.5 and 19.4 mg/L, and a mean swollen joint count ranging from 11.9–12.9.

Both SHR0302 groups reached the primary endpoint with significantly more participants achieving ACR20 than placebo: 70.4% on 4 mg (P<0.0001) and 75.1% on 8 mg (P<0.0001) compared with 40.4% on placebo. The ACR50 responses followed a similar pattern with 46.0% (P<0.0001), 57.1% (P<0.0001), and 15.4%, respectively. On the higher dose, just under a third of the participants also attained ACR70.

“These improvements were sustained throughout the 52-week treatment, and the placebo group which switched to SHR0302 4 mg also demonstrated favourable outcomes,” Dr Liu pointed out. She added that various patient-reported measures demonstrated significant ameliorations too.

Safety evaluations up to week 24 found incidences of adverse events in 81.5% (4 mg), 90.5% (8 mg), and 79.3% (placebo) of the participants. The most common adverse events were respiratory tract infections and hyperlipidaemia on SHR0302, besides respiratory tract infections and anaemia on placebo. All in all, Dr Liu regarded SHR0302 as generally well tolerated with a manageable safety profile.

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

1. Liu J, et al. A multicentre, randomised, placebo-controlled, double-blind, phase 3 study of SHR0302, a selective Janus kinase 1 inhibitor, in patients with active rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs. OP0037, EULAR 2024 Congress, 12–15 June, Vienna, Austria.

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Posted on 29 July 2024