Novel JAK1 inhibitor relieves symptoms in active RA

Use of the selective JAK1 inhibitor SHR0302 significantly improves the clinical signs and symptoms of patients with moderate-to-severe active rheumatoid arthritis (RA) who had shown poor response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), according to a study presented at EULAR 2024.

Such improvements persist throughout the year, and the use of this novel drug is also well tolerated, with no new safety signals and no deaths reported.

“This study suggests that SHR0302 might represent a novel treatment option for patients with RA,” said co-author Dr Jinjing Liu from the Peking Union Medical College Hospital in Beijing, China.

Liu and her team randomly assigned 566 patients with active RA to receive either placebo or SHR0302 4 or 8 mg, administered orally once daily for 24 weeks. They stratified patients by concomitant csDMARDs use at baseline (either methotrexate ≥15 mg/week or leflunomide 20 mg/day; methotrexate <15 mg/week or leflunomide <20 mg/day; or no usage of either methotrexate or leflunomide).

Demographics and disease characteristics at baseline did not significantly differ across the treatment arms. Of the participants, 524 (92.6 percent) completed the 24-week treatment, and 496 (87.6 percent) completed the 52-week treatment. [EULAR 2024, abstract OP0037]

Response rates

The American College of Rheumatology response criteria (ACR20) response rates at week 24 were substantially greater for patients treated with SHR0302 at doses of 4 mg (70.4 percent; p<0.0001) and 8 mg (75.1 percent; p<0.0001) than those on placebo (40.4 percent). Likewise, ACR50 and ACR70 response rates were significantly improved with the SHR0302 doses relative to placebo.

“The onset of action was rapid, with obviously more patients in both SHR0302 arms achieving ACR20 at week 2 compared to the placebo group,” Liu said.

At week 24, more patients achieved a DAS28-CRP of <2.6 and ≤3.2 in the SHR0302 4-mg (29.6 percent and 46.0 percent, respectively; p<0.0001) and 8-mg (39.2 percent and 57.1 percent; p<0.0001) arms than those in the placebo arm (4.8 percent and 15.4 percent).

Additionally, both SHR0302 doses resulted in markedly greater changes from baseline in HAG-DI scores (4 mg: least squares mean change [LSMC], ‒0.45 for 4 mg; p<0.0001; 8 mg: LSMC, ‒0.51; p<0.0001) at week 24 compared with the placebo group (LSMC, ‒0.21).

Patients receiving SHR0302 also showed numerically greater changes from baseline in the SF-36 score at week 24 (PCS: LSMC, 5.62 for 4 mg and 6.43 for 8 mg; MCS: LSMC, 2.85 for 4 mg and 4.04 for 8 mg; p<0.0001) than those receiving placebo (PCS: LSMC, 1.78; MCS: LSMC, ‒0.22).

“These trends in improvements were sustained over an additional 28 weeks,” Liu said.

Adverse events

In terms of safety, treatment-emergent adverse events (TEAEs) occurred in 81.5 percent of patients in the SHR0302 4-mg group, 90.5 percent of those in the SHR0302 8-mg group, and 79.3 percent of those in the placebo group. Infections were slightly more frequent in the SHR0302 arms than in the placebo arm (40.2 percent and 40.7 percent vs 34.0 percent).

“However, few cases of serious infection and systemic opportunistic infection were reported,” said Liu.

Furthermore, Liu and colleagues documented one newly diagnosed malignancy in the SHR0302 4-mg group, one thromboembolic event and one major cardiovascular event in the SHR0302 8-mg group, and two cases of liver function abnormality (one in each SHR0302 dose group). Fortunately, no deaths, tuberculosis cases, or gastrointestinal perforations occurred.

When asked regarding the incidence of herpes zoster (HZ), which is common a common problem with this type of drug, Liu said that there were two cases: one patient discontinued treatment due to HZ and another because of pain caused by HZ. “There were two of them, [but] still very few,” she noted.

In this study, patients who were initially treated with placebo were switched to SHR0302 4 mg for an additional 28 weeks, while those originally assigned to any of the SHR0302 doses continued with their initial dosage.

SHR0302 previously demonstrated its efficacy and safety in treating patients with active RA in a phase II trial (NCT03254966).