- Indian Rheumatology association
Ankit Jain MD, DM Clinical Immunology
Consultant, Immunology & Rheumatology Clinic, Meerut, Uttar Pradesh
Study in Focus 1: Ivarmacitinib, a selective Janus kinase 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis(RA) and inadequate response to conventional synthetic DMARDs: results from a phase III randomised clinical trial (1)
Over the last decade, numerous JAK inhibitors have been approved for treatment of RA. In this phase III randomized, double-blind, placebo-controlled trial, the efficacy and safety of ivarmacitinib, a novel selective JAK1 inhibitor, in patients with moderate-to-severe rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs (csDMARDs) was evaluated. Conducted at 59 sites in China, 566 patients were randomized to receive ivarmacitinib 4 mg, 8 mg, or placebo once daily for 24 weeks, with placebo patients switching to ivarmacitinib 4 mg for an additional 28 weeks. At 24 weeks, ACR20 response rates were significantly higher with ivarmacitinib 4 mg (70.4%) and 8 mg (75.1%) compared to placebo (40.4%, p<0.0001). Both doses also showed superior ACR50/70 responses, reduced disease activity (DAS28 (CRP)), and improved physical function (HAQ-DI) and quality of life (SF-36 PCS/MCS), with benefits sustained through 52 weeks. Safety profiles were consistent with other JAK inhibitors, with treatment-emergent adverse events (TEAEs) reported in 81.5% (4 mg), 90.5% (8 mg), and 79.3% (placebo), primarily upper respiratory tract infections and hyperlipidemia. Serious adverse events were infrequent, and no new safety signals emerged. Ivarmacitinib demonstrated robust efficacy and a manageable safety profile, suggesting it may serve as an effective treatment option for RA patients who do not respond adequately to csDMARDs.
Study in Focus 2: Evaluation and prediction of relapse risk in stable systemic lupus erythematosus patients after glucocorticoid withdrawal (PRESS): an open-label, multi- centre, non-inferiority, randomised controlled study in China (2)
Duration of steroid therapy and the timing of its withdrawal has been a topic of debate since long. The PRESS study, an open-label, multicenter, non-inferiority randomized controlled trial conducted in China, evaluated relapse risk in stable SLE patients after GC withdrawal with or without hydroxychloroquine (HCQ) maintenance. A total of 333 participants with sustained clinically inactive SLE were randomized into three groups: drug-free (GC and HCQ withdrawal), HCQ maintenance (GC withdrawal but continued HCQ), and dual maintenance (both GC and HCQ continued). At 33 weeks, relapse rates were 26.1% (drug-free), 11.2% (HCQ), and 4.7% (dual maintenance). While HCQ maintenance showed non-inferiority to dual maintenance (relapse difference 6.5%, p=0.034), drug-free withdrawal did not (relapse difference 21.4%, p=0.238). HCQ significantly reduced relapse risk compared to drug-free withdrawal (p=0.006).
Mild/moderate relapses were more common than severe ones, with mucocutaneous lesions and nephritis prevalent in the drug-free group. Logistic regression identified higher GC doses at baseline and early disease onset as potential risk factors for relapse. No significant differences in severe relapse rates or adverse events were noted among groups, except one case of myocardial infarction in the HCQ group. The study concluded that GC withdrawal is feasible for stable SLE patients, particularly when HCQ is maintained, but a drug-free approach poses a higher relapse risk. HCQ monotherapy emerged as a viable GC substitute for long-term maintenance in SLE, though careful patient selection and further validation are essential.
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