Efficacy and safety of iguratimod in patients with primary Sjögren’s syndrome: a multicentre randomised controlled trial

Objective This multicentre randomised controlled trial aimed to compare the efficacy and safety of iguratimod (IGU) and hydroxychloroquine (HCQ) in patients with active primary Sjögren’s syndrome (pSS). Methods Eligible pSS patients were randomised 1:1 to receive IGU (25 mg two times per day) or HCQ (0.2 g two times per day) for 24 weeks. The primary endpoint was the Sjögren’s Syndrome Responder Index-30 (SSRI-30) response rate at week 24. Secondary endpoints included the Sjögren’s Tool for Assessing Response (STAR), European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and biomarker changes. Results A total of 78 pSS patients were randomised (40 in HCQ group, 38 in IGU group) and 66 patients (35 in HCQ group, 31 in IGU group) completed the 24-week research. SSRI-30 response rate, the primary endpoint, was numerically higher in the IGU group (57.9% vs 40.0%, p=0.114), but with no statistical significance. However, IGU demonstrated significantly higher response rates for key secondary endpoints including STAR (39.5% vs 15.0%, p=0.015) and ESSDAI (21.1% vs 5.0%, p=0.034) response rate. IGU also showed superior IgG reduction (p=0.046). Adverse events were more frequent with IGU (60.6% vs 37.8%) but were mostly mild. Conclusion IGU monotherapy demonstrated significant improvements in composite, systemic and serologic outcomes compared with HCQ in active pSS and was well-tolerated. These findings establish IGU as a promising therapeutic option for pSS, particularly in the subset of patients with hyperglobulinaemia. Trial registration number NCT04981145 .