Primary Sjögren’s syndrome (pSS) remains an area of major unmet need, with no approved disease-modifying therapies and only modest benefit seen with commonly used agents such as hydroxychloroquine (HCQ). Against this background, new data from a multicentre randomised controlled trial published in Rheumatic and Musculoskeletal Diseases Open suggest that iguratimod (IGU), an immunomodulatory drug already in use for rheumatoid arthritis, may offer a clinically relevant alternative for patients with active disease. Although evidence for IGU in pSS has so far been limited, this study provides the strongest support to date for its potential role in modifying disease activity.
The trial enrolled 78 patients with active primary Sjögren’s syndrome and randomised them in a 1:1 ratio to receive either iguratimod 25 mg twice daily or hydroxychloroquine 200 mg twice daily for 24 weeks. The primary endpoint was the Sjögren’s Syndrome Responder Index-30 response at week 24, with secondary outcomes including the Sjögren’s Tool for Assessing Response, the EULAR Sjögren’s Syndrome Disease Activity Index, the EULAR Sjögren’s Syndrome Patient Reported Index and changes in key serological biomarkers. A total of 66 patients completed the study, with 31 in the iguratimod group and 35 in the HCQ group.
While the primary endpoint showed a numerically higher response rate with iguratimod than with hydroxychloroquine (57.9% vs 40.0%), the difference did not reach statistical significance. However, iguratimod demonstrated clear superiority across several important secondary measures. Patients receiving IGU were significantly more likely to achieve a response on the Sjögren’s Tool for Assessing Response (39.5% vs 15.0%) and on the EULAR Sjögren’s Syndrome Disease Activity Index (21.1% vs 5.0%), indicating greater improvement in systemic disease activity. Iguratimod was also associated with a significantly greater reduction in serum IgG levels, supporting its impact on B-cell–driven immune dysregulation, a central feature of pSS pathophysiology.
These clinical findings are consistent with the known mechanisms of action of iguratimod. The drug selectively inhibits cyclooxygenase-2, leading to reduced prostaglandin synthesis and downstream anti-inflammatory effects. It also suppresses the production of multiple pro-inflammatory cytokines and reduces immunoglobulin production by B cells, thereby limiting immune-mediated tissue damage. Beyond its immunological actions, iguratimod promotes osteoblast differentiation and accelerates bone formation, which may be relevant for long-term musculoskeletal health in patients with chronic inflammatory disease.
In terms of safety, adverse events were reported more frequently in the iguratimod group than in the hydroxychloroquine group (60.6% vs 37.8%), but most events were mild in severity and treatment was generally well tolerated over the 24-week period. Taken together, the results suggest that iguratimod monotherapy can provide meaningful improvements in composite, systemic and serological outcomes in patients with active primary Sjögren’s syndrome. The data position iguratimod as a promising therapeutic option, particularly for patients with hypergammaglobulinaemia and features of B-cell hyperactivity, and highlight the need for larger, longer-term studies to confirm efficacy and clarify its role in routine clinical practice.
References
- Chen X, Zhang T, Meng L, Xu C, Jiang L, Wang G, Hou T, Wang H, Han Y, Guan Y, Wang Y, Xue J. Efficacy and safety of iguratimod in patients with primary Sjögren’s syndrome: a multicentre randomised controlled trial. RMD Open. 2025 Dec 21;11(4):e006180.
- Guo J, Chen Y, Wang S, Jiang T, Wang Y, Wu H, et al. Iguratimod alleviated Sjögren’s syndrome through regulating macrophage polarization. Rheumatology & Autoimmunity. 2025;5(4):309–20.