#4-72E. Rethinking Sjögren’s: The Power of Combination Therapy (Lancet Rheumatol, 2026)

Are we finally close to a widely accessible systemic treatment for Sjögren’s disease? Despite severe glandular and systemic manifestations, patients with Sjögren's disease have long lacked established systemic therapies. This phase 2b, double-blind, randomized controlled trial evaluated the efficacy and safety of repurposing leflunomide and hydroxychloroquine as a combination therapy for patients with active systemic Sjögren’s disease. The most crucial clinical finding is that this combination significantly reduced systemic disease activity, lowering ESSDAI scores by 4.135 points compared to placebo at 24 weeks, notably without the confounding effect of background immunomodulatory therapies. When critically appraising this study, physicians should note that the trial enrolled a small sample of 46 patients—falling short of its predefined target—and restricted inclusion to those with an ESSDAI of 5 or greater, meaning the results may not generalize to patients with low systemic activity but high subjective symptom burden. Nevertheless, this study provides highly relevant clinical insights, as it demonstrates an effective, affordable, and readily available oral treatment strategy that could immediately reshape daily practice for managing moderate-to-severe Sjögren’s disease.

Citation: Wing-Yi Wong, Joël A G van Roon, et al. Repurposing leflunomide and hydroxychloroquine to treat Sjögren’s disease (RepurpSS-II): a randomised, double-blind, placebo-controlled, phase 2b trial. The Lancet Rheumatology. 2026. DOI: 10.1016/S2665-9913(26)00075-5

Disclaimer: This audio summary is based on personal interpretation and does not guarantee the exact content of the original paper. Please refer to the original article for details.