Researchers at UMC Utrecht have identified the first effective conventional treatment for systemic Sjögren's disease—a pair of existing arthritis medications that have quietly been sitting in pharmacy shelves for decades. In a randomized, placebo-controlled trial called RepurpSS-II, patients taking leflunomide and hydroxychloroquine experienced a clinically meaningful reduction in disease activity over 24 weeks, offering hope to the roughly 0.5% of the global population affected by this chronic autoimmune condition.
Sjögren's disease strikes primarily women and damages the body's moisture-producing glands, leaving patients with severe dryness in the eyes and mouth—symptoms typically managed only with artificial tears and saliva substitutes. But the disease often advances beyond these local symptoms. Some patients develop systemic complications involving the skin, lungs, and kidneys, while living with a heightened risk of non-Hodgkin lymphoma. Until now, doctors had no way to suppress this broader disease activity, making the Utrecht findings genuinely transformative.
The trial enrolled 46 patients across 12 Dutch clinical centers, dividing them randomly into two groups. Those receiving the two-drug combination showed disease activity scores that dropped by an average of 4.135 points more than the placebo group after 24 weeks of daily oral treatment—a difference that crossed the threshold of clinical significance (p=0.0012). What makes these results particularly compelling is that the study was conducted without any background immunosuppressive therapy. This methodological choice allowed researchers to isolate and measure the true effect of leflunomide and hydroxychloroquine, avoiding the murkiness that clouds trials where patients receive multiple overlapping treatments.
Joel van Roon, the immunologist and principal investigator at UMC Utrecht's Center for Translational Immunology, described the breakthrough in careful but hopeful terms: "RepurpSS-II represents the first successful conventional DMARD therapy in Sjögren's syndrome in a randomized, placebo-controlled setting without background immunosuppressive medication." The two drugs, both established disease-modifying anti-rheumatic drugs (DMARDs), have been safely used in arthritis patients for years. This prior safety track record and their affordability make them especially promising for widespread adoption.
Researchers also evaluated the combination using newer assessment tools specifically designed for Sjögren's syndrome research—the STAR and CRESS scores—which capture both objective dryness measurements and patient-reported outcomes alongside disease activity. On these measures, too, more patients on active treatment responded positively. The drug combination was generally well tolerated, with gastrointestinal complaints being the most common side effect in both treatment and placebo groups. One serious adverse event, a heart attack in the treatment arm, occurred during the trial but was deemed unrelated to the study medication following cardiac analysis.
Secondary endpoints such as dryness, fatigue, and pain did not show clear improvement, suggesting that while the drugs successfully suppress systemic disease activity, they may not address every symptom patients experience. Still, suppressing systemic disease activity itself—something doctors could not do before—represents a watershed moment. The RepurpSS-II findings not only offer an immediately applicable treatment option that could reach patients within months but also provide a foundation for future research into the biological mechanisms driving Sjögren's disease. For patients who have endured years without effective systemic therapies, this represents the kind of practical, evidence-based hope that Meridia's readers deserve to hear about.