leflunomide + hydroxychloroquine

Leflunomide + hydroxychloroquine is a combination of two conventional disease-modifying antirheumatic drugs (DMARDs) being repurposed for the treatment of primary Sjögren's syndrome (pSD). Leflunomide is a pyrimidine synthesis inhibitor that targets the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), thereby inhibiting the proliferation of activated lymphocytes. Hydroxychloroquine is an immunomodulator that interferes with lysosomal activity and inhibits Toll-like receptor (TLR) signaling, specifically TLR7 and TLR9. The combination is hypothesized to exert additive immune-inhibitory effects, specifically targeting type I interferon-associated proteins and reducing B cell hyperactivity, which are key drivers of Sjögren's pathology. Clinical efficacy has been demonstrated in the RepurpSS-I and RepurpSS-II trials, showing significant reductions in systemic disease activity as measured by the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).

Other names

leflunomide-hydroxychloroquine combination therapy