Combination of leflunomide and hydroxychloroquine reduces disease activity in Sjögren’s disease

At week 24, treatment with a combination of leflunomide and hydroxychloroquine resulted in a significant reduction in disease activity, as measured by the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), compared with placebo. The combination also led to significant improvements in several immunological markers.

To date, an unmet need for effective treatments for primary Sjögren’s disease remains [1]. Following positive results in a previous study (EudraCt2014-003140-12), the combination of leflunomide and hydroxychloroquine was tested in the phase 2b, placebo-controlled RepurpSS-II trial (EudraCt: 2020- 001933-11). This 24-week trial was followed by a subsequent single-arm crossover and a 24-week open-label extension.

Dr Wing-Yi Wong (University Medical Center Utrecht, the Netherlands) presented the results of the randomised phase involving 46 adult participants. The primary endpoint was the change in ESSDAI score at week 24.

Participants had a median age of 55 and were over 90% female. Baseline ESSDAI scores averaged 9.52 in the active arm versus 9.88 in the placebo arm. Median serum IgG levels were 12.7 g/L and 14.1 g/L, respectively.

“We found a statistically significant improvement in the ESSDAI score (P=0.001), with an effect size of -4.135 points in the treatment group,” Dr Wong reported. Significant benefits were also seen for serum IgG (P=0.016), rheumatoid factor (P=0.013), and C4 levels (P=0.031).

Exploratory endpoints, including the Composite of Relevant Endpoints for Sjögren's Syndrome (CRESS) and the Sjögren’s Tool for Assessing Response (STAR), also favoured the combination treatment (P=0.046 and P=0.007, respectively, in Pearson’s chi-square test).

“The total number and severity of adverse events (AEs) were comparable between the 2 groups,” Dr Wong stated regarding safety. However, 3 patients in the active group discontinued due to AEs versus none in the placebo group. The most frequent AEs were gastrointestinal discomfort, COVID-19, and the common cold.

“The RepurpSS-II study confirmed the safety and efficacy of 24 weeks of leflunomide and hydroxychloroquine therapy in patients with primary Sjögren’s disease with moderate-to- high disease activity,” Dr Wong concluded.

1. Wong WY, et al. RepurpSS-II: Validation of leflunomide-hydroxychloroquine combination therapy in patients with primary Sjögren’s Disease: A double-blinded, placebo-controlled, randomized LB0005, EULAR 2025, 11–14 June, Barcelona, Spain.

Copyright ©2025 Medicom Medical Publishers



Posted on 8 August 202525 August 2025