The pipeline of targeted therapies under clinical development for primary Sjogren's syndrome: A systematic review of trials

To date, no immunomodulatory drug has proved efficacious in primary Sjogren's syndrome (pSS). In pSS, difficulties in drug efficacy assessment is related to the large spectrum of clinical involvements (glandular/extraglandular involvement), to the lack of correlation between symptoms of dryness and glandular function assessed by objective measurements, as well as between symptoms and systemic complications of the disease. Severe organ manifestations are generally treated by off-label therapies in accordance with current practice and guidelines for Systemic Lupus Erythematosus or other connective-tissue diseases. Despite a much greater understanding of the pathogenesis of pSS, modern drug development has resulted in no approval of therapy so far. In this study, we performed a systematic review of all targeted therapies under clinical development in pSS, in 17 main online registries of clinical trials. Our search identified 264 trials, from which 25 targeted therapies for pSS were included. The molecules under current clinical development for pSS target B cells (n = 4), T cells or T/B cells costimulation (n = 5), inflammatory cytokines or chemokines and their receptors (n = 5), intracellular signalling pathways (n = 7) and various other targets identified in pSS (n = 4). The current drug development pipeline in pSS may lead to valuable strategies for the treatment of this currently difficult-to-treat disease.