Primary Sjögren’s syndrome is an autoimmune disease affecting exocrine glands resulting in dryness of the eyes and the mouth with multiple systemic complications in different organs. In 30% to 50% of the patients, systemic and extra-glandular manifestations may develop and include fatigue, vasculitis, peripheral neuropathy, affected joint, kidney malfunction and interstitial lung disease. Moreover, primary Sjögren’s syndrome patients have a 10 to 20-fold higher risk of developing B cell lymphomas, conferring shorter life expectancy.
The negative impact on quality of life is prominent and primary Sjögren’s syndrome represents a significant health and economic burden. To date, there is no treatment with demonstrated efficacy for the systemic manifestations of primary Sjögren’s syndrome and only symptomatic treatments are commercially available. Classical immunosuppressive drugs are used in patients with severe organ involvement but with variable results.
There are several factors that may hamper the development of successful drugs for primary Sjögren’s syndrome. As a multiorgan disease, clinical manifestations and biological disturbances are considerably heterogeneous among individuals. Such heterogeneity provides a major challenge to designing clinical trials measuring the success of an intervention using a “one size fit all” outcome measure. Thus, it is of paramount importance to identify new sensitive clinical endpoints, define endotype-specific biomarkers and develop an original design for an innovative multi-arm clinical trial.