Evolution and prospects for the definition of clinically useful endpoints in Sjögren disease

Outcomes in Sjögren disease (SjD) have ranged from diverse symptom scales to the validated EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), which now provide a common framework for evaluating symptoms and systemic activity. In this review, we trace the evolution of trial endpoints and highlight that the first positive trials used the ESSDAI as the primary endpoint. We examine how systemic activity does not necessarily correlate with patient-reported outcomes (PROs), and stress that both dimensions must be evaluated to capture the full spectrum of SjD. New tools are emerging, such as the Sjögren's Tool for Assessing Response (STAR), a composite endpoint requiring improvement in both systemic activity and either PROs or objective sicca measures. Although still recent, STAR could be refined, as current thresholds for ESSDAI and ESSPRI, which were validated as clinically meaningful, could contribute to a substantial placebo effect. Moreover, we argue that future developments should also address organ damage, flares, histological response, and the link between outcome measures and major events such as lymphoma or mortality.