A systematic review of clinical trial designs and outcome measures in Sjögren's disease randomized trials.

Objective: To systematically review all existing SjD-related instruments reported in clinical trials for Sjögren's disease (SjD).

Methods: We systematically searched Medline (Pubmed) and EMBASE between 2002 and March 2023 to identify all randomized controlled trials (RCTs) using both a manual approach and artificial intelligence software (BIBOT). We extracted all the instruments used as primary or secondary outcomes, and assessed if the study achieved or not to improve the outcome. We also classified the instruments according to the recently preliminary defined outcome domains.

Results: Among 5,420 references, 60 RCTs were including, focusing either on overall disease manifestations (53%) or on a single organ/symptom (eg. dry eyes (17%), xerostomia (15%), fatigue (12%), or pulmonary function (3%). Primary outcomes included measures of oral or ocular dryness, patient-reported outcomes (PRO), systemic activity, and other outcomes (7%). Common instruments used were ESSDAI, ESSPRI, Schirmer's test unstimulated salivary flow, and IgG levels. ESSDAI was a primary outcome in 11 studies, with 45% of studies reaching significance, while none of the 16 studies with ESSDAI as a secondary outcome reached significance. PROs were the primary outcome in 34 studies. Glandular function measurements varied, with unstimulated salivary flow as the most common measured outcome. Life impact was assessed more frequently as a secondary outcome. Only two studies focused on biological activity.

Conclusions: Our review highlighted the heterogeneity of SjD, in the designs and outcomes. The use of PROs and composite outcomes has increased in recent years, highlighting a shift from objective dryness measures to more holistic patient-centered outcomes.