Evolution of outcome assessment in clinical trials of rheumatoid arthritis: A scoping review

To identify, map, and synthesize the outcomes reported in patients with rheumatoid arthritis and describe how these outcomes have changed over time throughout the 20th and 21st centuries.

A scoping review was conducted according to the Joanna Briggs Institute methodology and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Electronic searches were performed in PubMed/MEDLINE, Embase, PEDro, and Google Scholar from January 1989 to May 2026. Randomized clinical trials involving adults with rheumatoid arthritis were eligible. Five independent reviewers performed study selection and data extraction. Reported outcomes were classified into conceptual domains and analyzed chronologically to identify temporal trends in outcome assessment.

The search identified 5209 records, of which 611 randomized clinical trials met the eligibility criteria. Disease activity outcomes remained the most consistently reported across all decades, evolving from individual clinical measures toward standardized composite indices, including ACR response criteria, DAS, DAS28, SDAI, and CDAI. Outcome assessment progressively expanded to incorporate structural damage, patient-reported outcomes, physical function, health-related quality of life, imaging, laboratory biomarkers, safety, and health-economic measures. Recent trials increasingly emphasized remission, treat-to-target strategies, advanced imaging techniques, validated patient-reported outcome measures, and biomarker-based assessments, reflecting a more comprehensive and patient-centered approach to rheumatoid arthritis management.

Outcome assessment in rheumatoid arthritis clinical trials has evolved substantially over the past four decades, transitioning from symptom-focused evaluation to multidimensional assessment encompassing clinical, structural, functional, biological, and patient-centered domains. This review synthesizes evidence from 611 randomized clinical trials and provides a comprehensive mapping of the historical evolution of outcome measurement, offering a valuable reference for future clinical research and the development of standardized core outcome sets.