Background With the exponential growth of systematic reviews and meta-analyses on RA pharmacotherapy, a comprehensive and up-to-date assessment of methodological quality is urgently needed to gauge the credibility of this evidence base. Objective This protocol describes a meta-epidemiological study that will systematically appraise the methodological quality of published systematic reviews and meta-analyses of RA pharmacotherapy (csDMARDs, bDMARDs, and tsDMARDs) using the AMSTAR 2 instrument and explore study-level factors associated with methodological quality. Methods We will systematically search PubMed, Embase, the Cochrane Library and three Chinese databases-China National Knowledge Infrastructure (CNKI), Wanfang Data and China Science and Technology Journal Database-from inception to June 1, 2026. Two independent reviewers will screen studies, extract data and assess methodological quality using the AMSTAR 2 instrument; an overall rating (high, moderate, low, critically low) will be derived for each review. Binary logistic regression comparing “Adequate” (High/Moderate) versus “Inadequate” (Low/Critically Low) reviews will be used for the primary analysis, with ordinal logistic regression fitted as a pre-specified exploratory analysis; pre-specified sensitivity and robustness analyses (including penalized and Bayesian estimation for sparse categories) will test the stability of findings. Results The results will provide a descriptive overview of the methodological quality landscape, highlighting common strengths and critical weaknesses across published RA meta-analyses. The regression analysis will quantify the relationship between specific study characteristics and methodological quality. Conclusion This study will provide a comprehensive, cross-drug-class AMSTAR 2-based methodological assessment of the RA pharmacotherapy evidence-synthesis field, complementing prior appraisals limited to specific complementary or single-agent interventions. The findings will offer clinicians and guideline developers a graded framework for judging evidence credibility and will provide empirical, actionable guidance for researchers to enhance the design, conduct, and reporting of future systematic reviews in RA.
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Yang et al. (2026) studied this question.
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