Quality of Systematic Reviews with Network Meta-Analyses on JAK Inhibitors in the Treatment of Rheumatoid Arthritis: Application of the AMSTAR 2 Scale.

Abstract

<b>Background/Objective:</b> Systematic reviews (SRs) with network meta-analysis (NMA) support evidence-based decision-making by enabling both direct and indirect comparisons across multiple interventions. Given the expanding use of Janus kinase (JAK) inhibitors in rheumatoid arthritis (RA), the methodological rigor of SRs with NMA is essential for trustworthy conclusions. This study is aimed at evaluating the methodological quality of SRs with NMA assessing the efficacy and/or safety of JAK inhibitors in RA. <b>Methods:</b> PubMed and Embase were searched for full-text SRs with NMAs evaluating JAK inhibitors as a therapeutic class in RA. Eligible publications were English-language articles reporting efficacy and/or safety outcomes. Narrative reviews, letters, duplicates, reviews focused on a single JAK inhibitor, and reviews without quantitative synthesis were excluded. Three independent reviewers assessed methodological quality using AMSTAR 2. Descriptive statistics were used to summarize findings. <b>Results:</b> Of the 222 records identified, 18 SRs with NMA met the inclusion criteria: 5 focused on efficacy, 5 on safety, and 8 assessed both. The most consistently fulfilled AMSTAR 2 items were a clearly defined PICO question (100%), duplicate study selection (100%), and reporting of conflicts of interest (100%). Common shortcomings included lack of protocol registration (44%), incomplete reporting of the search strategy (39%), and absence of publication bias assessment (50%). Risk-of-bias assessment varied by review focus: all safety reviews complied (100%), compared with 20% of efficacy reviews and 37% of mixed reviews. <b>Conclusions:</b> Most SRs with NMA of JAK inhibitors in RA present relevant methodological limitations, particularly in protocol registration, search reporting, and risk-of-bias assessment. Methodological standards were generally higher in safety-focused reviews, underscoring the need for more consistent and rigorous conduct and reporting, especially in efficacy and mixed reviews, to strengthen confidence in NMA-derived conclusions.