Early intensification versus step-up biologic strategies in systemic juvenile idiopathic arthritis: a Bayesian network meta-analysis of remission and safety outcomes.

OBJECTIVE: To compare the relative effects of different treatment strategies for Systemic Juvenile Idiopathic Arthritis (sJIA) on clinical inactivity (CID)/remission and safety using a Bayesian network meta-analysis and to rank the treatment options. METHODS: PubMed, Embase, Web of Science, the Cochrane Library, and Scopus were systematically searched from inception to October 2025 according to PRISMA 2020 and PRISMA-NMA specifications. Randomized controlled trials (RCTs), prospective cohorts, and retrospective/registry studies were included. The primary outcome was the CID/remission rate, and the secondary outcome was the incidence of adverse events (AEs) (normalized per patient-year). Random-effects and Bayesian hierarchical network models were used. Risk of bias was assessed using ROB-2 and NOS, and the certainty of evidence was assessed using GRADE. RESULTS: A total of 2,408 records were retrieved. After deduplication, 1,088 records were screened for titles/abstracts, and 200 were reviewed in full text. Fifteen studies (total sample size 1,548) were ultimately included. A pooled analysis showed that approximately two-thirds of patients achieved CID/remission during follow-up (random-effects model). Stratification suggested that an early IL-1/IL-6 strategy had a more favorable response rate. A network meta-ranking analysis (SUCRA) showed that early IL-1/IL-6 blockade ranked first, followed by anakinra and canakinumab; tocilizumab was in the middle; and conventional care and mixed biologic strategies ranked last. The overall AE rate was low and consistent across studies; IL-1/IL-6 targeted drugs had a favorable safety profile. Multiple sensitivity analyses and cumulative evidence analysis supported the robustness of the conclusions. CONCLUSION: In sJIA, immediate intensive IL-1/IL-6 therapy at diagnosis is more effective than a step-up approach in achieving and maintaining CID/remission, while also having an acceptable safety profile, supporting the initial "target-to-treat (T2T)" strategy. Future prospective studies and biomarker-stratified validation of each strategy are needed.