Biologic Switching Strategies for Anti-Tumor Necrosis Factor Alpha Refractory Noninfectious Uveitis:: Systematic Review and Meta-Analysis of Clinical Approach.

TOPIC: This study aimed to investigate switching strategies of biologics in noninfectious uveitis (NIU) refractory to anti-tumor necrosis factor alpha (TNFα) agents. CLINICAL RELEVANCE: Noninfectious uveitis often requires biologic therapy when conventional immunosuppression fails. Tumor necrosis factor alpha inhibitors, such as adalimumab and infliximab, are commonly used as first-line biologics, but up to one-third of patients experience inadequate responses. METHODS: We conducted a systematic review and meta-analysis to evaluate clinical outcomes following biologic switching in patients with NIU refractory to anti-TNFα therapy. This review was registered at PROSPERO (CRD420251071702). PubMed, EMBASE, and Cochrane Library were searched through January 5, 2025. Switching strategies were categorized as either intraclass (switching between anti-TNFα agents) or interclass (switching from an anti-TNFα agent to a different class biologic). Pooled response rates were compared between the two approaches. Risk of bias was assessed using the Joanna Briggs Institute (JBI) checklists for case reports/series and the Newcastle-Ottawa Scale for comparative studies. Certainty of evidence for primary outcome was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: A total of 136 studies (129 case reports/series and 7 comparative studies) were included for systematic review, with 89 studies contributing to the meta-analysis. Using the JBI tool, 11 of 77 studies had high risk of bias, while the remainder were of at least fair quality. Among comparative studies, one-third had moderate risk of bias, while the rest were rated as low risk. The overall pooled response rate after switching was 83% (95% confidence interval [CI]: 76%-90%; I2 = 30.2%; 466 patients). Intraclass switching showed a pooled response rate of 77% (95% CI: 65%-87%; I2 = 36%), which was lower than that of interclass switching showing 89% (95% CI: 80%-96%; I2 = 18%, P = 0.0995). Sensitivity analyses showed a 71% (95% CI: 59%-82%, I2 = 54.5%) pooled response rate for intraclass switch and 85% (95% CI: 77%-93%, I2 = 32.8%) for interclass switch, revealing statistically significant difference (P = 0.044). The certainty of evidence was graded as low for the overall pooled response rate after switching. CONCLUSIONS: Both intraclass and interclass switching strategies appear effective, with interclass switching showing higher response rates; however, these findings warrant cautious interpretation given the limited certainty of evidence. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.