Biologic Switching Strategies for Anti-Tumor Necrosis Factor Alpha Refractory Noninfectious Uveitis:: Systematic...

This study aimed to investigate switching strategies of biologics in noninfectious uveitis (NIU) refractory to anti-tumor necrosis factor alpha (TNFα) agents.

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.

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.

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.

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.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.