Clinical trials in recent years have shown significant effectiveness of complement inhibitors for geographic atrophy (GA) treatment. Two complement inhibitor drugs have been approved by the Food and Drug Administration (FDA).
to compare and rank the different complement inhibitors in the treatment of GA secondary to age-related macular degeneration (AMD).
A systematic literature search was conducted in the Cochrane Central, Web of Science Core Collection, PubMed, LWW Medical Journals,
All randomized clinical trials evaluating the effectiveness of complement inhibitors in patients diagnosed with secondary GA in AMD were identified.
This study followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) network meta-analysis Checklist of Items and the Cochrane Risk of Bias Assessment Tool for assessing the study quality. Multiple authors independently coded all titles and abstracts, reviewed full-text articles against the inclusion and exclusion criteria, and resolved all discrepancies by consensus. Random-effects network meta-analyses were applied. Bayesian network meta-analysis was performed using the BUGSnet package in R (4.2.0).
The primary efficacy outcome was the change in GA lesion size (mm2) from baseline to month 12. The secondary efficacy outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to month 12. Safety outcome measures included the number of subjects with serious adverse events (SAEs) and macular neovascularization (MNV).
Ten randomized controlled trials including 4,405 participants and five complement inhibitors were identified. Comparison with sham and SUCRA analysis showed that avacincaptad pegol 2 mg (MD: −0.58, 95% CrI: −0.97 to −0.18, SUCRA: 93.55), pegcetacoplan monthly (MD: −0.38, 95% CrI: −0.57 to −0.20, SUCRA: 81.37), and pegcetacoplan every other month (MD: −0.30, 95% CrI: −0.49 to −0.11, SUCRA: 70.16) have significant changes in GA lesion reduction. No treatments showed significant changes in BCVA and SAE compared with sham. Pegcetacoplan monthly (OR: 4.30, 95% CrI: 1.48–16.72) increased the risk of MNV. Avacincaptad pegol 2 mg demonstrated favorable outcomes in terms of SAE and MNV.
Avacincaptad pegol 2 mg is the most effective complement inhibitor with better safety for the treatment of GA secondary to AMD.