Complement inhibitors for age-related macular degeneration

Area of Science:

• Ophthalmology
• Immunology
• Genetics

Background:

• Age-related macular degeneration (AMD) is a leading cause of vision loss globally, with increasing incidence in aging populations.
• Overactivity of the complement system is implicated as a key driver in AMD development and progression.
• Novel therapeutics targeting complement pathways are emerging for AMD treatment.

Purpose of the Study:

• To assess the efficacy and safety of complement inhibitors for preventing or treating advanced AMD.
• To evaluate the impact of complement inhibition on visual acuity, lesion progression, and adverse events.

Main Methods:

• Systematic review and meta-analysis of randomized controlled trials (RCTs) involving complement inhibitors for advanced AMD.
• Searched multiple databases up to June 2022, including Cochrane Library, MEDLINE, and ClinicalTrials.gov.
• Included 10 RCTs with 4052 participants, evaluating intravitreal (IVT) and intravenous agents against sham or placebo.

Main Results:

• Intravitreal pegcetacoplan meaningfully reduced geographic atrophy (GA) lesion growth by 19.2% (monthly) and 14.8% (every-other-month) compared to sham.
• Intravitreal avacincaptad pegol showed probable reduction in GA lesion growth (25.6-30.5%), particularly in extrafoveal/juxtafoveal cases.
• No complement inhibitor demonstrated meaningful improvement in best-corrected visual acuity (BCVA); potential increased risk of macular neovascularization (MNV) and endophthalmitis observed.

Conclusions:

• Intravitreal pegcetacoplan and avacincaptad pegol show potential in slowing GA progression, but do not improve visual function in advanced AMD.
• Complement inhibition may be associated with emergent risks, including MNV and a small risk of endophthalmitis.
• Further research is needed to establish optimal dosing, long-term efficacy, safety, and cost-effectiveness of these therapies.