Clinical Report: Factors Influencing Discontinuation of GA Complement Inhibitor Therapy

Overview

A large retrospective analysis of over 20,000 eyes treated for geographic atrophy (GA) reveals that baseline coexisting neovascular AMD and poor initial visual acuity are significantly associated with early discontinuation of intravitreal complement inhibitor therapy. Discontinuation rates increase over time regardless of the specific agent used.

Background

Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a progressive condition treated with intravitreal complement inhibitors such as pegcetacoplan and avacincaptad pegol. Maintaining long-term adherence to these therapies is challenging, with attrition increasing over time. Understanding baseline factors that predict treatment discontinuation can help optimize patient management and outcomes.

Data Highlights

Key Findings

• Treatment discontinuation, defined as a gap exceeding 120 days, increased progressively over 18 months regardless of the complement inhibitor used.
• Baseline coexisting neovascular AMD was significantly associated with higher rates of treatment discontinuation.
• Poor baseline visual acuity correlated strongly with early therapy cessation.
• More than half of patients had foveal involvement at baseline, which may impact treatment persistence.
• Differences in FDA approval dates and follow-up duration limit direct long-term comparisons between pegcetacoplan and avacincaptad pegol.
• Further longitudinal studies are needed to clarify reasons for discontinuation, including disease progression, adverse events, treatment fatigue, or decision-making factors.

Clinical Implications

Clinicians should be aware that patients with baseline neovascular AMD and poor visual acuity are at increased risk of discontinuing GA complement inhibitor therapy. Monitoring and supportive strategies may be necessary to improve long-term adherence. Understanding individual patient factors can guide personalized treatment plans and follow-up schedules.

Conclusion

This large real-world analysis highlights significant attrition in GA complement inhibitor therapy over time, with baseline clinical characteristics influencing discontinuation. Further research is essential to elucidate underlying causes and improve patient retention.

References

1. Sambhara D et al. 2025 Retina World Congress -- Who Stops GA Therapy—and Why