gms | German Medical Science

Background: Earlier this year, the FDA has approved pegcetacoplan injections for the treatment of geographic atrophy (GA) secondary to AMD. Phase-III trials have shown a reduction in GA lesion growth in treated subjects. However, given the relatively high prevalence of the disease and risks associated with frequent injections, it would be extremely valuable to know which subgroups of patients would benefit most from this treatment. With this study, we hope to gain more insight in the levels of complement components and activation products in AMD patients.

Methods: Complement components and activation products (CFI, CFH, C2, C5, CFB, CFD, Bb, C3a, C3bc, C3bBbP, C4D, C5a, TCC, and properdine) were measured in plasma samples of 43 patients with AMD (18 late AMD and 25 early/intermediate AMD) in a diagnostic setting. We used descriptive analyses to look for patterns and combinations of elevated measurements.

Results: In 40 patients (93%), at least 1 factor was elevated. The most frequently elevated factor was C3bBbP (79%), followed by CFH (45%) and TCC (40%). For C2, C3bc, C4D, and Properdine, elevated levels were only found in 5% or less. We further noticed that the combination of elevated CFH, C5, CFB and C3bBP levels occurred relatively frequently with 14 patients (33%) having elevated levels of at least 3 of these factors.

Conclusion: We observed specific patterns of elevated levels of complement activation products and components. We are planning future studies, including prospective evaluations of these factors over time with the aim to identify a set of complement components and activation markers that can serve as biomarkers for progression. These would ultimately be ideal candidates for therapy development. In addition, insight in how these levels change during the course of the disease could have implications for patient selection and the window of opportunity for treatment with complement inhibitors.