The effect of complement C3 or C5 inhibition on geographic atrophy secondary to age-related macular degeneration: A living systematic review and meta-analysis

Anubhav Garg; Keean Nanji; Felicia Tai; Mark Phillips; Dena Zeraatkar; Sunir J Garg; SriniVas R Sadda; Peter K Kaiser; Robyn H Guymer; Sobha Sivaprasad; Charles C Wykoff; Varun Chaudhary

doi:10.1016/j.survophthal.2023.11.008

The effect of complement C3 or C5 inhibition on geographic atrophy secondary to age-related macular degeneration: A living systematic review and meta-analysis

Surv Ophthalmol. 2024 May-Jun;69(3):349-361. doi: 10.1016/j.survophthal.2023.11.008. Epub 2023 Nov 24.

Authors

Affiliations

¹ Division of Ophthalmology, Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
² Division of Ophthalmology, Department of Surgery, McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
³ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
⁴ Mid Atlantic Retina, The Retina Service of Wills Eye Hospital, Philadelphia, PA, USA.
⁵ Department of Ophthalmology, David Geffen School of Medicine at University of California, Los Angeles, CA, USA; Doheny Eye Institute, Los Angeles, CA, USA.
⁶ Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.
⁷ Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia; Department of Surgery (Ophthalmology), University of Melbourne, Melbourne, Australia.
⁸ Institute of Ophthalmology, University College London, UK; NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK.
⁹ Retina Consultants of Texas, Houston, TX, USA; Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA.
¹⁰ Division of Ophthalmology, Department of Surgery, McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada. Electronic address: vchaudh@mcmaster.ca.

PMID: 38008405
DOI: 10.1016/j.survophthal.2023.11.008

Abstract

With the introduction of therapies to treat geographic atrophy (GA), GA management in clinical practice is now possible. A living systematic review can provide access to timely and robust evidence synthesis. This review found that complement factor 3 and 5 (C3 and C5) inhibition compared to sham likely reduces change in square root GA area at 12 months and untransformed GA area at 24 months. There is likely little to no difference in the rate of systemic treatment-emergent adverse events compared to sham. C3 and C5 inhibition, however, likely does not improve best-corrected visual acuity (BCVA) at 12 months, and the evidence is uncertain regarding change in BCVA at 24 months. Higher rates of ocular treatment emergent adverse effects with complement inhibition occur at 12 months and likely at 24 months. Complement inhibition likely results in new onset neovascular age-related macular degeneration at 12 months. This living meta-analysis will continuously incorporate new evidence.

Keywords: Age-related macular degeneration; Avacincaptad pegol; C3; C5; Complement; Eculizumab; Geographic atrophy; Living systematic review; Meta-analysis; Pegcetacoplan.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Complement C3* / antagonists & inhibitors
Complement C3* / metabolism
Complement C5* / antagonists & inhibitors
Complement Inactivating Agents* / therapeutic use
Geographic Atrophy* / diagnosis
Geographic Atrophy* / drug therapy
Geographic Atrophy* / etiology
Geographic Atrophy* / physiopathology
Humans
Macular Degeneration / drug therapy
Visual Acuity

Substances

Complement C3
Complement C5
Complement Inactivating Agents