Eye inflammation linked to geographic atrophy drug remains a mystery

There is still no explanation for rare cases of uveitis (a collection of inflammatory conditions that affect the internal tissues of the eye) and retinal vascular occlusion (blockage of retinal blood vessels) with pegcetacoplan (Syfovre), a newly approved treatment for geographic atrophy (GA). The incidents came to light when the American Society of Retina Specialists (ASRS) distributed a memo to its members in July, alerting them to the above adverse events. The mystery remained unsolved as 2023 came to a close. 

The ASRS Research and Safety in Therapeutics (ReST) Committee received an initial incident report July 3. By the end of July at the ASRS annual meeting the number of reported incidents had risen to 21. But the reason for the inflammation remains elusive, according to ReST chairperson Andre Witkin, MD, of Tufts University and the New England Eye Center in Boston. “I don’t think I or anyone else knows the reason these rare events have been happening,” Witkin told MedPage Today. “We have talked about some possible theories, but no one knows.”   Next month, the Journal of VitreoRetinal Diseases will publish a detailed report on the cases of inflammation, co-authored by members of the ReST committee. The article will include the current number of incident reports, details about the cases, and hypotheses about the potential causes. Possible explanations include patient-specific characteristics that make them more susceptible to one or more components of the drugs, as well as infection associated with complement inhibition. Both pegcetacoplan and avacincaptad pegol (Izervay), the newest approved drug for GA, inhibit the complement system, a group of proteins that normally work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. Until recently, all of the reported incidents involved pegcetacoplan, but avacincaptad pegol has been involved in at least one case, said Witkin. That case involved a patient who received pegcetacoplan in one eye and avacincaptad pegol in the other.

Ophthalmologists’ reaction to the as-yet unexplained intraocular inflammation continues to evolve. “I think there are varying opinions about how people feel about these drugs,” said Witkin. “They fill a previously unfilled niche for a disease that doesn’t have any other treatment, so I think there’s certainly some role for them. It remains to be seen how they are ultimately going to fit into our practices.” 

Edited by D. Wilcox BSN RN, and M. Kaplan, PhD. 

Source: Charles Bankhead, MedPage Today, December 27, 2023; see source article