Specific genetic factors may lead to negative response to AREDS formulation

FLORENCE, Italy — High-dose zinc, as in the AREDS and AREDS2 formulations, may be harmful in patients with high complement factor H and low age-related maculopathy susceptibility 2 risk alleles, according to one speaker.

“There is considerable evidence that response to AREDS supplements is influenced by genetic risk,” Carl C. Awh, MD, said at the FLOREtina meeting.

Carl C. Awh

In a first outcome analysis of 989 AREDS patients using combined complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genetic risk, Awh and co-authors demonstrated that patients with low CFH and high ARMS2 risk had very good results as opposed to patients with high CFH and low ARMS2.

“In this group, patients treated with AREDS formulation had 40% progression to advanced AMD at 7 years compared to 17% in the placebo group. We believe these outcomes are primarily related to the high dose of zinc component of the AREDS formulation,” Awh said.

Following the “vigorous response” of the AREDS study group, disproving these finding in report 38, Awh and co-authors presented a peer-reviewed alternative analysis of AREDS 38 data, based on the genotype groups of the previous publication.

“We found again that patients with low CFH and high ARMS2 had an odds ratio of AMD progression of 0.45, suggesting tremendous benefit from supplementation, while those with high CFH and low ARMS2 had an odds ratio of 2.14, suggesting harm,” Awh said.

“These are not small numbers. Almost 20% of the 1,237 patients included in report 38 were in this group,” he said.

There is evidence to warrant further investigation, including a prospective clinical trial, he said. In the meantime, he suggested withholding high-dose zinc in these high-risk patients. – by Michela Cimberle

Disclosure: Awh reports he is a consultant to Alcon, ArcticDx, Bausch + Lomb, ForSight, Genentech, GlaxoSmithKline, Janssen, Katalyst, Regeneron, Synergetics, Tyrogenex and Volk.