Aflibercept, brolucizumab, ranibizumab ’ideal’ anti-VEGF options for neovascular AMD
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Anti-VEGF regimens that include aflibercept, brolucizumab and ranibizumab were ideal in both safety and efficacy in patients with neovascular age-related macular degeneration, according to a study.
“There are currently large numbers of therapeutic regimens of anti-VEGF therapy with different drugs, dosages and therapeutic strategies, while controversies remain regarding the ideal drug and optimum therapeutic strategy,” Yun Zhang, MD, of the department of ophthalmology at West China Hospital in China, and colleagues wrote in Frontiers in Pharmacology. “However, it is difficult to acquire comparative efficacy and safety profiles from current trials due to the lack of head-to-head trials. Meanwhile, several problems in published meta-analyses, such as indiscriminate merger, inaccurate dosage distinction and redundancy inclusion, remain to be resolved with more precise analysis.”
Zhang and colleagues conducted a network meta-analysis of 27 randomized controlled trials, which included 10,484 participants and 18 treatments, to determine the comparative efficacy and safety of anti-VEGF monotherapy and identify its utilization and prioritization in patients with nAMD. Investigators sourced the trials from electronic PubMed, Embase and Cochrane Library databases and compared the recommended anti-VEGF agents, including aflibercept, bevacizumab, brolucizumab and ranibizumab in various therapeutic regimens.
The primary outcomes included the mean change in best-corrected visual acuity and the number of serious adverse events. Key secondary outcomes included the proportion of patients who gained greater than or equal to 15 letters or lost less than 15 letters in BCVA, the mean change in central retinal thickness and the mean number of injections. All outcomes were measured at 12 months.
Researchers found that intravitreal administration of aflibercept (2 mg bimonthly or treat and extend), ranibizumab (0.5 mg treat and extend) and brolucizumab (6 mg every 12 weeks or every 8 weeks) were associated with better visual efficacy.
Although “brolucizumab had absolute superiority in anatomical recovery of the retina and a relative advantage of safety, as well as good performance of aflibercept treat and extend,” according to study results, bevacizumab had a lower degree of efficacy and safety, which was determined to be statistically nonsignificant. The study also revealed that proactive regimens had better efficacy but slightly increased number of injections compared with reactive regimens.
“In the current landscape, based on the premise of equivalent efficacy and safety, the optimal choice of anti-VEGF monotherapies seems mandatory to obtain maximal benefit,” Zhang and colleagues concluded.
Perspective
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Irreversible vision loss from nAMD can cause patients to lose independence in their daily life and negatively impact mental health. This study reinforces what we’ve known about anti-VEGF injections but also sparks an important discussion about hurdles in patient compliance.
Not surprisingly, treatment with injections resulted in better visual acuity and anatomical results compared to photodynamic therapy. Similarly, proactive regimens such as treat and extend and monthly/bimonthly regimens were superior to as needed treatment. Although we should continue to emphasize the importance of follow-ups with retina specialists to preserve remaining vision, patient compliance plays a key role in visual outcomes.
Real-life circumstances make it difficult to apply the optimal injection frequency from this analysis of randomized clinical trials. It’s tough for patients with limited mobility or those with poor access to care to make frequent trips to a clinic. Even previously compliant patients may be hesitant to return every month for injections during a pandemic.
Ultimately, it is important to consider a patient’s relative risks and burdens to achieve maximum benefit from anti-VEGF injections. In the future it will be interesting to see if recently approved steady release port delivery systems can significantly improve patient compliance by reducing the frequency of clinic visits.
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