Wet AMD Treatment Outcomes Look Misleadingly Better in Clinical Trials

In an ideal world, every patient would adhere to their medication dosage and frequency to a T — needless to say, that isn’t the case. An analysis presented at the 34^th Annual Scientific Meeting of the American Society of Retina Specialists (ASRS 2016) in San Francisco, California looked at “real world” outcomes with anti-vascular endothelial growth factor (VEGF) drugs to treat wet age-related macular degeneration (AMD).

Vision loss is a very real, potential outcome of AMD. Anti-VEGF drugs have shown to successful prevent retinal damage and central vision loss; however, adherence to treatment remains an issue. Outcomes vary when it comes to real-world versus randomized controlled trials. Real-world incidences have poor visual outcomes as well as a 20% to 30% dropout rate within the first year. In a presentation at ASRS 2016, Thomas Ciulla, MD, MBA, an ophthalmologist from Indiana, started off with the three questions the analysis aimed to answer:

1. What are the outcomes?

2. Who is at most risk for vision loss?

3. What is happening with patients lost to follow-up?

To evaluate the risk of vision loss as associated with baseline visual acuity (VA), Ciulla and colleagues reviewed 2,213 patients who were diagnosed with wet AMD at some point from January 2011 to July 2013. All of these patients — 63% female and an average age of 82 – had follow-up data available to July 2015. They had received at least three monthly injections during the first four months.

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Out of the patients, 70% received bevacizumab, 17% received ranibizumab, and 13% received aflibercept. The participants were categorized into cohorts by how long they remained available during follow-up: six months (97 patients), 12 months (195 patients), or 24 months (1,921 patients).

There were no meaningful differences in number of injections among the three cohorts. Those in the six-month group had an average of five injections, in the 12-month group it was seven injections, and in the 24-month group it was 12 injections.

In clinical trials, patients typical gain eight letters. However, the patients in the six-month group lost less than one letter. Patients who dropped out at six months did worse than those who dropped out at 12 months. This trend continued as those who dropped out at 12 months did worse than those who dropped out at 24 months.

“Real world wet AMD patients generally lose vision except for those with poor baseline VA,” Ciulla explained. Patients who started with a baseline worse than 20/70 ended up losing by 24 months.

Compared to clinical trials, VA outcomes are worse and there are fewer injections done in the real world. Ciulla said that patients lost to follow-up are likely doing poorly.

The Horizon study was a clinical trial that showed over four years, there was an average two-letter gain. However, this trial was missing 32% of data. “If there was a way to account for this data, the outcomes would have been worse,” Ciulla said, noting that he was a researcher on the study. The CATT study was another example of one that showed substantial results — a three-letter loss after five years – but it was missing 42% of data.

The implication here is that real world outcomes are substantially different than randomized controlled trials. Also, clinicians should know as much information behind a trial as possible before jumping to conclusions — all the while data is missing.

Also on MD Magazine >>> More News from ASRS 2016 in San Francisco