VIENNA, Austria — Compared with subcutaneous interferon β-1a (IFNB-1a; Rebif/EMD Serono/Pfizer), treatment with alemtuzumab (Lemtrada, Genzyme/Sanofi) improved visual outcomes in treatment-naive patients with relapsing-remitting multiple sclerosis (MS), a new study shows.


Detecting the treatment effect depended on using Sloan low-contrast acuity metrics. Visual deficits in MS include impaired contrast sensitivity and contrast letter acuity.

"Low-contrast acuity allows us to see treatment differences and allows us to better understand the visual difficulties that patients have if we were not to use that type of low-contrast metric...that are not captured by high-contrast acuity charts," Steven Galetta, MD, chairman of the Department of Neurology at New York University Langone Medical Center in New York City, told Medscape Medical News.

Alemtuzumab has been studied in 3 clinical trials in MS and has been shown to significantly reduce relapse rates compared with treatment with IFNB-1a. In a phase 2 trial, alemtuzumab was also associated with significantly greater improvement in visual contrast sensitivity vs IFNB-1a (P = .01).

The European Medicines Agency recently approved the drug, but in the United States, the Food and Drug Administration is still reviewing the company's application.

Low-contrast acuity allows us to see treatment differences and allows us to better understand the visual difficulties that patients have if we were not to use that type of low-contrast metric...that are not captured by high-contrast acuity charts.

Patients had active disease (2 or more attacks within 24 months or 1 or more attack within 12 months), Expanded Disability Status Scale score (EDSS) of 0 to 3, and disease onset less than 5 years earlier. The groups were well matched in terms of age (mean, 33 years), sex, time since initial episode, EDSS score, Multiple Sclerosis Functional Composite (MSFC) score, and number of relapses in the prior year.

Contrast Acuity as Fourth Measure of Disability

The MSFC is a sensitive, composite measure of MS disability. It incorporates measures of ambulation/gait, upper-extremity coordination, and cognition. A positive score indicates that a patient is better than the study population as a whole.

By incorporating Sloan contrast testing as a fourth measure in the composite, MSFC-4 captures visual deficits as an additional dimension of disability, the researchers point out.

"Vision wasn't really captured well by the current disability systems that we use, the Kurtzke scale for instance, and it wasn't incorporated into the Multiple Sclerosis Functional Composite," Dr. Galetta explained. "Yet, half of the brain's circuits are dedicated to vision, and vision is so commonly affected in MS. So we just needed a more sensitive measure for visual dysfunction because patients would complain despite reaching 20/20 [acuity] on the standard black-on-white lettering that their vision was still impaired, their quality of life was still impaired visually."

Simple Way of Testing

When asked to comment on the study, Bruce Sigsbee, MD, MS, from Rockport, Maine, and immediate past president of the American Academy of Neurology, told Medscape Medical News, "The current metrics such as the EDSS...really do not directly measure visual function, and yet we know optic neuritis and other visual symptoms are a common manifestation in MS, and their contrast sensitivity study really showed that this was an effective way but a very simple way of testing visual function and the impact of MS on the visual pathways."

He praised the study for using an active comparator group. "Very often new drugs are compared with placebo, and so you really don't have good comparison across different treatments and you're always wondering is this drug better than something we've been using. And they appear to demonstrate that this does have a statistical benefit beyond using just the interferon alone," he said.

But Dr. Sigsbee cautioned that in choosing a drug, one needs to look at the totality of effects, including untoward effects.
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