Lemtrada aids cognitive skills, eases depression in real-world MS study

One year of treatment with Lemtrada (alemtuzumab) significantly improved cognitive abilities, particularly with processing speed, and eased depression in people with relapsing forms of multiple sclerosis (MS), a small real-world study reported.

Most of the 39 patients (92%) evaluated after that treatment year showed either stable or improved cognitive status. No new safety signals were observed.

The study, “Longitudinal assessment of neurocognitive function in people with relapsing multiple sclerosis initiating alemtuzumab in routine clinical practice: LEM-COG study results,” was published in Multiple Sclerosis and Related Disorders.

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Lemtrada, marketed by Sanofi, is an antibody-based infusion therapy that works by binding to the CD52 protein, which is important for the activation and migration of immune cells that drive MS progression.

The therapy, approved for people with relapsing-remitting MS or active secondary progressive MS, was seen in trials to reduce relapse rates and prevent confirmed disability progression. Less is known about the impact of Lemtrada on cognition in MS patients.

A team of scientists in the U.S. and Canada conducted an observational study, called the LEM-COG study (OBS14527), to examine changes in the cognitive status, as well as measures of depression, fatigue, MRI activity, and safety among people with relapsing forms of MS starting on Lemtrada in routine clinical practice in those two countries.

Its main goal was to assess changes in the patients’ cognition, as measured by an MS Cognitive (MS-COG) composite score, “an extensive, validated, and reliable battery of cognitive testing,” the researchers noted. That score is based on results of four individual cognitive tests measuring processing speed, motor speed, memory, and learning.

Secondary measures included changes in the individual cognitive tests, symptoms of depression in patients, and fatigue severity, as well as changes in lesion volume and number.

The study involved four visits over two years: a screening visit to determine eligibility, a baseline (study start) visit to gather information on cognitive status before using Lemtrada, and two follow-up visits at one and two years later.

A total of 112 patients were enrolled, 89 in the U.S. and 23 in Canada. Of them, 109 people, who had been living with MS for a mean of eight years, received at least one dose of Lemtrada. Their mean age was 40.8 and most were women (72.5%) and white (81.9%).

A total of 107 patients (98.2%) received a full first treatment course — 12 mg doses given daily for five consecutive days (total 60 mg dose) — and 39 had available testing data after one year. Seven patients reached the two-year assessment.

MS-COG scores significantly improved in the 39 people evaluated after one year of treatment, moving from -0.61 to -0.36. Improvements also were observed at two years, but the small number of patients tested made definitive findings impossible.

“About 92% of participants showed stable or improved cognitive status at [one year],” the researchers wrote. More specifically, cognitive abilities were stable after one year of treatment in 61.54% of these patients, and cognitive gains were seen in 30.77%.

Gains in processing speed may drive MS-COG composite score improvements

Processing speed also improved significantly, by a mean of 0.33 points from baseline to the one-year follow-up. Processing speed for MS-COG was based on the Paced Auditory Serial Addition Test (PASAT) and the Symbol Digit Modalities Test (SDMT).

In the PASAT, a patient listens to a series of numbers and adds each in the series to the number just before it; with SDMT, the patient is asked to match symbols to numbers as quickly as possible. Scores on each individual cognitive test also improved significantly, though other measures of cognition showed no significant changes.

These findings suggest that “improvement in MS-COG seems to be driven by improvement in processing speed,” the researchers wrote.

While no changes were noted in fatigue, Lemtrada’s use led to a significant easing of depression, as seen in changes on Hamilton Rating Scale for Depression scores at one year. There was also a significant decrease in lesion burden and in the number of new lesions with active inflammation.

Lemtrada’s safety profile was consistent with previous studies. The most common side effects were headache, fatigue, nausea, insomnia, urinary tract infection, and pain in the extremities.

“The findings from this study suggest that [Lemtrada] has a positive impact on cognitive function with significant improvements in processing speed and depression in people with [relapsing MS] over a period of 12 months,” the researchers concluded.

Four of the study’s 12 scientists are — or were at the time of this work — Sanofi employees, and the company funded the study.