medwireNews: Alemtuzumab improves pre-existing disability in multiple sclerosis (MS) patients rather than just slowing its progression, shows analysis of the CARE-MS II trial.
“Current treatments may delay or prevent further increases in disability. However, few data exist concerning the ability of current treatments to help restore function over time in patients with previously acquired neurologic impairment”, say Gavin Giovannoni (Queen Mary University of London, UK) and team.
The trial involved 628 patients with relapsing–remitting MS who had failed to respond adequately to previous disease-modifying therapies.
Outcomes assessed at the start of treatment and again every 3 months showed that nearly 28% of the 426 patients randomly assigned to receive alemtuzumab 12 mg/day showed clinical improvement of at least 1 point on the Expanded Disability Status Scale (EDSS) at 2 years. This compared with 15% of the 202 patients treated with 44 µg subcutaneous interferon (IFN)-β-1a three times a week.
By contrast, worsening of EDSS symptoms was seen in about 24% and 40% of patients, respectively.
The researchers note in Neurology that the odds of improvement increased with alemtuzumab treatment across all seven systems of the EDSS and reached significance in five domains: cerebral (odds ratio [OR]=2.54); cerebellar (OR=2.26); sensory (OR=1.88); pyramidal (OR=1.62) and visual (OR=1.59).
Commenting on this finding in a related editorial, Bibiana Bielekova (National Institutes of Health, Bethesda, Maryland, USA) and Mar Tintore (Universitat Autònoma de Barcelona, Spain) point out: “This consistency across multiple domains supports clinical relevance of [sustained reduction in disability] as an outcome measure.”
Such a sustained reduction in disability was seen in twice as many patients treated with alemtuzumab as with IFN-β-1a at 3 months, at 34.7% versus 19.4%. And similar findings were seen at 6 months, including for those with an EDSS score of 3 or above.
The researchers note that their findings did not merely reflect disability improvement due to recovery from recent relapse, as 6-month improvement was comparable for alemtuzumab patients who did and did not relapse in the first 3 months.
Noting that EDSS is “heavily weighted toward ambulation and relatively insensitive to other aspects of disability”, the researchers also assessed scores on the Multiple Sclerosis Functional Composite (MSFC) and the Sloan low-contrast letter acuity (SLCLA) scales.
Patients taking alemtuzumab were 80% more likely than those given IFN-β-1a to have confirmed improvements (increase of at least 0.5 points) on the MSFC at 6 months, primarily in limb coordination and dexterity, while IFN-β-1a-treated patients were significantly more likely to experience MSFC worsening of at least 15% on at least one component (27.58 vs 18.66%).
Changes on the SLCLA were also more favourable with alemtuzumab than IFN-β-1a treatment at 2.5% contrast and for MSFC and SLCLA composite scores.
Giovannoni and team say that, collectively, their findings for alemtuzumab reflect “an important, clinically meaningful benefit beyond slowing or preventing neurologic deterioration”.
But they caution that the disability benefits “should be considered in the context of the risks, including infusion-associated reactions, infections, and autoimmune adverse events”.
They say: “Measures to manage these potentially serious risks are essential for the safe use of alemtuzumab.”
By Lucy Piper
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