Alemtuzumab Reduces Disability From Relapsing-Remitting Multiple Sclerosis

By Will Boggs MD

NEW YORK (Reuters Health) - Alemtuzumab reduces preexisting disability in patients with active relapsing-remitting multiple sclerosis (RRMS), compared with subcutaneous interferon, according to results from the CARE-MS II study.

"People with MS when treated with alemtuzumab can expect not only to go into long-term remission, but also to have a reasonable chance of reversing some of the disabilities they have acquired from their MS," Dr. Gavin Giovannoni from Queen Mary University of London, Barts and The London School of Medicine, told Reuters Health by email.

In an earlier analysis of CARE-MS II, confirmed disability improvement (CDI), which reflects durable and clinically meaningful changes in Expanded Disability Status Scale (EDSS), was significantly more likely at six months in alemtuzumab-treated patients than in patients treated with subcutaneous interferon-beta-1a.

Dr. Giovannoni and colleagues analyzed disability further using EDSS-based and non-EDSS-based methods in 628 CARE-MS II patients with RRMS with an inadequate response to prior disease-modifying treatments who were randomized to alemtuzumab 12 mg (n=426) or subcutaneous interferon-beta-1a 44 mcg (IFN-beta-1a; n=202).

During 24 months of observation, alemtuzumab patients were significantly more likely than IFN-beta-1a patients to show improvements in EDSS, with statistically significant improvements in five of seven domains: cerebral, cerebellar, sensory, pyramidal, and visual.

Significantly more alemtuzumab patients (34.7%) than IFN-beta-1a patients (19.4%) experienced CDI, and alemtuzumab showed beneficial effects over IFN-beta-1a in integrated disability scores, the researchers report in Neurology, online October 12.

Moreover, alemtuzumab patients had 80% greater odds of showing confirmed improvement in MS Functional Composite scores and they had more favorable visual outcomes.

"These results are a paradigm shift," Dr. Giovannoni said. "For the first time, the aim of treatment can be improvement in disability outcomes rather simply delaying disability progression."

An accompanying editorial strikes a more cautious note. "The CARE-MS II design may artificially overestimate the benefit of alemtuzumab over IFN-beta-1a, because more than 50% of enrolled patients were previously treated with IFN-beta-1a and the inclusion criteria required presence of relapses while on such therapy, which technically excluded patients who had optimal therapeutic response to IFN-beta-1a," write Dr. Bibiana Bielekova from National Institutes of Health, Bethesda, Maryland, and Dr. Mar Tintore from Universitat Autonoma de Barcelona, Spain.

"Nevertheless, a similar observation was seen in treatment-naive patients with RRMS in the CAMMS223 phase 2 trial," they add.

"Even though cumulative evidence indicates that alemtuzumab is one of the strongest MS-modifying treatments currently available, it is not curative, even when applied as early in the disease process as phase II/III trials of alemtuzumab wisely targeted (i.e., mean age ~33 years; mean disease duration ~2 years; and mean EDSS ~2)," the editorial concludes. "Despite unarguable progress in MS therapeutics, there is still a long road ahead until we can eliminate disease progression for all patients."

Dr. Jan Lycke from Sahlgrenska University Hospital's MS Center, Gothenburg, Sweden, told Reuters Health by email, "Alemtuzumab should be offered to patients that fail first-line treatment (interferon beta, GA, teriflunomide, dimethylfumarate) and also those that present disease activity on second-line treatment (natalizumab, fingolimod). We also use alemtuzumab with highly active disease from onset."

"Start effective therapy early," advised Dr. Lycke, who was not involved in the research. "This will allow regeneration and make improvement possible."

The study was funded by Sanofi Genzyme and Bayer HealthCare Pharmaceuticals. Dr. Giovannoni and several co-authors reported financial ties to the companies. Dr. Lycke has served as scientific advisor to Sanofi Genzyme.

SOURCE: https://bit.ly/2duG2bs and https://bit.ly/2duICOD

Neurology 2016.

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