Alemtuzumab (Lemtrada®), typically used to treat late-stage relapsing-remitting multiple sclerosis (RRMS), may also help to improve physical disability in patients with RRMS who failed to respond to 1 previous disease-modifying treatment (DMT).
The data, a secondary analysis of the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II trial (NCT00548405), was published in Neurology.1 In this analysis, the authors aimed to identify confirmed disability improvement (CDI), defined as a “higher standard of therapeutic efficacy than merely slowing disability accumulation” that reflects a clinically meaningful change in Expanded Disability Status Scale (EDSS) score. In order to get a more complete picture of the effects of alemtuzumab, the analysis also included non-EDSS methods.
The trial included 426 and 202 patients with RRMS randomized to receive either alemtuzumab (12 mg) or subcutaneous interferon-β-1a (44 µg).2,3 Patients who had an inadequate response to a prior DMT, defined as ≥1 relapse while receiving treatment with interferon-β or glatiramer acetate for ≥6 months, were included in the study.
At 2 years, patients treated with alemtuzumab were more likely to show improvements in EDSS, with statistically significant changes occurring in 5 domains: cerebral, cerebellar, sensory, pyramidal, and visual. Patients receiving alemtuzumab were also more than twice as likely to experience 3-month CDI compared to patients receiving interferon-β-1a (34.7% vs 19.4%, P= .0003 [HR= 2.13]).
Alemtuzumab was found to be beneficial, as indicated by its effects on the integrated disability score AUCCHANGE (mean [SD] -2.3 [18.45] vs 2.9 [16.84]; P= .0016) and AUCSUM analysis (62.8 [31.02] vs 64.8 [32.27]; P= .0114).
More patients without recent pre-treatment relapse experienced 3- and 6-month CDI when treated with alemtuzumab compared with interferon-β-1a over 2 years (33.8% vs 15.2%, P= .0004; 28.8% vs 9.2%, P= .0002).
As for the Multiple Sclerosis Functional Composite (MSFC) component, the greatest benefit at 24 months was seen for the 9-Hole Peg Test, a measurement of upper limb coordination, in patients receiving alemtuzumab vs interferon-β-1a (P= .0007). Non-significant improvements in visual acuity were observed in patients receiving alemtuzumab at 12 and 24 months, while a significant decline was measured in patients receiving interferon-β-1a (1.25% contrast [month 12: -0.25; month 24: -0.19; both P< .01]; 2.5% contrast [month 12: -0.20; month 24: -0.21; both P< .001]; and 100% contrast [month 24: -0.16; P= .0105]).
“The current analysis demonstrates that, in patients with RRMS with an inadequate response to prior DMTs, alemtuzumab provides greater recovery of function across several disability measures than SC IFN-b-1a,” the authors concluded. “The use of this active comparator in the CARE-MS studies set a high threshold for superiority compared with placebo-controlled studies of other DMTs.”
The results suggest that disabilities – even those present at baseline – may be reversible in patients treated with an adequate DMT. While the mechanisms underlying the beneficial effects of alemtuzumab in patients are not completely understood, the researchers hypothesized that the compound, by reducing central nervous system inflammation, may provide a more suitable environment for remyelination and repair mechanisms.
“One can only speculate whether the sustained reduction in disability (SRD) is due to structural repair (ie, remyelination) or functional repair (ie, plasticity, such as formation of new synapses),” wrote Bibiana Bielekova, MD and Mar Tintore, MD, of the National Institute of Neurological Disorders and Stroke and the Universitat Autònoma de Barcelona, Spain, respectively, in a related editorial.4 “Indeed, if SRD is caused by plasticity, it should not be observed in patients with more advanced disability, where the extent of CNS tissue destruction precludes functional recovery because of the lack of neuronal reserves.”
The authors noted that an authentic double-blind study design was not feasible given differences in timing, mode of administration, and side effect profiles of the drugs, and that the benefits of alemtuzumab over interferon-β-1a should be weighed against the known risks of alemtuzumab treatment, including infusion reactions, infection, and autoimmune adverse events.3,5
Disclosures: The study was funded by Sanofi Genzyme, which manufactures the drug, and Bayer HealthCare Pharmaceuticals. The study authors report several disclosures. See the study for the full listing.
- Giovannoni G, Cohen JA, Hartung HP, et al. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients. Neurology. 2016;87:1–8.
- Coles AJ, Fox E, Vladic A, et al. Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol. 2011;10:338–348.
- Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after diseasemodifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380:1829–1839.
- Bielekova B, Tintore M. Sustained reduction of MS disability: New player in comparing disease-modifying treatments. Neurology. 2016;87:1–2.Menge T, Stüve O, Kieseier BC, Hartung HP. Alemtuzumab: the advantages and challenges of a novel therapy in MS. Neurology. 2014;83:87–97.