Slowing disability in multiple sclerosis (MS) is an important measure of therapeutic efficacy of disease-modifying therapies (DMTs). Recent studies are assessing the ability of DMTs to modify disability measures in addition to slowing it down. The restoration of function in patients with MS has important implications, including improved long-term prognosis, greater quality of life, and reduced economic costs. A recent study investigated the effects of alemtuzumab (Lemtrada) on disability measures in patients with MS (Giovannoni G, et al. Neurology. 2016;87:1985-1992).
The 2-year, randomized, active controlled, head-to-head, phase 3 clinical trial CARE-MS II compared the efficacy and safety of alemtuzumab with that of interferon beta-1 (Rebif) in patients with relapsing-remitting MS (RRMS) with inadequate response to previous DMTs. The study demonstrated that confirmed disability improvement was more likely with alemtuzumab than with interferon beta-1. In addition, alemtuzumab was associated with greater mean Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores.
To better characterize the effects of alemtuzumab on disability in patients with RRMS, Gavin Giovannoni, MD, PhD, of Queen Mary University of London, England, and colleagues conducted post hoc analyses of the CARE-MS II study.
“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 impairments, and there is a corresponding need for suitable metrics and analytic methods to reflect this novel outcome,” wrote Dr Giovannoni and colleagues.
The analyses focused on the improvement of preexisting disability and the slowing of disability accumulation. Disability was assessed with EDSS-based and non–EDSS-based methods, MSFC scores, and Sloan low-contrast letter acuity (SLCLA) scores.
From baseline to month 24, patients who received alemtuzumab were more likely to show improvements in EDSS scores versus patients who received interferon beta-1. In addition, the odds of improvement in 7 EDSS functional systems, including cerebral, cerebellar, sensory, pyramidal, visual, brainstem, and bowel/bladder, were greater with alemtuzumab compared with interferon beta-1 (P <.0001), suggesting that such disabilities may often be reversible in patients with active RRMS if they receive appropriate therapy.
Furthermore, the 6-month disability improvement and MSFC scores remained consistently better with alemtuzumab than with interferon beta-1.
Patients who received alemtuzumab had more favorable visual outcomes than those who received interferon beta-1; visual acuity in patients who received alemtuzumab was stable at 2.5% contrast and at 100% contrast. When assessing disability progression in MS, sensitivity to change can be enhanced by combining different outcome measures. In this study, the MSFC scores plus the SLCLA scores from baseline to 12 months significantly improved with alemtuzumab versus interferon beta-1 (0.04; P = .0396).
“The outcomes presented here not only support alemtuzumab’s ability to slow disability accumulation, but also demonstrate superior benefit in improving preexisting disability in patients with RRMS with an inadequate response to prior DMT,” Dr Giovannoni and colleagues observed.
Although the mechanisms responsible for improving preexisting disability are not yet elucidated, the researchers suggest that alemtuzumab’s effective inhibition of central nervous system inflammation may provide a tissue environment that is conducive to remyelination and repair mechanisms. They further hypothesize that neurotrophic factors, thought to contribute to neuroprotection, may also play a role in repairing and restoring disability in patients with MS.
“These data add to the body of evidence supporting a favorable benefit-risk profile of alemtuzumab in the treatment of RRMS,” Dr Giovannoni and colleagues concluded.