Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients

Abstract

Objective:To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy.Methods:Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation.Results:Alemtuzumab-treated patients were more likely than SC IFN-β-1a–treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a–treated patients.Conclusions:In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities.Classification of evidence:This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a.

Alemtuzumab: a review of efficacy and risks in the treatment of relapsing remitting multiple sclerosis

“…This analysis showed improvement in the Multiple Sclerosis Functional Composite (MFSC) score, mostly on arm function [9-Hole Peg Test (9-HPT)], and in the Sloan low contrast letter acuity (SLCLA) score. In addition, about half of the patients treated with alemtuzumab had an improvement in EDSS scores ( P <0.0001) in all the 7 EDSS functional domains 10. Moreover, data from follow-up and extension studies of patients from Phase II and Phase III trials reproduced results previously obtained on relapse rate and disability.…”

Minimal evidence of disease activity (MEDA) in relapsing-remitting multiple sclerosis

“…All models were stratified by site and adjusted by calendar year at treatment start and baseline variables (covariates of no interest). Exposure to highly intensive treatments was also inserted in the models as time-varying covariate, under the assumption that escalation to intravenous immunosuppressants (mitoxantrone, cyclophosphamide) and monoclonal antibodies (natalizumab, alemtuzumab, ocrelizumab, rituximab) may have affected the patients’ disability status during the follow-up 14–16. To assess robustness of the results, a post-estimation sensitivity analysis was done by re-running all models after removing patients who were escalated to highly intensive treatments.…”

Disease-modifying therapies for multiple sclerosis

“…DMTs generally do not improve established symptoms of multiple sclerosis, though preliminary evidence suggests some improvement in disability with alemtuzumab and natalizumab 2930. Observational studies report conflicting evidence on the impact of interferon beta in reducing long term disability and development of secondary progressive multiple sclerosis 3132…”