Proportion of alemtuzumab-treated patients converting from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis over 6 years

Abstract

Background: Few data exist concerning conversion to secondary progressive MS in patients treated with disease-modifying therapies.

Objective: Determine the proportion of alemtuzumab-treated patients converting from relapsing-remitting to secondary progressive MS during the CARE-MS core and extension studies.

Methods: Patients (N = 811) were analyzed post hoc for secondary progressive MS conversion. Optimal conversion definition: Expanded Disability Status Scale (EDSS) score ≥4, pyramidal functional system score ≥2, and confirmed progression over ≥3 months including confirmation within the functional system leading to progression, independent of relapse.

Results: Over 6.2 years median follow-up, 20 alemtuzumab-treated patients converted (Kaplan-Meier estimate, 2.7%; 95% confidence interval, 1.8%-4.2%). Sensitivity analysis accounting for dropouts showed similar results (3%), as did analyses using alternative definitions with different EDSS thresholds and/or confirmation periods, and analysis of core study subcutaneous interferon beta-1a-treated patients who received alemtuzumab in the extension. Patients converting to secondary progressive MS were older, and had higher EDSS scores and greater brain lesion volumes at baseline, but did not need additional alemtuzumab or other therapies.

Conclusions: The 6-year conversion rate to secondary progressive MS was low for alemtuzumab-treated patients, supporting further study of the role alemtuzumab may play in reducing risk of secondary progression.ClinicalTrials.gov identifiers: NCT00530348, NCT00548405, NCT00930553.

Keywords: Relapsing-remitting multiple sclerosis; alemtuzumab; disease progression; secondary progressive multiple sclerosis.

Figure 1.

Patient disposition in the CARE-MS core and extension studies. Abbreviations: CARE-MS, Comparison of Alemtuzumab and Rebif^® Efficacy in Multiple Sclerosis. ^aDeemed unrelated to alemtuzumab treatment (3 deaths). ^bDeemed unrelated (1 death) and possibly related (2 deaths) to alemtuzumab treatment. ^cDeemed unrelated to alemtuzumab treatment (1 death) and relationship to alemtuzumab treatment unable to be determined (1 death).

Figure 2.

Kaplan-Meier estimate of secondary progressive MS conversion in the pooled CARE-MS alemtuzumab-only population (EDSS threshold ≥4; different confirmation periods). Abbreviations: CARE-MS, Comparison of Alemtuzumab and Rebif^® Efficacy in Multiple Sclerosis; EDSS, Expanded Disability Status Scale. No patients converted to secondary progressive MS when a confirmation period of 24 months was used.