The use of alemtuzumab in patients with relapsing-remitting multiple sclerosis (RRMS) was found to be associated with clinical and magnetic resonance imaging (MRI) disease remission, along with improvements in disability, according to the results of a retrospective, multicenter, real-world study conducted in Italy. Findings from the analysis were published in the Journal of Neurology.
Investigators collected clinical and MRI data from 40 patients with RRMS who were treated with alemtuzumab according to a “free-of-charge” protocol that was available before the marketing approval of the drug in Italy. Almost all of the patients (39 of 40) initiated treatment with the agent after the discontinuation of multiple disease-modifying treatments (DMTs) because of lack of response or safety concerns.
The primary study outcome was the percentage of patients who achieved no evidence of disease activity (NEDA-3) status, which is a combined measure defined as the absence of clinical response, confirmed disability worsening, and MRI activity. Secondary outcomes included each subcomponent of disease activity (ie, clinical relapses, confirmed disability worsening, and MRI activity). The tertiary outcome was the occurrence of sustained disability improvement. Disability improvement was defined as a sustained decrease of ≥1 point in the Expanded Disability Status Scale (EDSS) score. A relapse was defined as any new neurologic symptom that was not associated with fever or infection, lasted for ≥24 hours, and was accompanied by new neurologic signs.
Alemtuzumab was administered over 2 treatment courses as an intravenous infusion of
12 mg/d on 5 consecutive days (first course) and then, 12 months later, 12 mg/d on 3 consecutive days (second course).
At 3-year follow-up, 45% (18 of 40) of patients achieved NEDA-3, 75% (30 of 40) were free of relapse, 82.5% (33 of 40) demonstrated no worsening of EDSS, and 62.5% (25 of 40) had no evidence of MRI activity. Overall, 27.5% (11 of 40) of participants experienced sustained disability improvement.
No baseline factor (eg, sex, age, time since first symptom, EDSS score, number of relapses in the prior year, number of gadolinium-enhancing lesions, number of DMTs taken before alemtuzumab, time from last DMT discontinuation to initial alemtuzumab administration) was shown to be associated with a higher or lower possibility of achieving NEDA-3 status.
The interaction of higher EDSS score by higher number of relapses in the pre-alemtuzumab year, however, was linked to a significantly higher likelihood of disability improvement (odds ratio, 1.10; 95% CI, 1.00-1.22; P =.049). Moreover, a fair concordance between NEDA-3 and disability improvement was observed (P =.047), implying that the occurrence of some disease activity did not necessarily prevent the reduction in disability reported after treatment with alemtuzumab.
The investigators concluded that this study provides real-world evidence that alemtuzumab therapy can promote clinical and MRI disease remission, along with disability improvement, in a significant percentage of patients with RRMS despite prior multiple DMT failures. The drug safety profile of alemtuzumab was consistent with data from prior clinical trials.
Prosperini L, Annovazzi P, Boffa L, et al; on behalf of the Italian Alemtuzumab Study Group. No evidence of disease activity (NEDA-3) and disability improvement after alemtuzumab treatment for multiple sclerosis: a 36-month real-world study. J Neurol. 2018;265(12):2851-2860.