Alemtuzumab CARE-MS II 5-year follow-up

Abstract

Objective:To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy.Methods:In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. Annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs) were assessed.Results:Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3–5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1–5: −0.48%, −0.22%, −0.10%, −0.19%, −0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter.Conclusions:Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment.Classification of evidence:This study provides Class III evidence that alemtuzumab provides efficacy and slowing of brain atrophy through 5 years.

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options

“…Extension studies showed sustained low brain atrophy rates, in the absence of continuous treatment with Alemtuzumab or other DMTs during the follow up period [149]. The CARE-MS II 5-year follow-up study (2017) provided class III evidence that Alemtuzumab slows brain atrophy; the annual BVL rate continued to drop during the third year and remained low through the fourth and fifth year as well [150].…”

Passive Monoclonal and Polyclonal Antibody Therapies

“…Alemtuzumab (Lemtrada) is a humanized Mab (IgG1k) targeting CD52 that depletes lymphocytes (B and T cell) as reported earlier and is FDA approved for treatment of acute relapsing and remitting multiple sclerosis. 292 Ocrelizumab (Ocrevus) is a humanized Mab (IgG1k) with specificity to CD20 (a B-cell membrane protein). In phase II trials, there were decreases in brain lesions on imaging, and decrease rate of disability decline in primary progressive multiple sclerosis.…”

Disease-Modification in Huntington’s Disease: Moving Away from a Single-Target Approach

“…While this latter concept of disease subtypes is currently poorly understood, it is clear that patients do follow different courses and some of the genetic basis for this is being identified, both in HD [65], and in other neurodegenerative disorders such as Parkinson's disease [66]. However disease stage has long been argued to be important in the use of disease-modifying drugs in neurology, for example in Alzheimer's disease [67] and multiple sclerosis [68,69]. So in HD, could low clinical success rates be explained, in part, by failure to initiate therapy early?…”