Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings

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.

Figure 1. Patient disposition

The disposition schematic includes participation of patients treated with alemtuzumab 12 mg in the core CARE-MS II and then enrolled in the long-term extension study. *The as-treated population (n = 435) consisted of 426 patients originally randomized to alemtuzumab 12 mg and an additional 9 patients who were randomized to alemtuzumab 24 mg but who instead received alemtuzumab 12 mg/d in the core study. **Neither death that occurred in the core study was related to treatment. CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; DMT = disease-modifying therapy.

Figure 2. Clinical efficacy and disease activity outcomes over 5 years in alemtuzumab patients

(A) ARR over 5 years. Results are shown for patients who received alemtuzumab 12 mg in the core CARE-MS II study and enrolled in the extension. A post hoc analysis revealed a statistically significant difference between the ARR in year 5 and the ARR in years 0–2 (p = 0.0021), and no significant difference between ARRs in either year 3 or year 4 and the ARR in years 0–2. (B) Percentage of patients with improved (≥1.0-point decrease), stable (≤0.5-point change), or worsened (≥1.0-point increase) EDSS scores at year 5 of the extension study compared with core study baseline. Analyses are shown for all patients who received alemtuzumab 12 mg in the core study and enrolled in the extension. (C) Percentage of patients with 3-, 6-, or 12-month CDI over 5 years. Kaplan-Meier analysis of time to 3-, 6-, or 12-month CDI is shown for patients who received alemtuzumab 12 mg in the core CARE-MS II study and enrolled in the extension. (D) Proportion of patients with NEDA over 5 years. NEDA outcomes are shown for patients who received alemtuzumab 12 mg in the core CARE-MS II study and enrolled in the extension. *Baseline percentage of patients free of gadolinium (Gd)–enhancing lesions: 58%. ARR = annualized relapse rate; CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CDI = confirmed disability improvement; CDW = confirmed disability worsening; CI = confidence interval; EDSS = Expanded Disability Status Scale; NEDA = no evidence of disease activity.

Figure 3. Brain volume loss over 5 years

Median percentage yearly change in brain parenchymal fraction (BPF). Results are shown for patients who received alemtuzumab 12 mg in the core study and enrolled in the extension. CI = confidence interval.