Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy

Abstract

Objective: To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348).

Methods: Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included 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).

Results: Most alemtuzumab-treated patients (95.1%) completing CARE-MS I enrolled in the extension; 68.5% received no additional alemtuzumab treatment. ARR remained low in years 3, 4, and 5 (0.19, 0.14, and 0.15). Over years 0-5, 79.7% were free of 6-month CDW; 33.4% achieved 6-month CDI. Most patients (61.7%, 60.2%, and 62.4%) had NEDA in years 3, 4, and 5. Median yearly BVL improved over years 2-4, remaining low in year 5 (years 1-5: -0.59%, -0.25%, -0.19%, -0.15%, and -0.20%). Exposure-adjusted incidence rates of most AEs declined in the extension relative to the core study. Thyroid disorder incidences peaked at year 3 and subsequently declined.

Conclusions: Based on these data, alemtuzumab provides durable efficacy through 5 years in the absence of continuous treatment, with most patients not receiving additional courses.

Clinicaltrialsgov identifier: NCT00530348; NCT00930553.

Classification of evidence: This study provides Class III evidence that alemtuzumab durably improves efficacy outcomes and slows BVL in patients with RRMS.

Figure 1. Patient disposition

Disposition schematic includes patient participation from the core CARE-MS I study through the long-term extension study. DMTs include fingolimod (n = 1), glatiramer acetate (n = 2), interferon β-1a (n = 2), interferon β-1b (n = 3), and natalizumab (n = 1). *The death that occurred in the core study was deemed not 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 in alemtuzumab patients. Results are shown for all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. A post hoc analysis revealed no statistically significant difference between ARRs in individual extension years (years 3, 4, and 5) and the ARR in years 0–2. (B) EDSS score change in alemtuzumab patients over 5 years. Proportion of patients with improved (≥1.0-point decrease), stable (≤0.5-point change), or worsened (≥1.0-point increase) EDSS scores at year 5 compared with core study baseline. EDSS score changes are shown for all patients who received alemtuzumab 12 mg in the core study and enrolled in the extension. (C) Proportion of alemtuzumab 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 all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. (D) Proportion of alemtuzumab patients with NEDA over 5 years. Results are shown for all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. *Baseline percentage of patients Gd-enhancing lesion-free: 54%. ARR = annualized relapse rate; CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CDI = confirmed disability improvement; CDW = confirmed disability worsening; EDSS = Expanded Disability Status Scale; Gd = gadolinium; NEDA = no evidence of disease activity.

Figure 3. Brain volume loss over 5 years in alemtuzumab patients

Median yearly percentage change in BPF is shown for all patients who received alemtuzumab 12 mg in the core CARE-MS I study and then enrolled in the extension. BPF = brain parenchymal fraction; CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis.