PT  - JOURNAL ARTICLE
AU  - Coles, Alasdair J.
AU  - Cohen, Jeffrey A.
AU  - Fox, Edward J.
AU  - Giovannoni, Gavin
AU  - Hartung, Hans-Peter
AU  - Havrdova, Eva
AU  - Schippling, Sven
AU  - Selmaj, Krzysztof W.
AU  - Traboulsee, Anthony
AU  - Compston, D. Alastair S.
AU  - Margolin, David H.
AU  - Thangavelu, Karthinathan
AU  - Chirieac, Madalina C.
AU  - Jody, Darlene
AU  - Xenopoulos, Panos
AU  - Hogan, Richard J.
AU  - Panzara, Michael A.
AU  - Arnold, Douglas L.
ED  - , 
TI  - Alemtuzumab CARE-MS II 5-year follow-up
AID  - 10.1212/WNL.0000000000004354
DP  - 2017 Sep 12
TA  - Neurology
PG  - 1117--1126
VI  - 89
IP  - 11
4099  - http://n.neurology.org/content/89/11/1117.short
4100  - http://n.neurology.org/content/89/11/1117.full
SO  - Neurology2017 Sep 12; 89
AB  - 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.AE=adverse event; ARR=annualized relapse rate; BPF=brain parenchymal fraction; BVL=brain volume loss; CARE-MS II=Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis II; CDI=confirmed disability improvement; CDW=confirmed disability worsening; CI=confidence interval; DMT=disease-modifying therapy; EAIR=exposure-adjusted incidence rate; EDSS=Expanded Disability Status Scale; Gd=gadolinium; IAR=infusion-associated reaction; IFN-β-1a=interferon β-1a; ITP=immune thrombocytopenia; MS=multiple sclerosis; NEDA=no evidence of disease activity; RRMS=relapsing-remitting multiple sclerosis; SC=subcutaneous