Durable Efficacy of Alemtuzumab on Clinical and MRI Outcomes over 6 Years in Care-MS II Patients with Active RRMS with Relapse Between Courses 1 and 2

Friday, May 26, 2017: 2:17 PM
R06 (New Orleans Convention Center)
Barry A Singer, MD , MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis, MO
Simon Broadley, MD , School of Medicine, Gold Coast Campus, Griffith University, Queensland, Australia
Angel Chinea, MD , San Juan Multiple Sclerosis Center, San Juan, PR
Mark S Freedman, MD , University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada
Guillermo Izquierdo, MD , Virgen Macarena University Hospital, Seville, Spain
Jan Lycke, MD , Sahlgrenska University Hospital, Gothenburg, Sweden
Basil Sharrack, MD, PhD , Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
Brian Steingo, MD , Fort Lauderdale Multiple Sclerosis Center, Fort Lauderdale, FL
Heinz Wiendl, MD , University of Munster, Munster, Germany
Sibyl Wray, MD , Hope Neurology Multiple Sclerosis Center, Knoxville, TN
David H Margolin, MD, PhD , Sanofi Genzyme, Cambridge, MA
Sourav Santra, PhD , Cytel, Cambridge, MA
Karthinathan Thangavelu, PhD , Sanofi Genzyme, Cambridge, MA
Aaron Boster, MD , OhioHealth Neurological Physicians, Columbus, OH
on behalf of the CARE-MS II and CAMMS03409 Investigators, n/a , MA

Background: Patients with active relapsing-remitting MS and inadequate response (≥1 relapse) to prior therapy (CARE-MS II; NCT00548405) demonstrated improved clinical/MRI outcomes with alemtuzumab versus SC IFNB-1a that were durable through 6 years (NCT00930553). 76% of alemtuzumab-treated patients were relapse-free between Courses 1 and 2; however, some patients relapsed between Courses 1 and 2.

Objectives: Evaluate 6-year efficacy of alemtuzumab in CARE-MS II patients who relapsed between Courses 1 and 2.

Methods: Patients received 2 courses of alemtuzumab 12 mg/day IV (baseline: 5 days; 12 months later: 3 days) in CARE-MS II, and as-needed alemtuzumab for relapse or MRI activity in the extension; another disease-modifying therapy was allowed per investigator discretion. Assessments: annualized relapse rate (ARR); proportions of patients free of 6-month confirmed disability worsening (CDW; Kaplan-Meier estimate), MRI disease activity (gadolinium [Gd]-enhancing T1 and new/enlarging T2 hyperintense lesions), or new T1hypointense lesions; and brain volume loss (BVL) derived by relative change in brain parenchymal fraction.

Results: 105/435 (24%) alemtuzumab-treated patients relapsed in the year following Course 1. Of these, 87/105 (83%) enrolled in the extension; 76/87 (87%) remained on study through Year 6. In patients who relapsed, ARR in Year 1 was 1.2; this declined to 0.5 in the year after Course 2 (40% of this cohort relapsed in Year 2). ARR further declined through Year 6 (Years 3–6: 0.4, 0.4, 0.3, and 0.2, respectively). 60% of patients remained free of 6-month CDW through Year 6, and most were free of Gd-enhancing T1 lesions (94%), new/enlarging T2 hyperintense lesions (68%), MRI disease activity (68%), and new T1hypointense lesions (89%) in Year 6. Median percent yearly BVL decreased over time (Years 1–6: –0.47%, –0.10%, –0.07%, –0.19%, –0.29%, and –0.13%, respectively). 60% of these patients received ≥1 alemtuzumab retreatment.

Conclusions: Outcomes during Year 1 of alemtuzumab do not predict longer-term response, as patients who relapsed in Year 1 improved markedly over the subsequent 5 years. After Course 2, efficacy in this cohort was comparable with overall CARE-MS II alemtuzumab 12 mg population. These findings support administering alemtuzumab according to the approved label (2 courses) to achieve optimal and durable benefits on clinical/MRI outcomes in the small population of patients experiencing relapse between Courses 1 and 2.