Durable Improvements in MRI Disease Activity and Brain Volume Loss with Alemtuzumab in RRMS Patients: 7-Year Follow-up of Care-MS II

Friday, June 1, 2018: 2:17 PM
209 (Nashville Music City Center)
Daniel Pelletier, MD , Keck School of Medicine of University of Southern California, Los Angeles, CA
Anthony Traboulsee, MD , University of British Columbia, Vancouver, BC, Canada
Michael Barnett, PhD, MD , University of Sydney, Sydney, NSW, Australia
Giancarlo Comi, MD , University Vita-Salute San Raffaele, Milan, Italy
Jerome de Seze, MD PhD , University Hospital of Strasbourg, Strasbourg, France
Alex Rovira, MD , Vall d'Hebron University Hospital, Barcelona, Spain
Sven Schippling, MD , Neuroimmunology and Multiple Sclerosis Research, University Hospital Zurich and University of Zurich, Zurich, Switzerland
Luke Chung, MD, MPH , Sanofi, Cambridge, MA
Nadia Daizadeh, PhD , Sanofi, Cambridge, MA
Kunio Nakamura, PhD , Cleveland Clinic, Cleveland, OH
Douglas L Arnold, MD , Montreal Neurological Institute, McGill University, Montreal, QC, Canada
on behalf of the CARE-MS II, CAMMS03409, and TOPAZ, Investigators , on behalf of the CARE-MS II, CAMMS03409, and TOPAZ Investigators, NJ

Background: In CARE-MS II (NCT00548405), alemtuzumab (12 mg/day, baseline: 5 days; 12 months later: 3 days) significantly improved MRI outcomes, including brain volume loss (BVL) versus SC IFNB-1a over 2 years (y) in RRMS patients with an inadequate response to prior therapy at baseline. Durable efficacy was observed in a 4-y extension (NCT00930553; 393/423 [93%] CARE-MS II patients enrolled, 338 [86%] completed), in which patients could receive alemtuzumab retreatment as needed for relapse/MRI activity or receive other disease-modifying therapies (DMTs) per investigator’s discretion. Patients completing the extension could enroll in TOPAZ, a 5-y study (NCT02255656), for further evaluation.

Objectives: To evaluate MRI lesion outcomes and BVL over 7 y (2 y of core study plus 4 y of extension and Y1 of TOPAZ) in RRMS patients initially randomized to alemtuzumab in CARE-MS II.

Methods: In TOPAZ, patients can receive alemtuzumab (12 mg/day on 3 consecutive days) retreatment ≥12 months after the most recent course or other DMTs at any time, both per investigator’s discretion. Assessments: Annual MRI for disease activity (scored as new gadolinium [Gd]-enhancing lesions; new/enlarging T2 lesions), new T1 hypointense lesions, and BVL (derived by relative change in brain parenchymal fraction [BPF]).

Results: Of the 336 patients who entered TOPAZ, 317 (94%) completed Y1 (Y7 after initiating alemtuzumab). 47% received neither alemtuzumab retreatment nor another DMT, and 88% did not receive another DMT after the initial 2 courses. At Y7, patients were free of MRI disease activity (67%), new Gd-enhancing lesions (90%), new/enlarging T2 lesions (67%), and new T1 hypointense lesions (88%). Median change from baseline in BPF was –0.48%, –0.62%, –0.69%, –0.88%, –0.86%, –0.96%, and –0.94% in Y1–7, respectively. Median annual BPF change was significantly reduced with alemtuzumab versus SC IFNB-1a over 2 y (Y1: –0.48% vs –0.54%, Y2: –0.62% vs –0.81%; P=0.0121 vs SC IFNB-1a in Y2), remaining low in alemtuzumab-treated patients in Y3–7 (Y3: –0.10%, Y4: –0.19%, Y5: –0.07%, Y6: –0.10%, Y7: –0.14%). 

Conclusions: Alemtuzumab durably reduced MRI disease activity and slowed BVL over 7 y in patients who were initially randomized to alemtuzumab in CARE-MS II, despite 47% receiving no additional treatment after the initial 2 courses. Alemtuzumab provides a unique treatment approach for RRMS patients, offering durable efficacy without continuous treatment.

Study Support: Sanofi and Bayer HealthCare Pharmaceuticals.