Efficacy of a Fourth Alemtuzumab Course in RRMS Patients with Disease Activity after Three Prior Courses: Analysis of Care-MS II

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
Barry A Singer, MD , MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis, MO
Raed Alroughani, MD , Amiri Hospital, Sharq, Kuwait
Aaron Boster, MD , OhioHealth Neurological Physicians, Columbus, OH
Ann D. Bass, MD , Neurology Center of San Antonio, San Antonio, TX
Regina Berkovich, MD, PhD , University of Southern California, Keck School of Medicine, Los Angeles, CA
Giancarlo Comi, MD , University Vita-Salute San Raffaele, Milan, Italy
Oscar Fernandez, MD , Fundacion IMABIS, Hospital Universitario Carlos Haya, Malaga, Spain
Ho Jin Kim, MD , Research Institute and Hospital of National Cancer Center, Goyang, Korea, Republic of (South)
Volker Limmroth, MD, PhD , Klinik fur Neurologie und Palliativmedizin, Cologne, Germany
Jan Lycke, MD , Sahlgrenska University Hospital, Gothenburg, Sweden
Richard AL Macdonell, MD , Austin Health and Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
Basil Sharrack, MD, PhD , Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
Patrick Vermersch, MD , University of Lille, Lille, France
Heinz Wiendl, MD , University of Munster, Munster, Germany
Tjalf Ziemssen, MD, PhD , Carl Gustav Carus University Hospital, Dresden, Germany
Maria Melanson, MD, PhD , Sanofi, Cambridge, MA
Nadia Daizadeh, PhD , Sanofi, Cambridge, MA
Anthony Traboulsee, MD , University of British Columbia, Vancouver, BC, Canada
on behalf of the CARE-MS II and CAMMS03409, Investigators , on behalf of the CARE-MS II and CAMMS03409 Investigators, NJ

Background: In the CARE-MS II core study (NCT00548405), alemtuzumab 12 mg/day significantly improved clinical and MRI outcomes versus SC IFNB-1a over 2 years in patients with RRMS and an inadequate response to prior therapy at baseline. In the core study, patients received 2 courses of alemtuzumab, which were administered 12 months apart (baseline: 5 days; 12 months later: 3 days). In a 4-year extension study (NCT00930553), patients could receive as-needed alemtuzumab retreatment (12 mg/day, 3 consecutive days; ≥12 months apart) for relapse and/or MRI activity, or another disease-modifying therapy (DMT) per investigator’s discretion. Efficacy remained durable, despite 50% of patients receiving neither alemtuzumab retreatment nor another DMT. Through Year 6, 344 of the 393 (88%) patients who entered the extension remained on study; 62 (16%) received ≥4 alemtuzumab courses (49 [12%] received exactly 4 courses), and 13 (3%) received ≥5 courses.

Objectives: To evaluate efficacy of a fourth course of alemtuzumab (Course [C] 4) in CARE-MS II patients who received ≥4 courses due to relapse and/or MRI activity.

Methods: Assessments 12 months before and up to 3 years after alemtuzumab C4 were compared: annualized relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus core study baseline); 6-month confirmed disability improvement (CDI). Included patients (N=43 [11%]) received ≥4 courses within 60 months of baseline to allow for 1 year of follow-up after C4, and received no other DMT. Data for those who received a fifth course (C5) were censored at the time of C5 administration onward.

Results: ARR decreased following treatment with C4, from 0.75 (12 months before C4) to 0.19 (12 months after C4; rate ratio [95% CI], 0.25 [0.13–0.49]; P<0.0001), remaining low (0.23) at Year 3 after C4. EDSS scores versus core study baseline were stable/improved in 67.5% of patients 12 months after C4, compared with 53.5% of patients at the time of C4 administration. The percentage with CDI increased from 10.0% (12 months before C4) to 26.7% (12 months after C4). Outcomes were similar among the subgroup of patients who received exactly 4 courses, as in those who received ≥4 courses.

Conclusions: A fourth course reduced relapses and stabilized/improved disability in CARE-MS II patients who received ≥4 courses due to disease activity after 3 prior alemtuzumab courses.

Study Support: Sanofi and Bayer HealthCare Pharmaceuticals.