Number Needed to Treat Analyses Comparing Outcomes in Patients with Relapsing-Remitting Multiple Sclerosis Treated with Alemtuzumab or Ocrelizumab

Thursday, May 25, 2017
B2 (New Orleans Convention Center)
Aaron Boster, MD , OhioHealth Neurological Physicians, Columbus, OH
Raed Alroughani, MD , Amiri Hospital, Sharq, Kuwait
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
Guillermo Izquierdo, MD , Virgen Macarena University Hospital, Seville, Spain
Daniel Kantor, MD , Kantor Neurology, Coconut Creek, FL
Christopher LaGanke, MD , North Central Neurology Associates, Cullman, AL
Richard AL Macdonell, MD, FRACP , Brain Research Institute, Florey Institute of Neuroscience and Mental Health, Melbourne, Australia
Thibault Moreau, MD , University of Burgundy, Dijon, France
Basil Sharrack, MD, PhD , Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
Heinz Wiendl, MD , University of Munster, Munster, Germany
Bart Van Wijmeersch, MD, PhD , Rehabilitation & MS-Centre Overpelt, BIOMED, Hasselt University, Hasselt, Belgium
David H Margolin, MD, PhD , Sanofi Genzyme, Cambridge, MA
Karthinathan Thangavelu, PhD , Sanofi Genzyme, Cambridge, MA
Maria Melanson, MD, PhD , Sanofi Genzyme, Cambridge, MA
Mark S Freedman, MD , 1University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, Canada

Background: In the absence of head-to-head trials, the number needed to treat (NNT) can be used to indirectly assess comparative efficacy of disease-modifying therapies. 

Objectives: Analyze the NNT to prevent clinical disease events in studies of alemtuzumab and ocrelizumab in relapsing-remitting MS. 

Methods: NNT values were derived from post hoc analyses of 2-year data from studies of alemtuzumab 12 mg and ocrelizumab 600 mg. Alemtuzumab data were pooled treatment-naive patients from CAMMS223 and CARE-MS I (NCT00050778 and NCT00530348, N=786), and separately, patients with inadequate response to prior therapy from CARE-MS II (NCT00548405, N=628). Ocrelizumab data were individual OPERA I and II studies (NCT01247324, N=821; NCT01412333, N=835). Alemtuzumab was administered as 2 annual courses (baseline: 5 days; 12 months later: 3 days); ocrelizumab was administered at baseline and Weeks 24, 48, 72. NNT was based on inverse of absolute risk differences versus SC IFNB-1a 44 µg 3×/week (common comparator) for annualized relapse rate (ARR) and proportion of patients experiencing relapse, and the Altman method for 6-month confirmed disability worsening (CDW). Lower NNT values reflect greater efficacy.

Results: Baseline mean EDSS scores (CAMMS223/CARE-MS I: 2.0; CARE-MS II: 2.7; OPERA I: 2.9; OPERA II: 2.8), mean MS duration (CAMMS223/CARE-MS I: 1.9 years; CARE-MS II: 4.5 years; OPERA I and II: 6.7 years in each study), and mean number of relapses in the previous 2 years (CAMMS223/CARE-MS I: 2.5; CARE-MS II: 2.8; OPERA I and II: 1.8 in each study) varied across studies. Both alemtuzumab and ocrelizumab significantly reduced ARR and CDW versus SC IFNB-1a. NNT values to prevent one relapse versus SC IFNB-1a were lower with alemtuzumab (CAMMS223/CARE-MS I: 5; CARE-MS II: 4) than ocrelizumab (OPERA I/II: 8 in each study), as were NNT values to prevent one patient from experiencing relapse (CAMMS223/CARE-MS I and CARE-MS II: 6 in each study; OPERA I and II: 8 in each study), and to prevent one patient from experiencing 6-month CDW (CAMMS223/CARE-MS I: 15; CARE-MS II: 13; OPERA I: 23; OPERA II: 21). 

Conclusions: Although populations in the available datasets differ, 2-year analyses show that fewer patients required treatment with alemtuzumab than ocrelizumab to prevent one relapse, to prevent relapse in one patient, and to prevent 6-month confirmed disability worsening in one patient versus SC IFNB-1a. Further clinical experience will help confirm these findings.