Number-Needed-to-Treat Analyses Comparing Clinical Disease Outcomes and Disability Improvement in RMS Patients Treated with Alemtuzumab or Ocrelizumab

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
Aaron Boster, MD , OhioHealth Neurological Physicians, Columbus, OH
Bart Van Wijmeersch, MD, PhD , Rehabilitation & MS-Centre Overpelt, BIOMED, Hasselt University, Hasselt, Belgium
Raed Alroughani, MD , Amiri Hospital, Sharq, Kuwait
Giancarlo Comi, MD , University Vita-Salute San Raffaele, Milan, Italy
Regina Berkovich, MD, PhD , University of Southern California, Keck School of Medicine, Los Angeles, CA
Guillermo Izquierdo, MD , Virgen Macarena University Hospital, Seville, Spain
Daniel Kantor, MD , Florida Atlantic University, Boca Raton, FL
Christopher LaGanke, MD , North Central Neurology Associates, Cullman, AL
Volker Limmroth, MD, PhD , Klinik fur Neurologie und Palliativmedizin, Cologne, Germany
Richard AL Macdonell, MD , Austin Health and Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
Heinz Wiendl, MD , University of Munster, Munster, Germany
Maria Melanson, MD, PhD , Sanofi, Cambridge, MA
Karthinathan Thangavelu, PhD , Sanofi, Cambridge, MA
Mark S Freedman, MD , University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada
on behalf of the CAMMS223, CARE-MS I, and CARE-MS II, Investigators , on behalf of the CAMMS223, CARE-MS I, and CARE-MS II Investigators, NA, NJ

Background: In the absence of head-to-head trials, the number-needed-to-treat (NNT) may be used to assess comparative efficacy of disease-modifying therapies. Alemtuzumab and ocrelizumab significantly improved clinical efficacy outcomes in relapsing multiple sclerosis (RMS) patients vs SC IFNB-1a 44 µg 3x/week (common comparator) in 2-year (y) randomized clinical trials.

Objectives: Determine the NNT to prevent clinical disease events and improve disability in studies of RMS patients treated with alemtuzumab or ocrelizumab vs SC IFNB-1a.

Methods: NNT values were derived from post hoc analyses of 2-y study data of alemtuzumab (pooled treatment-naive patients [CAMMS223, NCT00050778; CARE-MS I, NCT00530348; N=786]; patients with inadequate response to prior therapy [CARE-MS II, NCT00548405; N=628]) and ocrelizumab (OPERA I [NCT01247324, N=821]; OPERA II [NCT01412333, N=835]). Alemtuzumab 12 mg/day IV was administered as 2 courses (baseline [BL]: 5 days; 12 months later: 3 days); ocrelizumab IV was administered at BL and Day 15 (300 mg/day each), then Weeks 24, 48, 72 (600 mg/day each). NNT was based on inverse of absolute risk differences vs SC IFNB-1a for annualized relapse rate, clinical disease activity (CDA; ≥1 relapse or 6-month confirmed disability worsening [CDW]), and 6-month confirmed disability improvement (CDI); the Altman method was used for CDW. Lower NNT values suggest greater efficacy.

Results: At BL, 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 y; CARE-MS II: 4.5 y; OPERA I/II: both 6.7 y), and mean number of relapses in the previous 2 y (CAMMS223/CARE-MS I: 2.5; CARE-MS II: 2.8; OPERA I/II: both 1.8) varied across trials. The NNT values vs SC IFNB-1a were lower with alemtuzumab than ocrelizumab to prevent: 1 relapse (CAMMS223/CARE-MS I: 5; CARE-MS II: 4; OPERA I/II: 8 each), CDW in 1 patient (CAMMS223/CARE-MS I: 15; CARE-MS II: 13; OPERA I: 23; OPERA II: 21), and CDA in 1 patient (CAMMS223/CARE-MS I: 5; CARE-MS II: 6; OPERA I/II: 8 each). The NNT value vs SC IFNB-1a to achieve CDI in 1 patient was also lower with alemtuzumab than ocrelizumab (pooled CAMMS223/CARE-MS I/CARE-MS II: 10; pooled OPERA I/II: 25).

Conclusions: Despite population differences, NNT values to prevent clinical events and achieve CDI over 2 y were lower with alemtuzumab than ocrelizumab in SC IFNB-1a comparator studies. Further real-world clinical experience will help confirm these findings.

 Study Support: Sanofi and Bayer HealthCare Pharmaceuticals.