B-Cell Depletion and Efficacy Outcomes of Ofatumumab Are Consistent Across Different Body Mass Index Categories: Insights from ASCLEPIOS I and II Trials
Anne Cross1, Stephen Hauser2, Heinz Wiendl3, Amit Bar-Or4, Patricia Coyle5, Xavier Montalban6, Jerome De Seze7, Haoyi Fu8, Alit Bhatt9, Ibolya Boer10, Ludwig Kappos11
1Washington University School of Medicine, Saint Louis, MO, USA, 2UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA, 3University of Münster, Münster, Germany, 4Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, USA, 5Department of Neurology, Stony Brook University, Stony Brook, NY, USA, 6Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitario Vall d'Hebron, Barcelona, Spain, 7University Hospital of Strasbourg, Strasbourg, France, 8Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 9Novartis Healthcare Pvt. Ltd., Hyderabad, India, 10Novartis Pharma AG, Basel, Switzerland, 11Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) and MS Center, Departments of Headorgans, Spine and Neuromedicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland
Objective:

To evaluate the effect of ofatumumab on B-cell depletion and efficacy outcomes in the subgroup of patients from ASCLEPIOS I/II trials defined by their baseline body mass index (BMI).

Background:

In ASCLEPIOS I/II trials, ofatumumab demonstrated superior efficacy and favorable safety profile over teriflunomide in people with relapsing multiple sclerosis (pwRMS), with consistent results across different subgroups. BMI can be a possible confounding factor affecting MS disease activity.

Design/Methods:

Patients received either ofatumumab 20 mg or teriflunomide 14 mg for up to 30 months. Median B-cell counts and proportion of patients with low B-cell counts (≤10 cells/μL) over 96 weeks were assessed among patients categorized by typical BMI cutoffs (kg/m2) (<18.5 [n=76]; ≥18.5–<25.0 [n=921]; ≥25–<30 [n=511]; and ≥30.0 [n=372]) and baseline BMI quartiles (kg/m2) (Q1: <21.5; Q2: ≥21.5–<24.6; Q3: ≥24.6–<28.7; Q4: ≥28.7 [n=470 each]). Impact of different BMI categories on annualized relapse rate (ARR), time to 3/6-month confirmed disability worsening (3/6mCDW), number of gadolinium-enhancing (Gd+) T1 lesions, and annualized rate of new/enlarging T2 lesions (neT2) were assessed.

Results:

Across all BMI categories, median B-cell counts reduced rapidly with ofatumumab by Week (W)2 (≤10 cells/μL) and sustained at 0 cells/μL up to W96, whereas with teriflunomide, B-cell counts ranged between 115 and 190 cells/μL throughout the observation period. About >75% of ofatumumab-treated patients achieved B-cell counts ≤10 cells/μL at W2; ≥90% at W4 and maintained over the 96 weeks regardless of BMI. Reductions in ARR, 3m/6mCDW, Gd+ T1, and neT2 lesions favored ofatumumab versus teriflunomide across all BMI categories.

Conclusions:

Monthly 20 mg subcutaneous (SC) administration of ofatumumab showed a high degree of efficacy across pwRMS, independent of BMI, allowing for ease of use with no need of dose-adjustment. The approved dose and more frequent SC administration of ofatumumab seems to cover the full spectrum of BMI in pwRMS.

10.1212/WNL.0000000000206085