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).

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.

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.

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.

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.