Association of body mass index and clinical response in patients receiving ofatumumab for treatment of multiple sclerosis

J Neurol Neurosurg Psychiatry. 2025 Mar 6:jnnp-2024-335673. doi: 10.1136/jnnp-2024-335673. Online ahead of print.

Abstract

Background: The impact of body weight on disability progression rates among patients receiving ofatumumab was not evaluated yet.

Methods: Among patients from a multicentre prospective cohort, baseline demographics were compared among body mass index (BMI) quartiles as well as proportions of clinical relapses, MRI lesions and disability worsening during follow-up.

Results: 536 patients from four centres were included. Baseline demographics were evenly distributed among patients. Proportions of relapses and new/enlarging MRI lesions were comparable among BMI strata.Confirmed disability worsening was significantly more abundant among patients from the 4th BMI quartile (BMI ≥29.2 kg/m2; adjusted HR: 3.33 (95% CI: 1.72 to 6.42; p<0.001). Relapse-associated worsening was not substantially different among relapsing patients from different BMI strata (HR: 1.19 (95% CI: 0.40 to 3.52; p=0.750)). Yet, progression independent from relapse activity was more likely in patients from 4th BMI quartile (HR: 2.00 (95% CI: 1.47 to 2.70; p<0.001)).Body weight (4th body weight quartile: ≥84.5 kg) was not associated with disability worsening (adjusted HR: 1.91 (95% CI: 0.97 to 3.76; p=0.060). Ofatumumab serum levels were lower in patients with higher BMI as well.

Conclusions: Inflammatory disease outcomes did not differ but disability progression was more frequent in the highest BMI quartile (BMI >29.2 kg/m2). This was associated with lower ofatumumab serum levels. Since body weight itself was not predictive, we assume that body fat composition is critical for ofatumumab effectiveness.

Keywords: MULTIPLE SCLEROSIS; NEUROIMMUNOLOGY.