Subgroup Analysis Reveals Ofatumumab’s Potent Efficacy in Highly Active Relapsing MS

Recent data from a post hoc subgroup analysis of the phase 3 ASCLEPIOS I/II trials provides compelling evidence for the use of ofatumumab (Kesimpta; Novartis) in patients with highly active relapsing multiple sclerosis (MS). Ofatumumab, a fully human anti-CD20 monoclonal antibody administered via a 20 mg subcutaneous monthly regimen, is currently the only self-administered anti-CD20 therapy approved for relapsing MS.¹

This latest analysis, presented at the Consortium of Multiple Sclerosis Centers (CMSC) 40th Annual Meeting, highlights the drug’s ability to suppress inflammatory activity and reduce the risk of disability progression in patients with the most aggressive disease phenotypes.

Addressing the High-Activity Challenge

Although ofatumumab had already demonstrated superiority over teriflunomide (Aubagio; Sanofi) in the broader relapsing MS population, data regarding its specific impact on patients with highly active disease remained limited. To bridge this gap, researchers analyzed a subgroup of 212 participants from the ASCLEPIOS I/II trials who met stringent criteria for high disease activity: having at least 1 gadolinium-enhancing (Gd+) lesion at baseline and 2 or more relapses in the year prior to screening.¹

Baseline characteristics between the treatment arms—101 patients receiving ofatumumab and 111 receiving teriflunomide—were well balanced. On average, these patients were approximately 35 years old and had been living with an MS diagnosis for roughly 4 years.

Unprecedented Suppression of Inflammatory Activity

The efficacy results in this high-risk subgroup were striking. Ofatumumab achieved a 49.6% reduction in the annualized relapse rate (ARR) compared to teriflunomide (p = 0.003). Even more profound was the impact on magnetic resonance imaging (MRI) markers of disease activity. Ofatumumab was associated with a 97.3% reduction in the mean number of Gd+ T1 lesions and an 81.5% reduction in new or enlarging T2 lesions (p < 0.001 for both).¹

For pharmacists monitoring long-term outcomes, the No Evidence of Disease Activity (NEDA-3) metrics are particularly noteworthy. By the second year of treatment, the odds of achieving NEDA-3 were nearly 20-fold higher for patients on ofatumumab compared to those on teriflunomide (overall response: 18.94; p < 0.001).

Neuroprotection and Disability Management

The analysis also extended to biomarkers and physical progression. Serum neurofilament light chain levels—a key indicator of neuroaxonal damage—were significantly lower in the ofatumumab group, showing reductions of 39.3% at month 12 and 41.8% at month 24 compared to teriflunomide (p < 0.001).¹

Furthermore, ofatumumab showed a numerical trend toward reducing disability progression. There was a 50.9% reduction in the risk of 3-month confirmed disability worsening and a 50.3% reduction in 6-month confirmed disability worsening.¹

Safety and Monitoring Considerations

From a safety perspective, ofatumumab’s profile in the highly active subgroup was consistent with the overall ASCLEPIOS population. The most common adverse events were injection-related reactions (21.8%) and nasopharyngitis (17.8%). Importantly, there were no deaths or unexpected safety signals reported.¹

Pharmacists should note that although mean IgM levels initially decreased before stabilizing, both IgG and IgM levels remained above the lower limit of normal in the vast majority of participants (98% and 80%, respectively) throughout the assessment period.¹

Clinical Implications

These findings reinforce the role of ofatumumab as a high-efficacy first-line or switch option for relapsing MS. By providing a potent, self-administered B-cell therapy, ofatumumab offers a balance of clinical robust efficacy and patient convenience, even for those facing the most active forms of the disease. These data support the initiation of ofatumumab across all levels of MS disease activity.¹

REFERENCE

Coyle P. Efficacy and safety of ofatumumab versus teriflunomide in participants with highly active relapsing mS: subgroup analysis from ASCLEPIOS I/II. Presented at: Consortium of Multiple Sclerosis Centers (CMSC) 40th Annual Meeting. May 29, 2026. Charlotte, NC.