A recent study presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) revealed that over a third of multiple sclerosis (MS) patients treated with ofatumumab (Kesimpta; Novartis) experienced end-of-dose (EOD) phenomena. The findings underscore the importance of monitoring patients on ofatumumab for EOD, especially those with higher baseline disability, longer disease duration, and older age.
ABANDONED-MS Study Details
The ABANDONED-MS study, led by Steffen Pfeuffer, MD, from the University of Giessen, screened 103 patients to assess the prevalence of EOD. Patients were evaluated during week 4 of a treatment course (“off phase”) and week 1 of a subsequent course (“on-phase”). Assessments included neuropsychiatric outcomes, Multiple Sclerosis Functional Composite (MSFC) scores, and Expanded Disability Status Scale (EDSS) scores.
Key Findings on End-of-Dose Phenomena
The study found that 35 of the 103 patients (34%) experienced EOD with ofatumumab. The most common symptoms reported were fatigue (27%), cognitive impairment (19%), and gait difficulties (16%). Patients with EOD also showed worse performance in neuropsychiatric testing subcategories and reported a decreased quality of life. Notably, there were no significant differences in CD19+ B cell depletion between EOD and non-EOD patients.
Ofatumumab and Wearing-Off Effect
Ofatumumab, a fully-humanized monoclonal anti-CD20 antibody, has been approved for relapsing forms of MS since 2021. It selectively targets CD20-expressing B-cells, leading to their depletion through various mechanisms. A separate 2024 study published in the Multiple Sclerosis Journal: Experimental, Translational, and Clinical assessed the wearing-off effect in MS medications. This study indicated that patients on ofatumumab, administered as a once-monthly subcutaneous injection, had an 18.2% lower odds of experiencing the wearing-off effect compared to those treated with ocrelizumab (Ocrevus; Roche).
The wearing-off effect was reported in 54.7% of 258 patients from a tertiary MS center taking natalizumab, ocrelizumab, ofatumumab, or rituximab. After adjusting for confounders, ofatumumab was the only treatment associated with lower odds of the wearing-off phenomenon relative to ocrelizumab. This suggests potential differences in B-cell depletion effects between the two drugs or a placebo effect from the more frequent dosing of ofatumumab.
Real-World Efficacy and Persistence
Real-world data presented at the 2024 American Academy of Neurology Annual Meeting highlighted the persistence of ofatumumab compared to self-injectable or oral disease-modifying therapies (DMTs). At 6 months, persistence rates for ofatumumab vs self-injectable DMTs were 80.8% vs 56.7% (P < 0.001), and at 12 months, 74.5% vs 43.2% (P < 0.001). When compared to oral DMTs, persistence rates at 6 months were 81.9% vs 77.8% (P = 0.002), and at 12 months, 76.3% vs 64.6% (P = 0.002).
