End-of-Dose Phenomena Observed in Multiple Sclerosis Patients on Ofatumumab
核心洞察
A study of 103 MS patients found that 34% experienced end-of-dose phenomena (EOD) with ofatumumab, impacting their quality of life.
EOD was associated with higher baseline disability, longer disease duration, and older age, highlighting the need for careful monitoring.
Fatigue, cognitive impairment, and gait difficulties were the most commonly reported EOD symptoms among patients on ofatumumab.
A recent study presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (搜索) (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 (搜索) 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 (搜索) 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 (搜索) 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).