Wearing Off Rates Higher in Ocrelizumab Than Ofatumumab, Study Suggests

Brandon Brown

Findings from a non-interventional primary data collection study of adults with multiple sclerosis (MS) showed that significantly higher patients on ocrelizumab (Ocrevus; Genentech) experienced wearing off related symptom worsening while on medication than those prescribed ofatumumab (Kesimpta; Novartis).¹

The real-world study comprised 75 patients treated with ofatumumab for at least 6 months and 60 on ocrelizumab for at least 1 year. Between the 2 groups, median duration of MS and of treatment was shorter for ofatumumab (10 vs 14 years; 2 vs 5 years, respectively), and fewer ofatumumab-treated patients were taking other medications to manage MS symptoms (68% vs 83%).

In the trial, the proportions of patient experiencing worsening of MS symptoms from the beginning to the end of the treatment cycle were evaluated using 4 domains of the Neuro-QoL scale: fatigue, mobility, cognition, and depression. Presented at the 2025 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 28-31, in Phoenix, Arizona, fewer ofatumumab-treated patients self-reported an increase in MS symptoms (27% vs 50%; P <.05) from the start to the end of the index treatment cycle. In addition, this group was less likely to experience an increase in symptoms between doses, regardless of whether they had (28 of 75; 21%) or had not (47 of 75; 30%) previously received treatment with ocrelizumab.

Presented by Brandon Brown, medical director at Novartis, patients treated with ofatumumab were less likely to experience an increase in symptoms between doses compared with ocrelizumab, regardless of treatment duration. For ofatumumab, occurrence decreased with longer treatment duration (from <2 years to 2-4 years), whereas for ocrelizumab it increased, with rates after 4 years remaining similar to those in the first 2 years.

Statistical analyses focused on assessing symptom changes and quality of life over the treatment cycle. Researchers calculated the overall proportion of patients reporting increased symptoms on the global wearing-off question, with results further stratified by key patient and treatment subgroups. For each Neuro-QoL scale, they identified the proportion of patients whose scores worsened by more than 0.5 times the baseline standard deviation. Additionally, changes in the proportion of patients selecting one of the three most severe response categories on each scale item were evaluated from the beginning to the end of the treatment cycle.

Coming into the study, fewer patients on ofatumumab reported “usually” or “always” experiencing an increase in MS symptoms during previous treatment cycles (n = 8 [11%]; vs n = 13 [22%]; P = .13). At enrollment, among these patients who reported an increase, those on ofatumumab were less likely to experience an increase in symptoms for at least 1 week before the next scheduled dose (25% vs 100%, respectively).

During the index treatment cycle, those treated with ofatumumab showed significantly less deterioration on the Neuro-QoL Fatigue, Mobility, and Cognition scales compared with those prescribed ocrelizumab (all P <.05). Ocrelizumab-treated patients experienced notably larger increases in the frequency of symptoms related to these domains, while ofatumumab-treated patients had relatively smaller changes, indicating more stable symptom control and reduced wearing-off effects with ofatumumab. For the Depression scale, symptom frequency increases were slightly lower or comparable in the ofatumumab group compared with the ocrelizumab cohort.

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On the Neuro-QoL, patient-reported worsening on Fatigue was reported by 42% of those on ocrelizumab vs 23% of those on ofatumumab (P <.05). Similarly, 23% of ocrelizumab-treated patients reported worsening in mobility vs 4% of ofatumumab-treated individuals (P <.01). Patient-reported worsening in cognition was found in 30% of those on ocrelizumab vs 9% of those assigned to ofatumumab (P <.01).

Study authors concluded that the longer dosing interval associated with ocrelizumab may have contributed to the higher reported incidence of wearing-off symptoms, characterized by increased symptoms prior to next scheduled dose, although true disease activity could not be ruled out.

Wearing off effect has been previously documented for both treatments in various research settings. A small-scale study presented at the 2024 ECTRIMS Congress showed that nearly one-third of the 103-patient cohort of those with MS experienced end-of-dose phenomena (EOD) with ofatumumab. Dubbed ABANDONED-MS, the study revealed complaints regarding fatigue (27%), cognitive impairment (19%), and gait difficulties (16%). In addition, patients with EOD displayed worse performance in some subcategories of neuropsychiatric testing and reported decreased quality of life.²

For ocrelizumab, a study presented at the 2024 CMSC Annual Meeting, revealed that nearly 25% of patients with MS treated with the therapy experienced a wearing-off phenomenon. In this retrospective study of 528 patients, wearing-off commonly developed 2 to 4 weeks before the next infusion (59.5%), and more than 80% of those who developed wearing-off did so within the first 3 years of treatment. Risk factors included comorbid fatigue (OR, 2.10; P = .001), and non-White race (OR, 2.19; P = .018), while protective factors included male sex (OR, 0.56; P = .026) and Hispanic ethnicity (OR, 0.48; P = .029).³

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REFERENCES
1. Brown B, Thakkar K, Schmidt H, et al. LBA16 - The Wearing-Off Effect of Two Anti-CD20 Therapies in Patients with Multiple Sclerosis: Ofatumumab and Ocrelizumab. Presented at: 2025 CMSC Annual Meeting; May 28-31; Phoenix, Arizona. Abstract LBA16.
2. Winter P, Wolff S, Doerr J, et al. Abundance and impact of end-of-dose symptoms among patients receiving Ofatumumab for treatment of active disease in multiple sclerosis (ABANDONED-MS). Presented at: ECTRIMS Congress; September 18-20, 2024; ABSTRACT P1586/196
3. 25% of Patients With MS Treated with Ocrevus Report Wearing-Off Phenomenon. Presented at: 2024 CMSC Annual Meeting. https://practicalneurology.com/news/25-of-patients-with-ms-treated-with-ocrevus-report-wearing-off-phenomenon/2470480/