Clinical and cognitive outcomes in Ocrelizumab-treated MS patients: Insights into the wearing-off phenomenon

Ocrelizumab (OCR) has proven effective in altering the disease trajectory of multiple sclerosis (MS) patients. However, many patients experience a preinfusion "wearing-off phenomenon" (WoP) characterized by a resurgence of MS symptoms. This study aimed to investigate the relationships between WoP and various clinical, functional, and cognitive parameters and to compare demographic and radiological data between patients with and without WoP.

This prospective study was conducted across two MS centers and included 84 MS patients aged 18-70 years who had received at least two OCR doses. Clinical disability was assessed via the Expanded Disability Status Scale (EDSS), whereas cognitive function was evaluated via the Symbol Digit Modalities Test (SDMT). The functional outcomes were measured via the nine-hole peg test (9HPT) and the 25-Foot Walk Test (25FWT). Immunoglobulin G (IgG) levels were monitored, and radiological activity was tracked through MRI.

Among the 84 patients, 58.3% experienced WoP, predominantly starting more than four weeks before their scheduled infusion. Patients with WoP had significantly shorter disease durations, lower IgG levels, and more gadolinium-enhancing lesions than did those without WoP (p < 0.05). Preinfusion 25FWT times were significantly longer in the WoP group (p = 0.025), although cognitive and functional assessments postinfusion were not significantly different between the groups.

WoP is a prevalent phenomenon among OCR-treated MS patients, characterized by transient functional impairments, particularly in motor performance, that resolve postinfusion. Its association with shorter disease duration, lower IgG levels, and increased radiological activity underscores the need for personalized treatment approaches. While standardized dosing schedules are effective for many, optimizing infusion intervals based on patient-specific clinical and immunological factors may enhance outcomes and mitigate symptom recurrence in OCR therapy for MS.