Long‐Term Clinical and Psychological Efficacy and Safety of Ocrelizumab in People With Multiple Sclerosis: A Real‐World Longitudinal Study

ABSTRACT Background Multiple sclerosis (MS) is the most prevalent immune‐mediated neurodegenerative disease affecting the central nervous system. Ocrelizumab, a humanized anti‐CD20 monoclonal antibody, has demonstrated significant efficacy in reducing disease activity and improving clinical outcomes of people with MS (PwMS) in clinical trials. However, real‐world data are crucial for assessing the efficacy and safety of ocrelizumab. Thus, the current study aimed to evaluate the long‐term clinical and psychological efficacy and safety profile of ocrelizumab in PwMS compared with other disease‐modifying therapies (DMTs). Methods This longitudinal study was carried out between January 2022 and February 2024 in Isfahan, Iran. 51 PwMS were included, of whom 21 patients were DMT‐naïve, while 30 patients were on other DMTs, including interferon‐β, fingolimod, dimethyl fumarate, natalizumab, or teriflunomide. Demographic characteristics, clinical outcomes, including Expanded Disability Status Scale (EDSS), annualized relapse rate (ARR), timed 25‐foot walk (T25FW) test, and nine‐hole peg test (9‐HPT), as well as psychological measures including anxiety, depression, and fatigue, were evaluated at baseline (T0), and 12 months (T1) and 24 months (T2) of follow‐up. Adverse events (AEs) were obtained using chart review and patient self‐reports in clinical visits. Results ARR was significantly decreased at T1 (Z = −5.4, p < 0.001) and T2 (Z = −4.03, p < 0.001) in PwMS who received ocrelizumab. Similarly, a significant decrease was found in 9‐HPT (Z = −5.16, p < 0.001) and T25FW (Cohen's d = −0.72, p < 0.001) at T1. Depression and fatigue significantly improved at T1 (Z = −3.89, p < 0.001, Cohen's d = −1.16, p < 0.001, respectively) and further at T2 (Z = −2.18, p = 0.029, Cohen's d = −1.59, p < 0.001, respectively), and anxiety at T1 (Z = −3, p = 0.003). PwMS who initiated ocrelizumab as a first‐line therapy showed a significantly greater reduction in ARR, 9‐HPT, and T25FW than those previously treated with other DMTs (all p < 0.05), while no significant differences were observed in terms of changing EDSS, anxiety, depression, or fatigue levels. Respiratory infections (13.7%), infusion‐related reactions (5.9%), and headache (5.9%) were the most frequent AEs, and no serious infection was observed. Conclusion Ocrelizumab may reduce disease activity and improve functional and psychological outcomes in PwMS, while maintaining a favorable safety profile. Moreover, relapse rates and functional impairment were improved more in groups that initiated ocrelizumab as a first‐line therapy than in other disease‐modifying therapies. These findings suggest that ocrelizumab is a promising first‐line treatment in MS. However, further studies are needed to confirm these preliminary results.