Safety of Monoclonal Antibodies in the Treatment of Multiple Sclerosis: A Post-marketing Active Surveillance Study in Saudi Arabia

Abstract Introduction: The prevalence of multiple sclerosis (MS) has significantly increased worldwide and in Saudi Arabia over time. Although there is still no cure available for MS, monoclonal antibodies (MABs) are one of the preferred treatments due to their efficacy; however, their safety profile remains uncertain. Materials and Methods: This retrospective cohort study included patients who were treated with one of the MABs (natalizumab, ocrelizumab, rituximab, or alemtuzumab) for MS or who had had treatment discontinued for any reason between January 2015 and December 2021. The study was conducted using electronic health records from King Abdulaziz Medical City-Central Region (CR), a tertiary hospital in Riyadh, Saudi Arabia. The primary outcomes were to describe the reported adverse drug events (ADEs) and their incidences. The Medical Dictionary for Drug Regulatory Affairs was used to classify the ADEs according to the system organ classification and the preferred term. ADEs were classified based on seriousness and expectedness according to Saudi Food & Drug Authority guidelines on good pharmacovigilance practices. The secondary outcome was to describe the discontinuation reasons for MABs. Descriptive analyses were performed, including frequency/percentages for categorical variables and mean with standard deviation or median with range for continuous variables. Results: A total of 213 patient records were retrieved and reviewed for eligibility. Among the eligible cohort, 209 patients were on MAB infusion treatment, and 36 had their MAB infusion discontinued. Patients who were on MABs were using ocrelizumab (150), natalizumab (35), rituximab (20), or alemtuzumab (4). Females represented 66.2% of the study population, and the cohort’s average age was 33.33 years (±8.77). The most common ADEs were skin and subcutaneous tissue disorders (notably hair loss and rash), followed by psychiatric disorders such as depression. Serious adverse events (SAEs) were reported in 16 patients, mainly urinary, psychiatric, blood, neoplastic, and infectious disorders. For natalizumab, nervous system disorders (neurogenic bladder, ataxia, and sleep disorder) were the most frequent ADEs, with 19 SAEs including suicide attempt, depression, and cardiac and hepatic events. Rituximab and alemtuzumab were less commonly used; rituximab was associated primarily with skin disorders and migraines, while alemtuzumab caused mainly hematological, nervous, and renal SAEs. Discontinuation rate was observed most frequently among natalizumab users (47%), mainly for perceived risk of progressive multifocal leukoencephalopathy (PML) due to John Cunningham virus (JCV) positivity, and among rituximab users (20%), it was mainly due to lack of effect. Conclusion: These findings show an acceptable safety profile of infusion MABs among MS patients in Saudi Arabia. However, the outcomes should be interpreted cautiously due to the limited number of patients included in our study. Further epidemiological studies are needed to assess the short- and long-term safety outcomes of these medications.