Multiple sclerosis is a chronic autoimmune disease of the central nervous system, characterized by inflammatory demyelinating lesions and progressive neurodegeneration. With the introduction of highly effective drugs that modify the course of the disease, the prognosis of
patients with multiple sclerosis has significantly improved. Despite their high efficacy, these drugs are associated with an increased risk of serious side effects, especially infections, so their monitoring in a real-world setting is of key importance.
The purpose of the master's thesis was to analyze the side effects of selected highly effective drugs for the treatment of multiple sclerosis - ofatumumab (Kesimpta), alemtuzumab
(Lemtrada), cladribine (Mavenclad), ocrelizumab (Ocrevus) and natalizumab (Tysabri and Tyruko) based on reports from the European pharmacovigilance database EudraVigilance. The
analysis included the distribution of reports by gender, age and years, a detailed discussion of the group of infectious and parasitic diseases according to the MedDRA classification, and the frequency of reporting at different MedDRA levels. A disproportionality analysis was performed to assess the association between individual drugs and specific infections by calculating the reporting odds ratio (ROR).
In total, more than 15,000 reports and 38,000 adverse reactions were analyzed from the time the drug was launched on the market until March 22, 2025. For all active substances, the most frequently reported adverse reactions were from the groups of infectious and parasitic diseases,
nervous system disorders and investigations (i.e. elevated or decreased levels of liver enzymes, blood creatinine, abnormal electrocardiogram results, elevated body temperature, etc.). For ofatumumab, alemtuzumab, cladribine and ocrelizumab, the most frequently reported were
upper and lower respiratory tract infections, herpes virus infections and urinary tract infections. The most adverse effects were reported for natalizumab, which has also been on the market the
longest.
The disproportionality analysis, which was performed at three levels (PT, HLT, SMQ), confirmed already known and clinically established safety signals, such as progressive
multifocal leukoencephalopathy with natalizumab (ROR 55.29; 95% CI 35.82-85.37), listeriosis with alemtuzumab (ROR 36.24; 95% CI 4.46-294.69), and herpesvirus infections
(ROR 2.08; 95% CI 1.70-2.50), specifically herpes zoster (ROR 2.12; 95% CI 1.61-2.79) with cladribine. At the same time, enhanced signals were detected for some serious infections with ocrelizumab, namely infections of the central nervous system and spinal cord (ROR 2.27; 95% CI 1.41-3.64), specifically meningitis (ROR 2.64; 95% CI 1.04-6.71). Ofatumumab has been on the market for the shortest time, and consequently has the fewest signals. The findings of the master's thesis emphasize the importance of continuous pharmacovigilance monitoring of
modern therapies for multiple sclerosis and contribute to a better understanding of their safety profile in clinical practice.
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