Pharmacovigilance and Multiple Sclerosis (MS): drugs as risk factors for MS, and safety profile of drugs used in MS treatment

Several risk factors have been associated with Multiple Sclerosis onset (MSo). However, the role of previous drug exposure in MSo is far to be completely elucidated. In this intricate scenario, another important issue is represented by the safety profile of MS therapies. This thesis aimed to explore the role of drugs as possible risk factor in MSo by performing an evidence mapping of literature and a disproportionality analysis by using the FDA-Adverse Event Reporting System (FAERS) database. In the last part of the thesis, signal of Drug Induced Liver Injury (DILI) events during MS therapies was assessed by using in the same database. The analysis of the literature showed that drugs acting on immune system, hormone balance and infections were suspected as possible cause of MSo in case reports and case series, whereas contrasting results emerged from the few longitudinal studies. These data were in part in line with FAERS analysis, which resulted in disproportionality for drugs acting on immune system, insulin, bisphosphonates and contraceptives. Analysis of DILI events in MS treated patients suggests that a careful clinical monitoring should be applied to these patients. In addition, longitudinal studies should be planned in order to evaluate safety profile of MS drugs in monotherapy as well as in combination with other drugs. In conclusion, the submission of exhaustive reports of adverse drug reactions would permit stratified analyses and a better characterization of rare and unpredictable adverse events. Moreover, case-control studies performed on electronic medical records could confirm or refuse safety signals emerged from this thesis.