Before a medicine is approved for use, evidence of its safety and efficacy is limited to clinical trials. After marketing authorisation, the medicine can be used in larger numbers of patients, for longer periods of time and in combination with other medicines. In such circumstances, previously undetected adverse events may occur. Anaplastic lymphoma kinase inhibitors are an important class of drugs in the treatment of lung cancer, and the first drug in this class, crizotinib, was approved in 2012. In this Master's thesis, we aimed to investigate the safety profile of anaplastic lymphoma kinase inhibitors through an analysis of the adverse events reported in EudraVigilance in the post-authorisation period.
We undertook the analysis of adverse events by retrieving the reports of adverse events for all medicines from the EudraVigilance database, entering them into Excel, using SPSS to evaluate the statistical data and categorising each adverse event using the MedDRA medical dictionary.
During the 2012-2022 observation period, 4508 reports of suspected adverse events to all anaplastic lymphoma kinase inhibitors were reported to EudraVigilance, with crizotinib being the most frequently reported (43.4%), followed by alectinib (28.0%), lorlatinib (13.6%), ceritinib (9.0%) and lastly brigatinib (6.0%). The most common adverse event reported in EudraVigilance for each drug include oedema for crizotinib, diarrhoea and nausea for certinib, fatigue for alectinib, elevated blood creatine kinase levels for brigatinib and hypercholesterolaemia for lorlatinib. When comparing EudraVigilance with the Summary of Product Characteristics, we observed similarities in the frequency of some adverse events, such as oedema and hypercholesterolaemia, which occurred with high frequency in both databases, while some adverse event such as fatigue are less represented in EudraVigilance, probably due to their lower severity. Conversely, serious adverse events such as pneumonitis/interstitial lung disease, bradycardia and liver disease are more frequently reported in EudraVigilance. Comparison of selected adverse events revealed significant differences between individual anaplastic lymphoma kinase inhibitors, which may provide important guidance for use in clinical practice. The results of the thesis confirm the importance of post-authorisation monitoring and reporting of adverse events and of updating the safety information in the Summary of Product Characteristics.
|
