Postmarketing safety of migraine prophylactic monoclonal antibodies: An EudraVigilance database analysis of eptinezumab, fremanezumab, galcanezumab, and erenumab.

Abstract

Objectives/background: This study was undertaken to evaluate the postmarketing safety of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide pathway used for migraine prophylaxis through pharmacovigilance data analysis by examining suspected adverse events reported in Europe. Migraine is one of the most prevalent and debilitating neurological disorders globally. The introduction of mAbs targeting the calcitonin gene-related peptide pathway has transformed migraine prophylaxis. However, their safety profiles in real-world settings are not fully established, and ongoing safety monitoring is essential, as clinical trials may not capture all potential adverse drug reactions associated with new therapies.

Methods: A disproportionality analysis was carried out by analyzing postmarketing pharmacovigilance data from the EudraVigilance database, focusing on four mAbs: eptinezumab, fremanezumab, galcanezumab, and erenumab. Descriptive and statistical analyses were performed on data retrieved from the date of marketing authorization of each medicine up to June 16, 2024. The reporting odds ratio (ROR), information component, and empirical Bayes geometric mean were calculated to detect signals of disproportionate reporting comparing their safety profiles to topiramate, a standard preventive migraine treatment.

Results: A total of 14,285 reports had emerged; most of them were from females and concerned patients aged 18-64 years. The most frequently reported adverse drug reactions were primarily nonserious, aligning with literature and previously established safety profiles, such as fatigue and injection site reactions. The statistical analysis revealed 15 significant disproportionality signals: 11 for eptinezumab and four for galcanezumab. Eptinezumab highlighted potential new safety signals such as palpitations (ROR = 6.93, 95% confidence interval [CI] = 3.39-14.18), oropharyngeal pain (ROR = 7.19, 95% CI = 3.40-15.24), and erythema (ROR = 12.31, 95% CI = 4.58-33.12). These findings suggest a potential class effect, warranting further investigations and highlighting the importance of continued monitoring regarding the long-term safety of mAbs.

Conclusion: Almost all of the most reported and statistically significant adverse events were nonserious and consistent with the existing literature. Given the chronic nature of migraine treatment, continuous pharmacovigilance monitoring is essential to ensure their constant safe use in clinical practice.