Category: Fellows Posters
Multiple sclerosis (MS) is an inflammatory, neurodegenerative, and demyelinating disease affecting nearly 1 million adults in the US with estimated annual costs of $28 billion. MS is ranked among the top chronic conditions by pharmaceutical expenditures in many health systems. An increasing number of biologic disease-modifying therapies have been approved to reduce MS relapses but long-term data on treatment complications are limited, creating challenges in assessing safety and cost-effectiveness of these therapies. This study evaluated reports of safety and efficacy submitted to the FDA Adverse Event Reporting System (FAERS) between 1993 and 2019 for therapeutic biologics used in MS.
A retrospective analysis was conducted on data publicly available through FAERS. Cases involving a single biologic with reported use for MS were selected for inclusion in the study. Daclizumab reports were included in this study although the product was withdrawn from the market in 2018 due to safety concerns. Reporting odds ratios (RORs) and 95% confidence intervals (CI) were used to identify signals of disproportionate reporting in adverse reactions and drug ineffectiveness among biologics used in MS, including brand formulations. Due to inclusion of off-label use (i.e. rituximab), sub-analysis was performed to compare reports of safety and efficacy for rituximab use in MS and FDA-labeled indications.
A total of 275,992 reported cases were identified in the FAERS database in which interferon beta-1a, interferon beta-1b, peginterferon beta-1a, natalizumab, ocrelizumab, alemtuzumab, daclizumab, or rituximab were used for MS. Serious outcomes, including death, were reported in 113,574 cases (41.15%) and drug ineffectiveness in 7,393 cases (2.68%). Disproportionality reporting signals were detected for serious adverse events among patients using peginterferon beta-1a (ROR [95%CI]=2.32 [2.06, 2.61]) and for drug ineffectiveness among patients using natalizumab (ROR=1.71 [1.53, 1.92]). Disproportionality signals for serious adverse events across brand formulations of the same active biologic in patients using interferon beta-1b (ROR=40.50 [29.45, 55.71]) and interferon beta-1a (ROR=4.39 [4.22, 4.57]) were identified. Compared to the reference natalizumab, disproportionality signals for serious adverse event reporting were detected for all other monoclonal antibodies: ocrelizumab (ROR=3.13 [2.95, 3.31]), alemtuzumab (ROR=20.11 [17.95, 22.52]), daclizumab (ROR=2.85 [2.54, 3.11]), and rituximab (ROR=5.21 [4.33, 6.26]). Rituximab had 4,413 of 17,553 cases (30.3%) reported for off-label indications, of which 474 cases (3.3%) were used in MS. Signals for serious adverse event reporting were lower for off-label rituximab use in MS (ROR=0.32 [0.26, 0.39]) in comparison with rituximab use in FDA-labeled indications.
This study identified disproportionate reporting signals of safety and efficacy associated with biologics used in multiple sclerosis. Evaluation of long-term clinical effects and risks, including immunological complications, is needed due to the growing interest in early initiation of monoclonal antibodies for multiple sclerosis patients. Although causality cannot be determined through use of signals identified from voluntary reporting systems, analysis of FAERS is a valuable part of the ongoing surveillance of the safety and efficacy of biologics in clinical practice.