Objective:

This observational, cross-sectional pharmacovigilance study aimed to investigate the association between disease-modifying therapies (DMT) for multiple sclerosis (MS) and cancer reporting using adverse event reports from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. 

Background:

Current evidence regarding the potential malignancy risk of MS DMTs remains conflicting.

Design/Methods:

We performed disproportionality analyses using FAERS data from 2004 to 2024. Adverse events were identified using the Medical Dictionary for Regulatory Activities standardized queries of “malignant and unspecified tumours” and  its subcategories, as well as malignancy-related subcategories under the system organ class “neoplasms benign, malignant and unspecified”. For DMTs approved by the FDA solely for the indication of MS, all reports were included; for DMTs with additional indications, only reports specifying “MS” as the indication were analyzed. Reporting odds ratio (ROR) and proportional reporting ratio were calculated to detect safety signals between DMTs and cancer reporting.

Results:

No association was found between any DMT and overall malignancy, non-hematologic malignancy, or hematologic malignancy reporting. Subgroup analyses identified positive safety signals for specific malignancy subgroups with ROR (95% confidence intervals) values as follows: for alemtuzumab, non-Hodgkin B-cell lymphoma 6.49 (2.67–15.81), endocrine neoplasms malignant and unspecified (NMU) 3.63 (2.09–6.28), and skin NMU 2.99 (2.00–4.49); for fingolimod, skin NMU 4.33 (4.02–4.66) and non-Hodgkin T-cell lymphoma 2.15 (1.57–2.97); for cladribine, leukemias 2.43 (1.43–4.13) and renal and urinary tract NMU 2.18 (1.23–3.86); for rituximab, gastrointestinal NMU 3.13 (1.93–5.06); for other S1P modulators, skin NMU 2.04 (1.54–2.68); for interferon beta-1a, nervous system NMU 2.82 (2.56–3.10) and endocrine NMU 2.45 (2.23–2.69); and for interferon beta-1b, endocrine NMU 2.30 (1.78–2.98).

Conclusions:

No association was found between DMTs and overall cancer reporting. However, several subgroup analyses demonstrated positive safety signals, underscoring the need for population-based studies to provide more definitive evidence.