Association Between Disease-Modifying Therapies Prescribed to Persons with Multiple Sclerosis and Cancer: a WHO Pharmacovigilance Database Analysis

Abstract

The risk of cancer associated with persons with multiple sclerosis (pwMS) prescribed with disease modifying therapies (DMTs) is not well established. This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database: VigiBase®. All consecutive reports of DMTs prescribed to pwMS (alemtuzumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon-β, natalizumab, ocrelizumab, and teriflunomide), and their serious adverse event cases were eligible, excluding those reporting immunosuppressant DMTs used as anticancer therapies. The primary outcome was the multivariate odds ratio of cancer reporting (r-OR) for DMTs prescribed to pwMS after imputation of missing data. There were 5966 cancer cases from 240,993 reports of DMTs prescribed to pwMS. After adjustments on age, sex, and geographical region, natalizumab (r-OR 1.74, 95% CI 1.63-1.87), interferon-β (r-OR 1.39, 95% CI 1.30-1.49), dimethyl fumarate (r-OR 1.35, 95% CI 1.25-1.46), and fingolimod (r-OR 1.15, 95% CI 1.06-1.24) were significantly associated with a greater cancer reporting, whereas alemtuzumab, glatiramer acetate, ocrelizumab, and teriflunomide were not, in the disproportionality analysis. As exploratory analyses, upper aerodigestive tract, breast, urinary including the male genitourinary tract, and nervous system cancers were associated with natalizumab, interferon-β, and dimethyl fumarate. Fingolimod was only associated with skin cancer types. Cancer cases reporting these four DMTs prescribed to pwMS were younger in age than for non-pwMS drugs in the VigiBase® (p < 0.0001). A close and regular cancer screening in pwMS treated with natalizumab, interferon-β, dimethyl fumarate, and fingolimod may be warranted, even for persons at a younger age. Trial Registration NCT04237337.

Fig. 1

Flowchart of the reports selection (DMT, disease-modifying therapy; MS, multiple sclerosis. DMTs prescribed to persons with MS (pwMS) were alemtuzumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon-β, natalizumab, ocrelizumab, and teriflunomide)

Fig. 2

Disproportionality analysis for the association of disease-modifying therapies (DMTs) prescribed to persons with multiple sclerosis (pwMS) and cancer reporting (CI, confidence interval; r-OR, reporting odds ratio. Adjustment variables: age, sex, and geographical region)