Retinoids are not linked to risk of multiple sclerosis: A Danish nationwide cohort study.

Filipe Cortes-Figueiredo, Nete Munk Nielsen, Egon Stenager, Friedemann Paul, Jesper Hallas, Kasper Bruun Kristensen

Journal: European journal of neurology 2022;29(1):247-256

PMID: 34536255

Abstract

BACKGROUND AND PURPOSE

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system with an undetermined etiology. Retinoids may have immunomodulatory effects that favorably influence MS progression. We aimed to explore the yet unknown relationship between exposure to retinoids and the risk of acquiring MS.

METHODS

We performed a nationwide cohort study in the Danish population in the period 1998-2016, comparing MS incidence in three groups: users of systemic retinoids; users of topical retinoids (negative control group); and users of non-retinoid acne drugs (control group). We used data from the Danish Multiple Sclerosis Registry (DMSR), the Danish National Prescription Registry and the Danish National Patient Registry. Linkage was obtained through the personal identification number (CPR number). We addressed confounding by three-way propensity score (PS)-matching weights. Additionally, to evaluate a cumulative dose-response effect for systemic retinoids on MS incidence, we conducted a case-control study, nested within the cohort.

RESULTS

A total of 257,193 users of non-retinoid acne drugs, 130,560 users of topical retinoids, and 75,610 users of systemic retinoids were included. Systemic retinoid use was not associated with a reduced risk of MS compared to non-retinoid acne drug use in crude (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.61 to 1.05]) and weighted analyses (HR 0.89, 95% CI 0.67 to 1.20). There was no evidence of a cumulative dose-response association between systemic retinoids and MS incidence.

CONCLUSIONS

Use of systemic retinoids was not associated with a reduced incidence of MS compared to use of non-retinoid acne drugs in this study.

© 2021 European Academy of Neurology.

Address: VMorais Lab - Mitochondria Biology and Neurodegeneration, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.; Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.; Focused Research Unit in Neurology, Department of Neurology, Hospital of Southern Jutland, University of Southern Denmark, Denmark.; MS-clinic of Southern Jutland (Sønderborg, Esbjerg, Kolding), Department of Neurology, Hospital of Southern Jutland, Sønderborg, Denmark.; Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.; Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
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