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

*Kontaktforfatter for dette arbejde

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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.

TidsskriftEuropean Journal of Neurology
Udgave nummer1
Sider (fra-til)247-256
StatusUdgivet - jan. 2022

Bibliografisk note

Funding Information:
Friedemann Paul has received honoraria from advisory boards, travel support, speaking fees and/or financial support for research activities from Bayer, Novartis, Biogen, Teva, Sanofi‐Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, Shire, German Research Council, Werth Stiftung of the City of Cologne, the German Ministry of Education and Research, the EU FP7 Framework Program, the Arthur Arnstein Foundation Berlin, the Guthy Jackson Charitable Foundation, and the National Multiple Sclerosis Society of the United States. He serves as academic editor for and Associate Editor for . None resulted in a conflict of interest. Filipe Cortes‐Figueiredo, Nete Munk Nielsen, Egon Stenager, Jesper Hallas and Kasper Bruun Kristensen have nothing to disclose. PLoS One Neurology, Neuroimmunology and Neuroinflammation

Funding Information:
A stipend to F.C.F. was paid by (reference PD/BD/114122/2015), and K.B.K. was funded by the Independent Research Fund Denmark (grant 8020‐00176B) and the Research Fund of the Region of Southern Denmark (grant 17/33580). Fundação para a Ciência e Tecnologia

Publisher Copyright:
© 2021 European Academy of Neurology.


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