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Use of Immunomodulating Drugs and Risk of Cutaneous Melanoma: A Nationwide Nested Case-Control Study

Authors Berge LAM, Andreassen BK, Stenehjem JS, Heir T, Karlstad Ø, Juzeniene A, Ghiasvand R, Larsen IK, Green AC, Veierød MB, Robsahm TE

Received 29 July 2020

Accepted for publication 8 October 2020

Published 18 December 2020 Volume 2020:12 Pages 1389—1401


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Vera Ehrenstein

Leon Alexander Mclaren Berge,1– 3 Bettina Kulle Andreassen,1 Jo Steinson Stenehjem,1,2,4 Trond Heir,5,6 Øystein Karlstad,7 Asta Juzeniene,8 Reza Ghiasvand,1,9 Inger Kristin Larsen,10 Adele C Green,11,12 Marit Bragelien Veierød,2 Trude Eid Robsahm1,3

1Department of Research, Cancer Registry of Norway, Oslo, Norway; 2Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; 3Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; 4Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway; 5Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Oslo Ischemia Study, Oslo University Hospital, Oslo, Norway; 7Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway; 8Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; 9Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway; 10Department of Registration, Cancer Registry of Norway, Oslo, Norway; 11Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia; 12Molecular Oncology Unit, CRUK Manchester Institute, University of Manchester, Manchester, UK

Correspondence: Leon Alexander Mclaren Berge
Cancer Registry of Norway, Majorstuen, Oslo N-0304, Norway
Tel +47 99605034

Purpose: Cutaneous melanoma is among the fastest growing malignancies in Norway and ultraviolet radiation (UVR) exposure is the primary environmental risk factor. Immunomodulating drugs can increase skin photosensitivity and suppress immune responses, and by such mechanisms influence melanoma risk. We, therefore, aimed to examine the associations between use of immunomodulating drugs and melanoma risk, at a nationwide population level.
Patients and Methods: In the Cancer Registry of Norway, we identified all cases aged 18– 85 with a first primary cutaneous melanoma diagnosed in 2007– 2015 (n=12,106). These were matched to population controls from the Norwegian National Registry 1:10 (n=118,564), on sex and year of birth using risk set sampling. Information on prescribed drugs (2004– 2015) was obtained by linkage to the Norwegian Prescription Database (NorPD). Conditional logistic regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for associations between use of immunomodulating drugs (immunosuppressants and corticosteroids) and melanoma risk, adjusted for ambient UVR and other drug use.
Results: Compared with ≤ 1 prescription, use of ≥ 8 prescriptions of immunosuppressants was associated with increased risk of melanoma (RR 1.50, 95% CI 1.27, 1.77). Similar associations were found for subgroups of immunosuppressants: drugs typically prescribed to organ transplant recipients (OTRs) (RR 2.02, 95% CI 1.35, 3.03) and methotrexate (RR 1.27, 95% CI 1.04, 1.55). Similar results were found for high levels of cumulative doses and across all histological subtypes. Use of corticosteroids was not associated with melanoma risk.
Conclusion: We found a positive association between use of immunosuppressants and melanoma risk, with the highest risk seen for drugs prescribed to OTRs. Knowledge about this risk increase is important for physicians and users of these drugs, for intensified surveillance, awareness and cautious sun exposure.

Keywords: immunosuppressants, corticosteroids, melanoma, prescription drugs, pharmacoepidemiology, registry-based

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