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Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers
  1. Louise K Mercer1,
  2. Johan Askling2,3,
  3. Pauline Raaschou2,
  4. William G Dixon1,
  5. Lene Dreyer4,5,
  6. Merete Lund Hetland6,
  7. Anja Strangfeld7,
  8. Angela Zink7,8,
  9. Xavier Mariette9,
  10. Axel Finckh10,
  11. Helena Canhao11,
  12. Florenzo Iannone12,
  13. Jakub Zavada13,14,
  14. Jacques Morel15,
  15. Jacques-Eric Gottenberg16,
  16. Kimme L Hyrich1,17,
  17. Joachim Listing7
  1. 1Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
  2. 2Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  3. 3Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  4. 4Department of Rheumatology, Herlev and Gentofte University Hospital, Hellerup, Denmark
  5. 5The Parker Institute, Bispebjerg and Frederiksberg, University of Copenhagen, Copenhagen, Denmark
  6. 6The DANBIO registry and Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet Glostrup and second affiliation Hetland: Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  7. 7Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany
  8. 8Charité University Medicine Berlin, Berlin, Germany
  9. 9Rheumatology Department, Université Paris-Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France
  10. 10Rheumatology Division, University of Geneva, Geneva, Switzerland
  11. 11Rheumatology Research Unit, Rheumatology Department, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon Portugal, CHLN- Santa Maria Hospital, CAML, Lisbon, Portugal
  12. 12Rheumatology Unit—DIM, University of Bari, Bari, Italy
  13. 13Institute of Rheumatology, Prague, Czech Republic
  14. 14First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
  15. 15Department of Rheumatology, Teaching Hospital of Lapeyronie and University of Montpellier, Montpellier, France
  16. 16Rheumatology Department, National Center for Rare Systemic Autoimmune Diseases, Hôpitaux Universitaires de Strasbourg, CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunopathologie et Chimie Thérapeutique/Laboratory of Excellence Medalis, Université de Strasbourg, Strasbourg, France
  17. 17NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester Partnership, Manchester, UK
  1. Correspondence to Dr Joachim Listing, Deutsches Rheuma-Forschungszentrum Berlin, Ein Leibniz Institut, Programmbereich Epidemiologie, Charitéplatz 1, Berlin 10117, Germany; Listing{at}drfz.de

Abstract

Objectives Some studies have reported a possible association between exposure to tumour necrosis factor (TNF) inhibitors and an increased risk of melanoma. The aim of this study was to investigate the incidence of invasive cutaneous melanomas in patients with rheumatoid arthritis (RA) treated with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy.

Methods Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country-specific general population of each register as reference, age, sex and calendar year standardised incidence ratios (SIRs) of invasive histology-confirmed cutaneous melanoma were calculated within each register. Pooled SIR and incidence rate ratios (IRRs) comparing biologic cohorts to biologic-naïve were calculated across countries by taking the size of the register into account.

Results Overall 130 315 RA patients with a mean age of 58 years contributing 579 983 person-years were available for the analysis and 287 developed a first melanoma. Pooled SIRs for biologic-naïve, TNFi and rituximab-exposed patients were 1.1 (95% CI 0.9 to 1.4), 1.2 (0.99 to 1.6) and 1.3 (0.6 to 2.6), respectively. Incidence rates in tocilizumab and abatacept-exposed patients were also not significantly increased. IRR versus biologic-naïve patients were: TNFi 1.1 (95% CI 0.8 to 1.6); rituximab 1.2 (0.5 to 2.9).

Conclusions This large European collaborative project did not confirm an overall increased risk of melanoma following exposure to TNFi.

  • Rheumatoid Arthritis
  • Anti-TNF
  • Epidemiology

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Handling editor Tore K Kvien

  • Twitter Follow William Dixon at @WGDixon

  • Contributors Study concept and design: LKM and JL. Acquisition of the data and critical revision of the manuscript for important intellectual content: LKM, JA, PR, WGD, LD, MLH, AS, AZ, XM, AF, HC, FI, JZ, JM, J-EG, KLH and JL. Drafting the manuscript: LKM and JL.

  • Funding Individual registries were funded by pharmaceutical companies (AbbVie, BMS, MSD, Pfizer, Roche, UCB). The pharmaceutical companies funding these registers were, however, not involved in the planning of the project, the statistical analyses or the interpretation of the results.

  • Competing interests JA received grant/research support from AstraZeneca, Merck, Lilly and Pfizer, and has received grant support from Abbvie, Pfizer, Merck, Roche, BMS and UCB for the ARTIS register. LD has received speaking fees from UCB and MSD. AS received speakers fees (<$10 000) from BMS, MSD, Pfizer, Roche, Sanofi-Aventis. AZ received grant/research support from Abbvie, Amgen, BMS, MSD, Roche, Pfizer and UCB for the German biologics register RABBIT and speakers fees (<$10 000) from BMS, MSD, Novartis, Pfizer, Roche, Sanofi and UCB. XM received honorarium (<$10 000) from BMS, Pfizer and UCB. AF received honorarium (<$10 000) from Abbvie, BMS, Pfizer, Roche and UCB. FI received personal fees from Actelion, Celgene, Janssen, Pfizer, AbbVie, UCB and MSD outside the submitted work. JZ received honorarium (<$10 000) from Abbvie and Hospira. JM received <$10 000 for honoraria and consultancies from Roche. J-EG received honorarium (<$10 000) from Abbvie, BMS, MSD, Pfizer, Roche and UCB. KLH received grant/research support from Pfizer and honoraria (<$10 000) from Abbvie and Pfizer. JL received honoraria (<$10 000) from Novartis-Sandoz and Pfizer.

  • Patient consent Obtained.

  • Ethics approval Each register was given approval by their local ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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