Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers.
OBJECTIVE
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.
Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
Louise K
LK
Mercer
Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
Johan
J
Askling
Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Pauline
P
Raaschou
Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
William G
http://orcid.org/0000-0001-5881-4857
WG
Dixon
Department of Rheumatology, Herlev and Gentofte University Hospital, Hellerup, Denmark.|The Parker Institute, Bispebjerg and Frederiksberg, University of Copenhagen, Copenhagen, Denmark.
Lene
L
Dreyer
The 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.
Merete Lund
ML
Hetland
Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany.
Anja
A
Strangfeld
Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany.|Charité University Medicine Berlin, Berlin, Germany.
Angela
A
Zink
Rheumatology 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.
Xavier
X
Mariette
Rheumatology Division, University of Geneva, Geneva, Switzerland.
Axel
A
Finckh
Rheumatology Research Unit, Rheumatology Department, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon Portugal, CHLN- Santa Maria Hospital, CAML, Lisbon, Portugal.
Helena
H
Canhao
Rheumatology Unit-DIM, University of Bari, Bari, Italy.
Florenzo
F
Iannone
Institute of Rheumatology, Prague, Czech Republic.|First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
Jakub
J
Zavada
Department of Rheumatology, Teaching Hospital of Lapeyronie and University of Montpellier, Montpellier, France.
Jacques
J
Morel
Rheumatology 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.
Jacques-Eric
JE
Gottenberg
Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.|NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester Partnership, Manchester, UK.
Kimme L
http://orcid.org/0000-0001-8242-9262
KL
Hyrich
Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany.
Joachim
J
Listing
D000069594:Abatacept / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008545:Melanoma / Q000453:epidemiology*; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D000069283:Rituximab / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000453:epidemiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000069594:Abatacept; C502936:tocilizumab
Anti-TNF; Epidemiology; Rheumatoid Arthritis