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
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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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