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Melanoma Risk in Patients Treated With Biologic Therapy for Common Inflammatory DiseasesA Systematic Review and Meta-analysis

Educational Objective:
To examine whether biologic treatment of inflammatory bowel disease, rheumatoid arthritis, or psoriasis is associated with an increased risk of melanoma compared with conventional systemic therapy.
1 Credit CME
Key Points

Question  Are patients with inflammatory bowel disease, rheumatoid arthritis, and psoriasis who are treated with biologic therapies at a higher risk of melanoma compared with those treated with conventional systemic therapy?

Findings  In this systematic review and meta-analysis of 7 cohort studies comprising 34 029 biologic-treated and 135 370 biologic-naive, systemically treated patients, biologic-treated patients with inflammatory bowel disease, rheumatoid arthritis, and psoriasis had an increased risk of melanoma compared with those who received conventional systemic therapy, but the difference was not statistically significant.

Meaning  The findings suggest that a clinically meaningful increase in melanoma risk cannot be ruled out; further studies adjusting for key risk factors are required.

Abstract

Importance  Biologic therapies are widely prescribed immunomodulatory agents. There are concerns that compared with treatment with conventional systemic therapy, long-term biologic treatment for common immune-mediated inflammatory diseases, namely inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and psoriasis, may be associated with increased risk of melanoma.

Objective  To examine whether biologic treatment of IBD, RA, or psoriasis is associated with an increased risk of melanoma compared with conventional systemic therapy.

Data Sources  Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published from January 1, 1995, to February 7, 2019, for eligible studies.

Study Selection  Randomized clinical trials, cohort studies, and nested case-control studies quantifying the risk of melanoma in biologic-treated patients with IBD, RA, and psoriasis compared with patients treated with conventional systemic therapy were included.

Data Extraction and Synthesis  Two reviewers independently extracted key study characteristics and outcomes. Study-specific risk estimates were pooled, and random- and fixed-effects model meta-analyses were conducted. Heterogeneity was assessed using the I2 statistic. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed.

Main Outcomes and Measures  The pooled relative risk (pRR) of melanoma in biologic-treated patients with IBD, RA, and psoriasis compared with biologic-naive patients treated with conventional systemic therapy.

Results  Seven cohort studies comprising 34 029 biologic-treated patients and 135 370 biologic-naive patients treated with conventional systemic therapy were eligible for inclusion. Biologic treatment was positively associated with melanoma in patients with IBD (pRR, 1.20; 95% CI, 0.60-2.40), RA (pRR, 1.20; 95% CI, 0.83-1.74), or psoriasis (hazard ratio, 1.57; 95% CI, 0.61-4.09) compared with those who received conventional systemic therapy, but the differences were not statistically significant. Adjustment for other risk factors was absent from most studies.

Conclusions and Relevance  The findings suggest that clinically important increases in melanoma risk in patients treated with biologic therapy for common inflammatory diseases cannot be ruled out based on current evidence. However, further studies with large patient numbers that adjust for key risk factors are needed to resolve the issue of long-term safety of biologic therapy.

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Article Information

Accepted for Publication: March 21, 2020.

Corresponding Author: Shamarke Esse, MRes, Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Oxford Road, Room 1.725, Stopford Building, Manchester M13 9PT, United Kingdom (shamarke.esse@postgrad.manchester.ac.uk).

Published Online: May 20, 2020. doi:10.1001/jamadermatol.2020.1300

Author Contributions: Mr Esse had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Esse, Green.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Esse.

Obtained funding: Mason, Green, Warren.

Administrative, technical, or material support: Mason.

Supervision: Mason, Green, Warren.

Conflict of Interest Disclosures: Dr Mason reported receiving personal fees from Janssen, LEO Pharma, Lilly, and Novartis outside the submitted work. Dr Warren reported receiving grants from AbbVie, Almirall, Amgen, Celgene, Janssen, Lilly, LEO Pharma, Novartis, and Pfizer during the conduct of the study and receiving personal fees from AbbVie, Almirall, Amgen, Arena, Avillion, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi, and UCB outside the submitted work. No other disclosures were reported.

Funding/Support: Mr Esse is funded by a Psoriasis Association PhD studentship (reference ST3/17).

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Psoriasis Association.

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