Objective To determine whether tumour necrosis factor inhibitor (TNFi) use is associated with an increased rate of incident malignancy compared with no TNFi use in the treatment of juvenile idiopathic arthritis (JIA), paediatric inflammatory bowel disease (pIBD) and paediatric plaque psoriasis (pPsO).
Methods We performed a retrospective cohort study of administrative claims data from the USA from 2000 to 2014. Exposure to TNFi was considered permanent from the first observed exposure onward. The malignancy outcome was defined by diagnosis codes with evidence of cancer treatment. We calculated standardised incidence ratios (SIRs) comparing the observed number of malignancies to the expected numbers according to cancer surveillance data. We used multivariable Cox proportional hazards models to estimate adjusted HRs (aHRs) for incident malignancy.
Results We identified 15 598 children with TNFi use and 73 839 children with no TNFi use (30 703 and 121 801 person-years of follow-up, respectively). We identified 15 malignancies among children with TNFi use (SIR 2.9 (1.6 to 4.9)) and 42 malignancies among children without TNFi use (SIR 2.1 (1.5 to 2.9)). The aHR was 1.58 (0.88 to 2.85) for TNFi use versus no TNFi use. In pIBD, TNFi use with thiopurine use was associated with a higher SIR (6.0 (1.2 to 17.5)) compared with TNFi use without thiopurine use (2.5 (0.7 to 6.4)).
Conclusion Children diagnosed with JIA, pIBD and pPsO had an increased rate of malignancy compared with the general population, but treatment with TNFi did not appear to significantly further increase the risk compared with no TNFi use. More data are needed about the long-term risks of TNFi use.
- Juvenile Idiopathic Arthritis
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Handling editor Josef S Smolen
Contributors TB conceptualised and designed the study, acquired the data, interpreted the results, drafted the initial manuscript, and reviewed and revised the manuscript. FX analysed the data and critically reviewed the manuscript. LC acquired the data, analysed the data and critically reviewed the manuscript. DBH, RM and MMM interpreted the results and critically reviewed the manuscript. JDL conceptualised and designed the study, interpreted the results and critically reviewed the manuscript. KGS acquired the data, interpreted the results and critically reviewed the manuscript. JRC conceptualised and designed the study, acquired the data, interpreted the results and critically reviewed the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Funding This study was funded by the United States Agency for Healthcare Research and Quality (AHRQ) as part of a grant (no U19HS021110) administered through the AHRQ Center for Education and Research on Therapeutics Program.
Competing interests TB has received consulting fees from UCB, Genentech/Roche, Novartis, Bristol-Myers Squibb and Sobi. JDL has received consulting fees from Takeda, Pfizer, Lilly, Gilead, Johnson & Johnson, Samsung Bioepis, AbbVie, UCB and Merck; and research funding from Takeda. RM has received consulting fees from Takeda. KGS has received consulting fees from Abbot, Amgen, Ardea/AstraZeneca, BMS, Crealta, Lilly, Merck, Pfizer and Genentech/Roche; and research funding from Amgen, Ardea/AstraZeneca, Crealta, Lilly, Merck and Takeda. JRC has received consulting fees from Genentech/Roche, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo and AbbVie; and research funding from Genentech/Roche, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo and AbbVie.
Ethics approval We obtained ethics approval from the Institutional Review Board of the University of Alabama at Birmingham, protocol number X140507011.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The MAX files and MarketScan files cannot be shared according to the terms of the data use agreements.
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