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The safety profile of biologic therapies for juvenile idiopathic arthritis

Abstract

The treatment of juvenile idiopathic arthritis (JIA) has been revolutionized by the use of novel biologic agents that have much improved patients' short-term and, according to early evidence, long-term outcomes. Currently available biologic agents used to treat patients with JIA include tumor necrosis factor (TNF) blockers, various agents that target interleukin (IL)-1 and the IL-6 receptor, T-cell co-stimulation inhibitors and antibodies to B-lymphocyte antigen CD20. These agents are increasingly used early in the course of the disease (often in combination with other immunosuppressive medications) and often for long periods of time, as patients can be difficult to wean from their use. Safety concerns (especially the long-term effects of biologic therapy) are, therefore, being examined more closely. For instance, in 2009, the FDA issued a warning related to the development of malignancies in patients with JIA who had used anti-TNF medications for >2.5 years. In this Review, data related to the safety profile of all currently available biologic agents used to treat JIA are examined, with a particular focus on anti-TNF therapy, the most studied biologic agent for JIA. Safety issues that need further study, including the implementation of registries to monitor long-term drug safety, are also discussed.

Key Points

  • The short-term safety of biologic agents used to treat juvenile idiopathic arthritis (JIA) seems to be good, even when they are used in combination with other DMARDs

  • Most adverse events associated with short-term biologic therapy are related to injection-site or infusion reactions and common childhood infections

  • Opportunistic infections (including with Mycobacterium species) and development of autoimmune disease seem to be rare in patients with JIA who are treated with biologic agents

  • Individuals with JIA who are treated with biologic agents might have an increased risk of malignancies

  • Large registries of long-term data are necessary to monitor rare adverse effects (particularly the development of malignancies and autoimmune diseases) that can be associated with some biologic therapies

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P. J. Hashkes, Y. Uziel and R. M. Laxer contributed equally to all aspects of this manuscript.

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Correspondence to Philip J. Hashkes.

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P. J. Hashkes has received speakers bureau (honoraria) from Novartis, has received medication for research purposes from Regeneron and is a consultant for URL Pharma. Y. Uziel has received speakers bureau (honoraria) from Abbott and research support from Novartis. R. M. Laxer declares no competing interests.

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Hashkes, P., Uziel, Y. & Laxer, R. The safety profile of biologic therapies for juvenile idiopathic arthritis. Nat Rev Rheumatol 6, 561–571 (2010). https://doi.org/10.1038/nrrheum.2010.142

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