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Long-Term Safety of Immunomodulators in Pediatric Inflammatory Diseases

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Abstract

The medical management of chronic inflammatory disorders in children, including mainly inflammatory bowel diseases and rheumatic diseases, has evolved dramatically over recent years with the advent of disease-modifying drugs such as immunomodulators and biological agents capable of interrupting the inflammatory cascade underlying these disorders. These agents are generally administered in patients who are refractory to conventional therapies. However, there is growing support that their use in the initial phases of these disorders, especially in pediatric patients, could interrupt and cease the inflammatory process. Thus, the aims of therapy have transitioned from symptomatic control to the achievement of deeper remission, including the healing of the inflammatory lesions combined with symptomatic remission. Therefore, more patients are currently receiving immunomodulators or biologics, frequently in addition to corticosteroids. Immunosuppression due to these therapies increases safety concerns, particularly regarding the risk of infections and malignancies. The available literature highlights how the combination of more than one of these therapies, especially if the combination includes corticosteroids, amplifies the risk of severe opportunistic infections. Otherwise, the infections described are mainly mild. Regarding malignancies, the overall risk associated with treatment appears non-significant in pediatric populations, but an appropriate benefit/risk assessment is recommended prior to the introduction of aggressive treatments such as immunomodulants and biologics. The background cancer risk related to the disease itself remains an issue. Protracted follow-up programs are needed, and the results from international multicenter registries are awaited to better understand the true risk related to therapy of these pediatric populations.

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Acknowledgments

F. Nuti, F. Civitelli, and S. Cucchiara declare no relevant conflicts of interest. No sources of funding were used to support the writing of this manuscript.

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  1. Department of Pediatrics and Pediatric Neuropsychiatry, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy

    Federica Nuti, Fortunata Civitelli & Salvatore Cucchiara

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Nuti, F., Civitelli, F. & Cucchiara, S. Long-Term Safety of Immunomodulators in Pediatric Inflammatory Diseases. Pediatr Drugs 16, 343–352 (2014). https://doi.org/10.1007/s40272-014-0084-2

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