Biological therapy and development of neoplastic disease in patients with juvenile rheumatic disease: a systematic review

Abstract

Juvenile rheumatic diseases affect the musculoskeletal system and begin before the age of 18. These conditions have varied, identifiable or unknown etiologies, but those of an autoimmune inflammatory nature have been associated with an increased risk of development of cancer, regardless of treatment. This study aims to assess, through a systematic review of the literature according to Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) quality criteria, the risk of cancer in patients with juvenile rheumatic disease, and its association with biological agents. The criteria described by the Strengthening the Reporting of Observational Studies in Epidemiology initiative were used in order to assess the methodological quality of those individual items selected in this study. We analyzed nine publications, from a total of 251 papers initially selected. There was an increase in cancer risk in the population with juvenile rheumatic disease versus the general population. Most specified cancers were of a lymphoproliferative nature. Seven studies did not specify the treatment or not defined an association between treatment and cancer risk. Only one study has suggested this association; in it, their authors observed high risk in patients diagnosed in the last 20 years, a period of the advent of new therapies. One study found an increased risk in a population not treated with biological agents, suggesting a disease in its natural course, and not an adverse effect of therapy. Studies have shown an increased risk of malignancy associated with juvenile rheumatic disease, and this may be related to disease activity and not specifically to the treatment with biological agents.

A controversial topic in juvenile idiopathic arthritis: Association between biologic agents and malignancy

“…10 The report was criticized methodologically and led to the emergence of studies addressing the issue. 9,11,12 Furthermore, it was challenging to interpret the data in terms of low incidence and prevalence of both JIA and malignancy in children, the lack of knowledge of the underlying frequency of specific neoplasms in untreated JIA, and unknown contribution of concomitant immunosuppressive medications. 13,14 Although a clear relationship could not be established with the contradictory study results, there are ongoing concerns on the longterm safety data and side-effect profiles of the drugs.…”

“…In 2008, the Food and Drug Administration (FDA) called attention to the association between the use of TNF inhibitors and malignancy 10 . The report was criticized methodologically and led to the emergence of studies addressing the issue 9,11,12 . Furthermore, it was challenging to interpret the data in terms of low incidence and prevalence of both JIA and malignancy in children, the lack of knowledge of the underlying frequency of specific neoplasms in untreated JIA, and unknown contribution of concomitant immunosuppressive medications 13,14 …”