Long-Term Safety of Immunomodulators in Pediatric Inflammatory Diseases

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.

The European Hematology Association Roadmap for European Hematology Research: a consensus document

“…Infections associated with biologics: biological agents, particularly monoclonal antibodies to proinflammatory cytokines, are being widely used, increasing the risk of infections in a high-risk population: 343 1. More information regarding specific infectious risks of this family of agents would be useful to allow appropriate prophylaxis to be instituted.…”

Vaccination coverage in children with juvenile idiopathic arthritis, inflammatory bowel diseases, and healthy peers: Cross-sectional electronic survey data

“…Patients with immune-mediated diseases, such as juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD), are at increased risk of developing infections, due to disease-related immune dysfunction and applying of immunosuppressive drugs[ 1 , 2 ]. Additional factors of increased infection risk include disease activity, malnutrition, surgical interventions, and concomitant chronic diseases, such as obesity, diabetes mellitus, atopic dermatitis, asthma, and others[ 3 - 5 ].…”

Vaccines in Children with Inflammatory Bowel Disease: Brief Review

“…Children with IBDs have a dysfunctional immune system. Moreover, in order to reduce clinical manifestation of IBDs, they are frequently treated with immunomodulating drugs and biological therapy [ 7 ], which significantly impair immune system functions and lead to an increased risk of infections [ 8 , 9 , 10 ]. Vaccines are essential to prevent at least part of these infections, and this explains why strict compliance to the immunization guidelines specifically prepared for IBD patients is strongly recommended by health authorities worldwide.…”