The effects of TNF-alpha inhibitor therapy on the incidence of infection in JIA children: a meta-analysis

Abstract

BackgroundJuvenile Idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The diagnosis is based on the underlying symptoms of arthritis with an exclusion of other diseases Biologic agents are increasingly used on the side of disease-modifying anti-rheumatic drugs (DMARD) in JIA treatment.Main bodyThe aim of this meta-analysis was to investigate the observed infections in JIA children during tumor necrosis factor (TNF)-alpha inhibitor therapy. A systematic search of three databases (Medline via PubMed, Embase, Cochrane Library) was carried out up to May 2018. Published trials that evaluated the infectious adverse events in patients receiving TNF-alpha inhibitor vs. a control group were included in the analysis. Full-text data extraction was carried out independently by the investigators from ten relevant publications. 1434 patients received TNF-alpha inhibitor therapy; the control group consisted of 696 subjects. The analysis presented the risk of infection in the active treatment group (OR = 1.13; 95% CI: 0.76–1.69; p = 0.543). The majority of infections were upper respiratory tract infections (URTIs). Furthermore, the subgroup analysis demonstrated a higher infection rate in the observed localization.ConclusionAnti-TNF therapy slightly but not significantly increases the incidence of infection in JIA children compared to other therapies (GRADE: moderate evidence). The most common infections reported were mild URTIs. Further studies with larger patients number with a strong evidence level are crucially needed to finalize the answer whether anti-TNF therapy elevates and if yes on what extent the incidence of infection in JIA children.Trial registrationProspero: CRD42017067873.Electronic supplementary materialThe online version of this article (10.1186/s12969-019-0305-x) contains supplementary material, which is available to authorized users.

Pneumococcal vaccine in patients with idiopathic juvenile arthritis in treatment with tumor necrosis factor inhibitors

“…A lymphopenia less than 600/mL, but even less than 250 CD4 LT/mL and treatment with glucocorticoids in doses of more than 10 mg of prednisolone or its equivalent per day are more frequently associated with infections. 10,22 The lower lymphocyte count with a correlation of significance close to 5% and the response of specific antibodies to serotype 4 among non-responders in our study make it necessary to directly corroborate and/or assess response to pneumococcal vaccine in lymphopenic patients or those with low lymphocyte count below the cut-off point.…”

“…In parallel, the increased risk of infections associated with the use of glucocorticoids has been demonstrated widely, especially in lymphopenic patients, but there are no data regarding its role in response to pneumococcal vaccines. 10,12 Patients receiving chronic immunosuppressive therapy with glucocorticoids and/or DMARDs can develop severe lymphopenia, involving all types of lymphocytes. A lymphopenia less than 600/mL, but even less than 250 CD4 LT/mL and treatment with glucocorticoids in doses of more than 10 mg of prednisolone or its equivalent per day are more frequently associated with infections.…”

“…9 JIA patients, because of immunosuppression, are at increased risk of reactivation of tuberculosis, chickenpox, and infections by capsulated bacteria. 10 Preventive vaccination helps to decrease these aforementioned risks. 11 Various publications have demonstrated the safety and efficacy of different vaccines in patients with rheumatological diseases, in spite of the use of immunosuppressants.…”

Peripheral Blood Lymphocyte Analysis in Oligo- and Polyarticular Juvenile Idiopathic Arthritis Patients Receiving Methotrexate or Adalimumab Therapy: A Cross-Sectional Study

“…The study reported that the majority of infections were located in the upper respiratory tract. Yet, significant increase in the infection rate could not be detected ( 27 ). Beukelman et al reported that steroid-sparing DMARD therapies may reduce the risk of severe infections in children since high-dose steroid therapy may increase the infection rate 3-fold in JIA patients ( 25 , 26 ).…”

“…To date, our results demonstrated for the first time that CD56 NK-cells were significantly decreased in the MTX/ADA group compared to healthy controls. It might be an explanation of the increased number of mild, viral, upper respiratory tract infections demonstrated in various trials ( 27 ). Other parts of the innate immune-system like complements and phagocyte levels did not show any alteration.…”