Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jan 18;17(1):4.
doi: 10.1186/s12969-019-0305-x.

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

Arnold Nagy  1 , Péter Mátrai  2 , Péter Hegyi  3   4   5 , Hussain Alizadeh  6 , Judit Bajor  7 , László Czopf  8 , Zoltán Gyöngyi  9 , Zoltán Kiss  10 , Katalin Márta  3   3 , Mária Simon  11 , Ágnes Lilla Szilágyi  12 , Gábor Veres  13   14 , Bernadett Mosdósi  15
Affiliations
Review

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

Arnold Nagy et al. Pediatr Rheumatol Online J. .

Abstract

Background: Juvenile 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 body: The 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.

Conclusion: Anti-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 registration: Prospero: CRD42017067873 .

Keywords: DMARD; Infection; JIA; Placebo; TNF-alpha inhibitor.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of the articles included
Fig. 2
Fig. 2
The risk of infection between the TNF-alpha inhibitor and the non-TNF-alpha inhibitor group. The size of the grey marker is proportional to the weight of the study. (OR = 1.13; 95% CI: 0.76–1.69; p = 0.543)
Fig. 3
Fig. 3
Forest plot on the occurrence of upper respiratory tract infection in the TNF-alpha inhibitor group vs. the control group. The risk of URTI is elevated in the former group (OR = 1.10; 95% CI: 0.65–1.84; p = 0.729)
Fig. 4
Fig. 4
Effect of the TNF-alpha inhibitor group vs. the control group on the occurrence of the infectious diseases demonstrated. An increase (with exception of gastrointestinal tract infections) was observed in the risk of a particular infection in the TNF-alpha inhibitor group
See this image and copyright information in PMC

References

    1. Merino R, de Inocencio J, Garcia-Consuegra J. Evaluation of revised international league of associations for Rheumatology classification criteria for juvenile idiopathic arthritis in Spanish children (Edmonton 2001) J Rheumatol. 2005;32(3):559–561. - PubMed
    1. Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, DeWitt EM, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken). 2011;63(4):465–482. doi: 10.1002/acr.20460. - DOI - PMC - PubMed
    1. Sterba Y, Ilowite N. Biologics in Pediatric Rheumatology: Quo Vadis? Curr Rheumatol Rep. 2016;18(7):45. doi: 10.1007/s11926-016-0593-9. - DOI - PubMed
    1. Lovell DJ, Reiff A, Ilowite NT, Wallace CA, Chon Y, Lin SL, et al. Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Arthritis Rheum. 2008;58(5):1496–1504. doi: 10.1002/art.23427. - DOI - PubMed
    1. Lahdenne P, Vahasalo P, Honkanen V. Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study. Ann Rheum Dis. 2003;62(3):245–247. doi: 10.1136/ard.62.3.245. - DOI - PMC - PubMed

Substances