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

Arnold Nagy¹, Péter Mátrai², Péter Hegyi^{3

4

5}, Hussain Alizadeh⁶, Judit Bajor⁷, László Czopf⁸, Zoltán Gyöngyi⁹, Zoltán Kiss¹⁰, Katalin Márta^{3

3}, Mária Simon¹¹, Ágnes Lilla Szilágyi¹², Gábor Veres^{13

14}, Bernadett Mosdósi¹⁵

Affiliations

¹ Department of Paediatrics, Medical School, University of Pécs, 7. József Attila street, Pécs, 7623, Hungary. nagy.arnold@pte.hu.
² Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary.
³ Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁴ Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁵ Momentum Gastroenterology Multidisciplinary Research Group, Hungarian Academy of Sciences - University of Szeged, Szeged, Hungary.
⁶ Division of Haematology, First Department of Internal Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁷ Division of Gastroenterology, First Department of Internal Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁸ Division of Cardiology, First Department of Internal Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁹ Department of Public Health Medicine, Medical School, University of Pécs, Pécs, Hungary.
¹⁰ First Department of Paediatrics, Semmelweis University, Budapest, Hungary.
¹¹ Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary.
¹² Department of Psychiatry and Psychotherapy, Medical School, University of Pécs, Pécs, Hungary.
¹³ Institute of Surgical Research, University of Szeged, Szeged, Hungary.
¹⁴ Department of Paediatrics, Medical School, University of Debrecen, Debrecen, Hungary.
¹⁵ Department of Paediatrics, Medical School, University of Pécs, 7. József Attila street, Pécs, 7623, Hungary.

PMID: 30658717
PMCID: PMC6339290
DOI: 10.1186/s12969-019-0305-x

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. 2019.

. 2019 Jan 18;17(1):4.

doi: 10.1186/s12969-019-0305-x.

Authors

Affiliations

¹ Department of Paediatrics, Medical School, University of Pécs, 7. József Attila street, Pécs, 7623, Hungary. nagy.arnold@pte.hu.
² Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary.
³ Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁴ Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁵ Momentum Gastroenterology Multidisciplinary Research Group, Hungarian Academy of Sciences - University of Szeged, Szeged, Hungary.
⁶ Division of Haematology, First Department of Internal Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁷ Division of Gastroenterology, First Department of Internal Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁸ Division of Cardiology, First Department of Internal Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁹ Department of Public Health Medicine, Medical School, University of Pécs, Pécs, Hungary.
¹⁰ First Department of Paediatrics, Semmelweis University, Budapest, Hungary.
¹¹ Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary.
¹² Department of Psychiatry and Psychotherapy, Medical School, University of Pécs, Pécs, Hungary.
¹³ Institute of Surgical Research, University of Szeged, Szeged, Hungary.
¹⁴ Department of Paediatrics, Medical School, University of Debrecen, Debrecen, Hungary.
¹⁵ Department of Paediatrics, Medical School, University of Pécs, 7. József Attila street, Pécs, 7623, Hungary.

PMID: 30658717
PMCID: PMC6339290
DOI: 10.1186/s12969-019-0305-x

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.

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The authors declare that they have no competing interests.

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Figures

**Fig. 1**
Flowchart of the articles included

**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**
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**
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

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