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Meta-Analysis
. 2024 Jul 31;19(7):e0306548.
doi: 10.1371/journal.pone.0306548. eCollection 2024.

Cumulative incidence and risk of infection in patients with rheumatoid arthritis treated with janus kinase inhibitors: A systematic review and meta-analysis

Konstantinos Ouranos  1 , Diana V Avila  1 , Evangelia K Mylona  1 , Athanasios Vassilopoulos  2 , Stephanos Vassilopoulos  2 , Fadi Shehadeh  1   3 , Eleftherios Mylonakis  1   4
Affiliations
Meta-Analysis

Cumulative incidence and risk of infection in patients with rheumatoid arthritis treated with janus kinase inhibitors: A systematic review and meta-analysis

Konstantinos Ouranos et al. PLoS One. .

Abstract

Patients with rheumatoid arthritis (RA) who receive immunosuppressive medications have a heightened risk of infection. The goal of our study was to calculate the pooled cumulative incidence and risk of infection in patients with RA treated with Janus kinase inhibitors (JAKi). The PubMed and EMBASE databases were queried for randomized controlled trials comparing patients with RA treated with JAKi (upadacitinib, baricitinib, tofacitinib, peficitinib, or filgotinib), defined as the treatment group, compared with control subjects, defined as participants receiving placebo or treatment regimen that was similar to that of participants in the treatment group, with the exception of JAKi. The primary study endpoint was the relative risk (RR) of any-grade and severe infection. The secondary endpoints were RR and cumulative incidence of opportunistic infections, herpes zoster, and pneumonia. The Stata v17 software was used for all data analysis. Results showed that treatment with baricitinib was associated with an increased risk of any-grade (RR 1.34; 95% CI: 1.19-1.52) and opportunistic (RR 2.69; 95% CI: 1.22-5.94) infection, whereas treatment with filgotinib (RR 1.21; 95% CI: 1.05-1.39), peficitinib (RR 1.40; 95% CI: 1.05-1.86) and upadacitinib (RR 1.30; 95% CI: 1.09-1.56) was associated with increased risk of any-grade infection only. Analysis based on type of infection showed a pooled cumulative incidence of 32.44% for any-grade infections, 2.02% for severe infections, 1.74% for opportunistic infections, 1.56% for herpes zoster, and 0.49% for pneumonia in patients treated with any JAKi during the follow-up period. Treatment with specific JAKi in patients with RA is associated with an increased risk of any-grade and opportunistic infections but not severe infection. Close clinical monitoring of patients with RA treated with JAKi is required to establish the long-term infection risk profile of these agents.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flowchart outlining the selection process for studies included in the analysis.
Fig 2
Fig 2. Relative risk of any-grade infection in patients with RA treated with JAKi compared with control subjects.
The size of the square is representative of the weight assigned to the respective study for outcome analysis. The 95% CI for each study is represented by the horizontal lines. The diamond shape represents the pooled estimate of the analysis. Abbreviations: CI: confidence interval; JAKi: Janus-activated kinase inhibitor; RA: rheumatoid arthritis; RR: relative risk.
Fig 3
Fig 3. Relative risk of severe infection in patients with RA treated with JAKi compared with control subjects.
The size of the square is representative of the weight assigned to the respective study for outcome analysis. The 95% CI for each study is represented by the horizontal lines. The diamond shape represents the pooled estimate of the analysis. Abbreviations: CI: confidence interval; JAKi: Janus-activated kinase inhibitor; RA: rheumatoid arthritis; RR: relative risk.
Fig 4
Fig 4. Relative risk of opportunistic infections in patients with RA treated with JAKi compared with control subjects.
The size of the square is representative of the weight assigned to the respective study for outcome analysis. The 95% CI for each study is represented by the horizontal lines. The diamond shape represents the pooled estimate of the analysis. Abbreviations: CI: confidence interval; JAKi: Janus-activated kinase inhibitor; RA: rheumatoid arthritis; RR: relative risk.
Fig 5
Fig 5. Relative risk of herpes zoster in patients with RA treated JAKi compared with control subjects.
The size of the square is representative of the weight assigned to the respective study for outcome analysis. The 95% CI for each study is represented by the horizontal lines. The diamond shape represents the pooled estimate of the analysis. Abbreviations: CI: confidence interval; JAKi: Janus-activated kinase inhibitor; RA: rheumatoid arthritis; RR: relative risk.
Fig 6
Fig 6. Relative risk of pneumonia in patients with RA treated with JAKi compared with control subjects.
The size of the square is representative of the weight assigned to the respective study for outcome analysis. The 95% CI for each study is represented by the horizontal lines. The diamond shape represents the pooled estimate of the analysis. Abbreviations: CI: confidence interval; JAKi: Janus-activated kinase inhibitor; RA: rheumatoid arthritis; RR: relative risk.
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References

    1. Tanaka Y. Recent progress in treatments of rheumatoid arthritis: an overview of developments in biologics and small molecules, and remaining unmet needs. Rheumatology (Oxford). 2021;60: vi12–vi20. doi: 10.1093/rheumatology/keab609 - DOI - PMC - PubMed
    1. Smolen JS, Landewé RBM, Bergstra SA, Kerschbaumer A, Sepriano A, Aletaha D, et al.. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82: 3–18. doi: 10.1136/ard-2022-223356 10.1136/ard-2022-223356 - DOI - DOI - PubMed
    1. Fraenkel L, Bathon JM, England BR, St Clair EW, Arayssi T, Carandang K, et al.. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2021;73: 1108–1123. doi: 10.1002/art.41752 - DOI - PubMed
    1. Shams S, Martinez JM, Dawson JRD, Flores J, Gabriel M, Garcia G, et al.. The Therapeutic Landscape of Rheumatoid Arthritis: Current State and Future Directions. Front Pharmacol. 2021;12: 680043. doi: 10.3389/fphar.2021.680043 - DOI - PMC - PubMed
    1. Angelini J, Talotta R, Roncato R, Fornasier G, Barbiero G, Dal Cin L, et al.. JAK-Inhibitors for the Treatment of Rheumatoid Arthritis: A Focus on the Present and an Outlook on the Future. Biomolecules. 2020;10: 1002. doi: 10.3390/biom10071002 - DOI - PMC - PubMed

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