TY - JOUR
T1 - Cumulative incidence and risk of infection in patients with rheumatoid arthritis treated with janus kinase inhibitors
T2 - A systematic review and meta-analysis
AU - Ouranos, Konstantinos
AU - Avila, Diana V.
AU - Mylona, Evangelia K.
AU - Vassilopoulos, Athanasios
AU - Vassilopoulos, Stephanos
AU - Shehadeh, Fadi
AU - Mylonakis, Eleftherios
N1 - Publisher Copyright:
© 2024 Ouranos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2024/7
Y1 - 2024/7
N2 - 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.
AB - 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.
KW - Arthritis, Rheumatoid/drug therapy
KW - Humans
KW - Janus Kinase Inhibitors/adverse effects
KW - Azetidines/adverse effects
KW - Incidence
KW - Purines/adverse effects
KW - Pyrazoles/adverse effects
KW - Pyrimidines/adverse effects
KW - Piperidines/adverse effects
KW - Sulfonamides/adverse effects
KW - Herpes Zoster/epidemiology
KW - Opportunistic Infections/epidemiology
KW - Pyrroles/adverse effects
KW - Niacinamide/analogs & derivatives
KW - Infections/epidemiology
KW - Randomized Controlled Trials as Topic
KW - Heterocyclic Compounds, 3-Ring/adverse effects
KW - Antirheumatic Agents/adverse effects
KW - Triazoles/adverse effects
KW - Adamantane/analogs & derivatives
KW - Pyridines
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U2 - 10.1371/journal.pone.0306548
DO - 10.1371/journal.pone.0306548
M3 - Article
C2 - 39083492
SN - 1932-6203
VL - 19
JO - PLoS ONE
JF - PLoS ONE
IS - 7 July
M1 - e0306548
ER -