The incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents: A systematic review and meta-analysis

Background: Biologic (bDMARD) and targeted synthetic (tsDMARD) disease-modifying anti-rheumatic drugs have broadened the treatment options and are increasingly used for patients with psoriatic arthritis (PsA). These agents block different pro-inflammatory cytokines or specific intracellular signalin...

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Main Authors: Athanasios Vassilopoulos, Fadi Shehadeh, Gregorio Benitez, Markos Kalligeros, Joanne S. Cunha, Cheston B. Cunha, Eleftherios Mylonakis
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.992713/full
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author Athanasios Vassilopoulos
Athanasios Vassilopoulos
Fadi Shehadeh
Fadi Shehadeh
Fadi Shehadeh
Gregorio Benitez
Gregorio Benitez
Markos Kalligeros
Markos Kalligeros
Joanne S. Cunha
Cheston B. Cunha
Cheston B. Cunha
Eleftherios Mylonakis
Eleftherios Mylonakis
author_facet Athanasios Vassilopoulos
Athanasios Vassilopoulos
Fadi Shehadeh
Fadi Shehadeh
Fadi Shehadeh
Gregorio Benitez
Gregorio Benitez
Markos Kalligeros
Markos Kalligeros
Joanne S. Cunha
Cheston B. Cunha
Cheston B. Cunha
Eleftherios Mylonakis
Eleftherios Mylonakis
author_sort Athanasios Vassilopoulos
collection DOAJ
description Background: Biologic (bDMARD) and targeted synthetic (tsDMARD) disease-modifying anti-rheumatic drugs have broadened the treatment options and are increasingly used for patients with psoriatic arthritis (PsA). These agents block different pro-inflammatory cytokines or specific intracellular signaling pathways that promote inflammation and can place patients at risk of serious infections. We aimed to review the incidence of opportunistic infections (OIs) in patients with PsA who were treated with these agents.Methods: We searched PubMed and EMBASE through 14 April 2022 for randomized clinical trials evaluating bDMARD or tsDMARD in the treatment of PsA. Trials were eligible if they compared the effect of a bDMARD or tsDMARD with placebo and provided safety data. We used the Revised Cochrane risk-of-bias tool to assess the risk of bias among trials, and stratified the studies by mechanism of action (MOA) of the agents studied.Results: We included 47 studies in this analysis. A total of 17,197 patients received at least one dose of an agent of interest. The cumulative incidence of OIs by MOA was as follows: 1) JAK inhibitors: 2.72% (95% CI: 1.05%–5.04%), 2) anti-IL-17: 1.18% (95% CI: 0.60%–1.9%), 3) anti-IL-23: 0.24% (95% CI: 0.04%–0.54%), and 4) anti-TNFs: 0.01% (95% CI: 0.00%–0.21%). Based on their MOA, these agents are known to increase the risk of certain serious infections. The cumulative incidence of herpes zoster infection following treatment with JAK inhibitors (JAKi) was 2.53% (95% CI: 1.03%–4.57%) and the cumulative incidence of opportunistic Candida spp. infections following treatment with anti-IL-17, was 0.97% (95% CI: 0.51%–1.56%).Conclusion: The overall incidence of OIs among patients with PsA who were treated with biologic and targeted synthetic agents is low. However, careful monitoring is warranted for specific OIs such as herpes zoster infection following JAKi treatment, mucocutaneous candidiasis following anti-IL-17 treatment, and Mycobacterium tuberculosis infection following anti-TNF treatment.
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spelling doaj.art-9334775f7e744409af189e50a7fe5eb82022-12-22T02:31:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.992713992713The incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents: A systematic review and meta-analysisAthanasios Vassilopoulos0Athanasios Vassilopoulos1Fadi Shehadeh2Fadi Shehadeh3Fadi Shehadeh4Gregorio Benitez5Gregorio Benitez6Markos Kalligeros7Markos Kalligeros8Joanne S. Cunha9Cheston B. Cunha10Cheston B. Cunha11Eleftherios Mylonakis12Eleftherios Mylonakis13Infectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesSchool of Electrical and Computer Engineering, National Technical University of Athens, Athens, GreeceInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesBackground: Biologic (bDMARD) and targeted synthetic (tsDMARD) disease-modifying anti-rheumatic drugs have broadened the treatment options and are increasingly used for patients with psoriatic arthritis (PsA). These agents block different pro-inflammatory cytokines or specific intracellular signaling pathways that promote inflammation and can place patients at risk of serious infections. We aimed to review the incidence of opportunistic infections (OIs) in patients with PsA who were treated with these agents.Methods: We searched PubMed and EMBASE through 14 April 2022 for randomized clinical trials evaluating bDMARD or tsDMARD in the treatment of PsA. Trials were eligible if they compared the effect of a bDMARD or tsDMARD with placebo and provided safety data. We used the Revised Cochrane risk-of-bias tool to assess the risk of bias among trials, and stratified the studies by mechanism of action (MOA) of the agents studied.Results: We included 47 studies in this analysis. A total of 17,197 patients received at least one dose of an agent of interest. The cumulative incidence of OIs by MOA was as follows: 1) JAK inhibitors: 2.72% (95% CI: 1.05%–5.04%), 2) anti-IL-17: 1.18% (95% CI: 0.60%–1.9%), 3) anti-IL-23: 0.24% (95% CI: 0.04%–0.54%), and 4) anti-TNFs: 0.01% (95% CI: 0.00%–0.21%). Based on their MOA, these agents are known to increase the risk of certain serious infections. The cumulative incidence of herpes zoster infection following treatment with JAK inhibitors (JAKi) was 2.53% (95% CI: 1.03%–4.57%) and the cumulative incidence of opportunistic Candida spp. infections following treatment with anti-IL-17, was 0.97% (95% CI: 0.51%–1.56%).Conclusion: The overall incidence of OIs among patients with PsA who were treated with biologic and targeted synthetic agents is low. However, careful monitoring is warranted for specific OIs such as herpes zoster infection following JAKi treatment, mucocutaneous candidiasis following anti-IL-17 treatment, and Mycobacterium tuberculosis infection following anti-TNF treatment.https://www.frontiersin.org/articles/10.3389/fphar.2022.992713/fullpsoriatic arthritisopportunistic infectionsBDMARDstsDMARDsJAK inhibitorsherpes zoster
spellingShingle Athanasios Vassilopoulos
Athanasios Vassilopoulos
Fadi Shehadeh
Fadi Shehadeh
Fadi Shehadeh
Gregorio Benitez
Gregorio Benitez
Markos Kalligeros
Markos Kalligeros
Joanne S. Cunha
Cheston B. Cunha
Cheston B. Cunha
Eleftherios Mylonakis
Eleftherios Mylonakis
The incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents: A systematic review and meta-analysis
Frontiers in Pharmacology
psoriatic arthritis
opportunistic infections
BDMARDs
tsDMARDs
JAK inhibitors
herpes zoster
title The incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents: A systematic review and meta-analysis
title_full The incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents: A systematic review and meta-analysis
title_fullStr The incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents: A systematic review and meta-analysis
title_full_unstemmed The incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents: A systematic review and meta-analysis
title_short The incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents: A systematic review and meta-analysis
title_sort incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents a systematic review and meta analysis
topic psoriatic arthritis
opportunistic infections
BDMARDs
tsDMARDs
JAK inhibitors
herpes zoster
url https://www.frontiersin.org/articles/10.3389/fphar.2022.992713/full
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