Next Article in Journal
Effect of Sarcopenia on Sleep Disturbance in Patients with Chronic Liver Diseases
Previous Article in Journal
Effects of Corticosteroid Treatment and Antigen Avoidance in a Large Hypersensitivity Pneumonitis Cohort: A Single-Centre Cohort Study
Article Menu

Export Article

Open AccessArticle
J. Clin. Med. 2019, 8(1), 15;

Risk of Infection with Methotrexate Therapy in Inflammatory Diseases: A Systematic Review and Meta-Analysis

Department of Medicine, National University of Ireland Galway, Galway, Ireland
Department of Rheumatic Diseases, St. James’s University Hospital, Dublin, Ireland
Department of Rheumatic Diseases, Galway University Hospitals, Galway, Ireland
Author to whom correspondence should be addressed.
Received: 16 November 2018 / Revised: 12 December 2018 / Accepted: 15 December 2018 / Published: 21 December 2018
(This article belongs to the Section Pharmacology)
Full-Text   |   PDF [2976 KB, uploaded 4 January 2019]   |  


The aim of this study was to determine the risk of infection in adults with inflammatory rheumatic diseases (IRDs) treated with methotrexate. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing methotrexate versus placebo in adults using MEDLINE, EMBASE, and CENTRAL databases from 1980 to August 2017. The primary outcome was the risk of infection associated with methotrexate therapy. We chose a random effect model to summarize adverse event outcomes as risk ratios (RRs) and related 95% confidence intervals (95% CI). Twelve RCTs (total patients 1146) met the inclusion criteria for our main analysis, and ten for risk of serious infection (total patients 906). Overall, methotrexate was associated with increased risk of infection in rheumatoid arthritis (RA) (RR: 1.25; 95% CI, 1.01–1.56; p = 0.04; I2 = 0%), but not in other non-RA IRD populations. There was no increased risk of total infections (RR: 1.14; 95% CI, 0.98–1.34; p = 0.10; I2 = 0%) or serious infections (RR: 0.76; 95% CI, 0.11–5.15; p = 0.78; I2 = 0%) in all included IRDs. Conclusively, methotrexate use in IRDs is associated with a higher risk of all infections in RA, but not in other non-RA (IRD) populations. There is no increased risk of serious infections. View Full-Text
Keywords: methotrexate; infections and arthritis; inflammation; DMARDs methotrexate; infections and arthritis; inflammation; DMARDs

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Ibrahim, A.; Ahmed, M.; Conway, R.; Carey, J.J. Risk of Infection with Methotrexate Therapy in Inflammatory Diseases: A Systematic Review and Meta-Analysis. J. Clin. Med. 2019, 8, 15.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top