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. 2018 Dec 21;8(1):15.
doi: 10.3390/jcm8010015.

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

Ammar Ibrahim  1 , Mohammed Ahmed  2 , Richard Conway  3 , John J Carey  4
Affiliations

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

Ammar Ibrahim et al. J Clin Med. .

Abstract

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.

Keywords: DMARDs; infections and arthritis; inflammation; methotrexate.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flow diagram: Risk of infection of methotrexate therapy in inflammatory diseases (abbreviations: MTX—Methotrexate, PBO—Placebo, RCT—Randomized Controlled trial, UVB: Ultra violet B).
Figure 2
Figure 2
Forest plot: Risk of infection of methotrexate therapy in inflammatory diseases (abbreviations: MTX—methotrexate, PBO—placebo) (Studies included: [27,28,29,30,31,33,34,35,36,37,38,39]).
Figure 3
Figure 3
Forest plot: risk of serious infection of MTX vs PBO in inflammatory diseases (Studies included: [28,30,32,33,34,35,36,37,38,39]).
Figure 4
Figure 4
Forest plot: Subgroup analyses in risk of infection with methotrexate therapy in inflammatory diseases (Studies included: [27,28,29,30,31,33,34,35,36,37,38,39]).
Figure 5
Figure 5
Forest plot: Risk of infection of methotrexate therapy in non-RA inflammatory diseases. (Studies included: [27,28,30,31,33,34,36,37,39]).
See this image and copyright information in PMC

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