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

Richard Conway,Ammar Ibrahim,Mohammed Ahmed,John J Carey

doi:10.3390/jcm8010015

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.

Highlights

Methotrexate is a commonly prescribed medication which primarily inhibits DNA synthesis [1,2].It is highly efficacious and is the anchor therapy in the management of rheumatoid arthritis (RA) and a primary therapeutic choice in many other inflammatory and rheumatic conditions [3,4,5,6,7].Serious side effects have been ascribed to methotrexate therapy including bone marrow suppression, pulmonary disease, liver fibrosis, and infection [8,9,10,11]
Screening of the titles and abstracts resulted in the further exclusion of 17,473 articles, leaving 299 articles deemed suitable for a secondary eligibility assessment through a secondary detailed review of the full-text articles
Based on our eligibility criteria, the inflammatory rheumatic conditions (IRDs) that were included in this review were rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic sclerosis, and Crohn’s disease

Summary

Introduction

Methotrexate is a commonly prescribed medication which primarily inhibits DNA synthesis [1,2].It is highly efficacious and is the anchor therapy in the management of rheumatoid arthritis (RA) and a primary therapeutic choice in many other inflammatory and rheumatic conditions [3,4,5,6,7].Serious side effects have been ascribed to methotrexate therapy including bone marrow suppression, pulmonary disease, liver fibrosis, and infection [8,9,10,11]. Methotrexate is a commonly prescribed medication which primarily inhibits DNA synthesis [1,2] It is highly efficacious and is the anchor therapy in the management of rheumatoid arthritis (RA) and a primary therapeutic choice in many other inflammatory and rheumatic conditions [3,4,5,6,7]. Studies report an association of infections with specific rheumatic conditions such as RA, or with immune-suppressant medications used to treat these conditions, which may lead to poorer outcomes or death [12,13,14,15]. This may be true for some therapies, biologic medications [16]. Infection is the third leading cause of death in RA populations [18]

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