The effect of smoking on response to methotrexate in rheumatoid arthritis patients: A systematic review and meta-analysis

Abstract

ABSTRACT Objectives In the current study, we aimed to investigate the effect of smoking on inadequate response to methotrexate (MTX-IR) in rheumatoid arthritis (RA) patients. Methods We searched PubMed, Embase, and Web of Science until 6 June 2022. Observational or interventional studies investigating MTX-IR in RA patients based on smoking status were included. Two independent reviewers assessed the risk of bias and the certainty of the evidence using the Risk of Bias in Nonrandomized Studies–of Interventions and Grades of Recommendation, Assessment, Development, and Evaluation tools, respectively. Results We included 23 studies in the systematic review and 13 in the meta-analysis. Of the 13 included studies, 6 had a moderate risk, 3 had a serious risk, and 4 had a critical risk of bias. The overall random-effect meta-analysis suggested that smokers were 58% more likely to be MTX-IR when compared with nonsmokers [odds ratio (OR) 1.58, 95% confidence interval 1.21–2.06; P = .001; I2 = 69.3%]. The common-effect meta-analysis of the adjusted ORs demonstrated an overall OR of 2.69 (1.88–3.83; P < .001; I2 = 27.1%). Conclusions The current study showed that smoking is a significant predictor of MTX-IR, especially in disease-modifying antirheumatic drug–naïve early RA patients, as most of the included studies in the meta-analysis consisted of this population.