The aim is to evaluate the published evidence on whether methotrexate (MTX) use causes progressive fibrotic interstitial lung disease (fILD). This PRISMA-compliant systematic review has been registered electronically with PROSPERO 2018 ID CRD42018087838, Centre of review and dissemination at the University of York. A total of 29 articles met the inclusion criteria. Thirteen articles were found to support the claim that MTX causes fILD. They all had a low Downs and Black quality score (< 6/27). Their ‘risk of bias’ assessment scores indicated serious to critical risk of bias. The 16 articles rejecting the claim that MTX causes fILD were of higher quality as indicated by their Downs and Black score. Their ‘risk of bias’ assessment scores suggested only a low to moderate risk of bias. This systematic literature review supports the finding that MTX does not cause fILD in humans. Three studies suggest that MTX treatment may actually improve outcomes in patients with rheumatoid arthritis (RA) associated fILD by slowing down ILD progression.

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