P154 Systematic literature review investigating whether methotrexate causes chronic interstitial pulmonary fibrosis

Abstract

Background Methotrexate is a treatment widely used in many medical conditions. Methotrexate is associated with a potentially fatal methotrexate pneumonitis. The aim of this study is to undertake a systematic literature review to evaluate the published evidence on whether methotrexate causes a chronic interstitial pulmonary fibrosis in humans. Methods The PRISMA checklist for systematic reviews was followed. The review was registered with Prospero. Electronic searches were performed using scientific literature databases for articles relating to methotrexate use and interstitial pulmonary fibrosis. Non-English, non-human and all other methotrexate complications apart from interstitial lung fibrosis were excluded from this study. Data collected were subsequently separated into two groups (one supporting and one rejecting the claim of methotrexate-induced lung fibrosis). Articles in each group were analysed based on their level of evidence using Oxford (UK) and Downs and Black quality scoring. Risk of bias was assessed with (ROBINS-I) assessment tool. Results A total of 22 articles met the inclusion criteria, 11 articles were found to support the claim that methotrexate causes lung fibrosis and another 11 found otherwise. It was found that 63% of the articles from the supporting groups were published before the year 2000. All articles in the supporting papers contain a low level of Oxford graded evidence ( Level 2b) and 18/27 or more Downs and Black score. The rejecting group contains articles with a low and moderate risk of bias while the articles in the supporting group contain serious to critical level of bias. Conclusion Our systematic literature review found no high quality unbiased evidence that methotrexate causes chronic interstitial lung fibrosis in humans. The claim that methotrexate causes lung fibrosis seems to be derived from two case reports and ill-defined terminology used in early publications where chronic pulmonary fibrosis is considered synonymous with methotrexate pneumonitis. It is important to reject the hypothesis that methotrexate causes chronic pulmonary fibrosis across all disciplines as it is causing patients to have their methotrexate therapy withdrawn without any good clinical evidence.