title: Methotrexate use and risk of lung disease in psoriasis, psoriatic arthritis, and inflammatory bowel disease: systematic literature review and meta-analysis of randomised controlled trials.
abstract: OBJECTIVE
  To evaluate the relative risk of pulmonary disease among patients with psoriasis, psoriatic arthritis, and inflammatory bowel disease treated with methotrexate.
  
  
  METHODS
  PubMed, Cochrane central register of controlled trials, and Embase to 9 January 2014.
  
  
  METHODS
  Double blind randomised controlled trials of methotrexate versus placebo or active comparator agents in adults with psoriatic arthritis, psoriasis, or inflammatory bowel disease. Studies with fewer than 50 participants or of less than 12 weeks' duration were excluded.
  
  
  RESULTS
  Two investigators independently searched both databases. All authors reviewed selected studies. We compared relative risk differences using the Mantel-Haenszel random effects method to assess total respiratory adverse events, infectious respiratory adverse events, non-infectious respiratory adverse events, interstitial lung disease, and death.
  
  
  RESULTS
  Seven studies met our inclusion criteria, six with placebo as the comparator. Heterogeneity across the studies was not significant (I(2)=0%), allowing combination of trial results. 504 respiratory adverse events were documented in 1630 participants. Methotrexate was not associated with an increased risk of adverse respiratory events (relative risk 1.03, 95% confidence interval 0.90 to 1.17), respiratory infections (1.02, 0.88 to 1.19), or non-infectious respiratory events (1.07, 0.58 to 1.96). No pulmonary deaths occurred.
  
  
  CONCLUSIONS
  Findings suggested that there was no increased risk of lung disease in methotrexate treated patients with non-malignant inflammatory diseases. Given the limitations of the study, however, we cannot exclude a small but clinically important risk.
authors.affiliation: Department of Rheumatology, Galway University Hospitals, Galway, Republic of Ireland National University of Ireland Galway, Galway, Republic of Ireland drrichardconway@gmail.com.
authors.forename: Richard
authors.initials: R
authors.lastname: Conway
authors.affiliation: Department of Rheumatology, Connolly Hospital Blanchardstown, Dublin, Republic of Ireland.
authors.forename: Candice
authors.initials: C
authors.lastname: Low
authors.affiliation: Department of Rheumatology, Galway University Hospitals, Galway, Republic of Ireland.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Coughlan
authors.affiliation: National University of Ireland Galway, Galway, Republic of Ireland.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: O'Donnell
authors.affiliation: Department of Rheumatology, Galway University Hospitals, Galway, Republic of Ireland National University of Ireland Galway, Galway, Republic of Ireland.
authors.forename: John J
authors.initials: JJ
authors.lastname: Carey
mesh_terms: D000328:Adult; D015535:Arthritis, Psoriatic / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008171:Lung Diseases / Q000139:chemically induced*; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D011565:Psoriasis / Q000188:drug therapy*; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents; D008727:Methotrexate