title: Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease.
abstract: Azathioprine is a commonly prescribed therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). Combination therapy that included azathioprine was recently shown to increase the risk of death and hospitalization in patients with idiopathic pulmonary fibrosis. Whether azathioprine increases the risk of adverse outcomes in patients with fibrotic CTD-ILD, including those with CTD-associated usual interstitial pneumonia (UIP), remains unknown.
  
  
  
  A retrospective cohort analysis was performed to determine the combined incidence rate of death, transplant and respiratory hospitalization associated with azathioprine exposure. A fibrotic CTD-ILD cohort treated with mycophenolate mofetil served as a comparator group. Incidence rates were compared with an incidence rate ratio (IRR) generated by negative binomial regression. Longitudinal pulmonary function response was then assessed using mixed effects linear regression models.
  
  
  
  Fifty-four patients were treated with azathioprine and forty-three with mycophenolate. Medication discontinuation due to non-respiratory side effects occurred in 27% and 5% of the azathioprine and mycophenolate cohorts, respectively. The combined incidence rate of adverse outcomes was 0.015 and 0.013 for azathioprine and mycophenolate, respectively (IRR 1.23; 95% CI 0.49-3.12; p = 0.66). Similar incidence rates were observed among those with CTD-UIP (IRR 0.83; 95% CI 0.21-3.31; p = 0.79). Both groups demonstrated pulmonary function stability over time, with the azathioprine group demonstrating a marginal improvement.
  
  
  
  A significant minority of patients could not tolerate azathioprine due to non-respiratory side effects. Of those who did tolerate azathioprine, a similar incidence of adverse outcomes was observed as those treated with mycophenolate. Both therapies were associated with stability in pulmonary function.
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, The University of California at Davis, United States. Electronic address: joldham@ucdavis.edu.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Oldham
authors.affiliation: Department of Medicine, The University of Chicago, United States.
authors.forename: Cathryn
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, The University of Pittsburgh, United States.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Valenzi
authors.affiliation: Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, United States.
authors.forename: Leah J
authors.initials: LJ
authors.lastname: Witt
authors.affiliation: Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, United States.
authors.forename: Ayodeji
authors.initials: A
authors.lastname: Adegunsoye
authors.affiliation: Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, United States.
authors.forename: Scully
authors.initials: S
authors.lastname: Hsu
authors.affiliation: Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, United States.
authors.forename: Lena
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Radiology, The University of Chicago, United States.
authors.forename: Steven
authors.initials: S
authors.lastname: Montner
authors.affiliation: Department of Radiology, The University of Chicago, United States.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Chung
authors.affiliation: Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, United States.
authors.forename: Imre
authors.initials: I
authors.lastname: Noth
authors.affiliation: Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, United States.
authors.forename: Rekha
authors.initials: R
authors.lastname: Vij
authors.affiliation: Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, United States.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Strek
mesh_terms: D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D003240:Connective Tissue Diseases / Q000150:complications* / Q000503:physiopathology; D018592:Cross-Over Studies; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000627:therapeutic use; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D012042:Registries; D012189:Retrospective Studies; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine
keywords: Connective tissue disease; Idiopathic pulmonary fibrosis; Interstitial lung disease; Mycophenolate mofetil; Rheumatology; Usual interstitial pneumonia