Long-Term Treatment With Azathioprine and Mycophenolate Mofetil for Myositis-Related Interstitial Lung Disease

Chest. 2019 Nov;156(5):896-906. doi: 10.1016/j.chest.2019.05.023. Epub 2019 Jun 22.


Background: The efficacy of azathioprine (AZA) and mycophenolate mofetil (MMF) for interstitial lung disease (ILD) has been described, but mainly in connective tissue disease-associated ILD. The objective of this study was to evaluate the effect of AZA and MMF on lung function and prednisone dose in myositis-related ILD (M-ILD).

Methods: In this retrospective study, patients with M-ILD seen at Johns Hopkins and treated with AZA or MMF and no other steroid-sparing agents were included. Linear mixed-effects models adjusted for sex, age, antisynthetase antibody, and smoking status were used to compare the change in FVC % predicted, diffusing capacity of the lungs for carbon monoxide (Dlco) % predicted, and prednisone dose.

Results: Sixty-six patients with M-ILD were treated with AZA and 44 with MMF. At treatment initiation, mean FVC % predicted and Dlco % predicted were significantly lower in the AZA group than in the MMF group. In both groups, FVC % predicted improved and the prednisone dose was reduced over 2 to 5 years; however, for Dlco % predicted, only the AZA group improved. The adjusted model showed no significant difference in posttreatment FVC % predicted or Dlco % predicted between groups (mean difference of 1.9 and -8.2, respectively), but a 6.6-mg lower dose of prednisone at 36 months in the AZA group. Adverse events were more frequent with AZA than MMF (33.3% vs 13.6%; P = .04).

Conclusions: In M-ILD, AZA treatment was associated with improved FVC % predicted and Dlco % predicted, and lower prednisone dose. Patients treated with MMF had improved FVC % predicted and lower prednisone dose. After 36 months, patients treated with AZA received a lower prednisone dose than those treated with MMF.

Keywords: antisynthetase syndrome; azathioprine; interstitial lung disease; mycophenolate mofetil; myositis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azathioprine / therapeutic use*
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume / physiology*
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Lung / diagnostic imaging
  • Lung / physiopathology
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / etiology
  • Lung Diseases, Interstitial / physiopathology
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use*
  • Myositis / complications*
  • Myositis / drug therapy
  • Prednisone / therapeutic use
  • Respiratory Function Tests
  • Retrospective Studies
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome


  • Enzyme Inhibitors
  • Glucocorticoids
  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Azathioprine
  • Prednisone