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

Julio A. Huapaya, Leann Silhan, Iago Pinal-Fernandez, Maria Casal-Dominguez, Cheilonda Johnson, Jemima Albayda, Julie Paik, Abanti Sanyal, Andrew L. Mammen, Lisa Christopher-Stine, Sonye Danoff

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)896-906
Number of pages11
JournalCHEST
Volume156
Issue number5
DOIs
StatePublished - Nov 1 2019

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Mycophenolic Acid
Myositis
Interstitial Lung Diseases
Azathioprine
Prednisone
Therapeutics
Lung Volume Measurements
Connective Tissue Diseases
Carbon Monoxide
Retrospective Studies
Smoking
Steroids

Keywords

  • antisynthetase syndrome
  • azathioprine
  • interstitial lung disease
  • mycophenolate mofetil
  • myositis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Long-Term Treatment With Azathioprine and Mycophenolate Mofetil for Myositis-Related Interstitial Lung Disease. / Huapaya, Julio A.; Silhan, Leann; Pinal-Fernandez, Iago; Casal-Dominguez, Maria; Johnson, Cheilonda; Albayda, Jemima; Paik, Julie; Sanyal, Abanti; Mammen, Andrew L.; Christopher-Stine, Lisa; Danoff, Sonye.

In: CHEST, Vol. 156, No. 5, 01.11.2019, p. 896-906.

Research output: Contribution to journalArticle

Huapaya, Julio A. ; Silhan, Leann ; Pinal-Fernandez, Iago ; Casal-Dominguez, Maria ; Johnson, Cheilonda ; Albayda, Jemima ; Paik, Julie ; Sanyal, Abanti ; Mammen, Andrew L. ; Christopher-Stine, Lisa ; Danoff, Sonye. / Long-Term Treatment With Azathioprine and Mycophenolate Mofetil for Myositis-Related Interstitial Lung Disease. In: CHEST. 2019 ; Vol. 156, No. 5. pp. 896-906.
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abstract = "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.",
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T1 - Long-Term Treatment With Azathioprine and Mycophenolate Mofetil for Myositis-Related Interstitial Lung Disease

AU - Huapaya, Julio A.

AU - Silhan, Leann

AU - Pinal-Fernandez, Iago

AU - Casal-Dominguez, Maria

AU - Johnson, Cheilonda

AU - Albayda, Jemima

AU - Paik, Julie

AU - Sanyal, Abanti

AU - Mammen, Andrew L.

AU - Christopher-Stine, Lisa

AU - Danoff, Sonye

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

KW - antisynthetase syndrome

KW - azathioprine

KW - interstitial lung disease

KW - mycophenolate mofetil

KW - myositis

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