Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease

Justin Oldham, Cathryn Lee, Eleanor Valenzi, Leah J. Witt, Ayodeji Adegunsoye, Scully Hsu, Lena Chen, Steven Montner, Jonathan H. Chung, Imre Noth, Rekha Vij, Mary E. Strek

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Original languageEnglish (US)
Pages (from-to)117-122
Number of pages6
JournalRespiratory Medicine
Volume121
DOIs
StatePublished - Dec 1 2016

Fingerprint

Connective Tissue Diseases
Interstitial Lung Diseases
Azathioprine
Incidence
Idiopathic Pulmonary Fibrosis
Lung
Linear Models
Hospitalization
Mycophenolic Acid
Respiratory Rate
Cohort Studies
Therapeutics
Transplants

Keywords

  • Connective tissue disease
  • Idiopathic pulmonary fibrosis
  • Interstitial lung disease
  • Mycophenolate mofetil
  • Rheumatology
  • Usual interstitial pneumonia

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease. / Oldham, Justin; Lee, Cathryn; Valenzi, Eleanor; Witt, Leah J.; Adegunsoye, Ayodeji; Hsu, Scully; Chen, Lena; Montner, Steven; Chung, Jonathan H.; Noth, Imre; Vij, Rekha; Strek, Mary E.

In: Respiratory Medicine, Vol. 121, 01.12.2016, p. 117-122.

Research output: Contribution to journalArticle

Oldham, J, Lee, C, Valenzi, E, Witt, LJ, Adegunsoye, A, Hsu, S, Chen, L, Montner, S, Chung, JH, Noth, I, Vij, R & Strek, ME 2016, 'Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease', Respiratory Medicine, vol. 121, pp. 117-122. https://doi.org/10.1016/j.rmed.2016.11.007
Oldham, Justin ; Lee, Cathryn ; Valenzi, Eleanor ; Witt, Leah J. ; Adegunsoye, Ayodeji ; Hsu, Scully ; Chen, Lena ; Montner, Steven ; Chung, Jonathan H. ; Noth, Imre ; Vij, Rekha ; Strek, Mary E. / Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease. In: Respiratory Medicine. 2016 ; Vol. 121. pp. 117-122.
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abstract = "Background 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. Methods 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. Results 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. Conclusions 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.",
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AU - Oldham, Justin

AU - Lee, Cathryn

AU - Valenzi, Eleanor

AU - Witt, Leah J.

AU - Adegunsoye, Ayodeji

AU - Hsu, Scully

AU - Chen, Lena

AU - Montner, Steven

AU - Chung, Jonathan H.

AU - Noth, Imre

AU - Vij, Rekha

AU - Strek, Mary E.

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N2 - Background 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. Methods 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. Results 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. Conclusions 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.

AB - Background 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. Methods 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. Results 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. Conclusions 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.

KW - Connective tissue disease

KW - Idiopathic pulmonary fibrosis

KW - Interstitial lung disease

KW - Mycophenolate mofetil

KW - Rheumatology

KW - Usual interstitial pneumonia

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