Combined corticosteroid and cyclophosphamide therapy does not alter survival in idiopathic pulmonary fibrosis.

STUDY OBJECTIVES Treatment of patients with idiopathic pulmonary fibrosis (IPF) conventionally includes corticosteroids and cytotoxic agents. No study to date has adequately evaluated the benefits of this approach. This study retrospectively compared combination corticosteroid and cyclophosphamide therapy in a large population of patients who meet the current consensus definition of IPF. DESIGN Patients were identified retrospectively and treatment addressed on an intention-to-treat basis. Treated and untreated patients were matched by age and percentage of predicted FVC (FVC%) at the time of the initial visit. SETTING Two academic tertiary referral centers. PATIENTS OR PARTICIPANTS The diagnosis of IPF was based on current consensus criteria. A total of 164 patients (82 treated and 82 untreated) were included. INTERVENTIONS Treatment consisted of combined corticosteroid and cyclophosphamide therapy using a standardized protocol. MEASUREMENTS AND RESULTS There was no difference in age, FVC%, gender, or smoking status between groups. No survival difference was found between patients who were treated (median survival, 1,431 days) or untreated (median survival, 1,665 days) [p = 0.58]. The lack of treatment effect persisted when only those patients with a diagnosis by surgical biopsy (n = 24) or FVC% >/= 60 (n = 107) were analyzed. CONCLUSIONS Our data suggest that combined corticosteroid and cyclophosphamide therapy has no impact on survival in patients with IPF. This finding supports the evolving concept that chronic inflammation plays a minimal role in the progression of IPF and reinforces the importance of careful consideration of the risks and benefits of such therapies prior to their institution.

[1]  A. Nicholson,et al.  Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends. , 2003, American journal of respiratory and critical care medicine.

[2]  H. Collard,et al.  Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. , 2003, American journal of respiratory and critical care medicine.

[3]  F. Martinez,et al.  Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. , 2003, American journal of respiratory and critical care medicine.

[4]  F. Martinez,et al.  Radiological versus histological diagnosis in UIP and NSIP: survival implications , 2003, Thorax.

[5]  H. Collard,et al.  Demystifying idiopathic interstitial pneumonia. , 2003, Archives of internal medicine.

[6]  Rakesh K. Kumar.  Idiopathic pulmonary fibrosis: an epithelial/fibroblastic cross-talk disorder , 2002, Respiratory Research.

[7]  A. Katzenstein,et al.  Usual Interstitial Pneumonia: Histologic Study of Biopsy and Explant Specimens , 2002, The American journal of surgical pathology.

[8]  M. Selman,et al.  Molecular mechanisms of pulmonary fibrosis. , 2002, Frontiers in bioscience : a journal and virtual library.

[9]  R. Steele,et al.  Survival of patients with biopsy-proven usual interstitial pneumonia and nonspecific interstitial pneumonia , 2002, European Respiratory Journal.

[10]  Paul J. Friedman,et al.  American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors , 2002, American journal of respiratory and critical care medicine.

[11]  M. Selman,et al.  Idiopathic pulmonary fibrosis: an epithelial/fibroblastic cross-talk disorder , 2001, Respiratory research.

[12]  R. Strawderman,et al.  Histopathologic variability in usual and nonspecific interstitial pneumonias. , 2001, American journal of respiratory and critical care medicine.

[13]  D. Lynch,et al.  Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis. , 2001, American journal of respiratory and critical care medicine.

[14]  R. Strawderman,et al.  Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse reactions, response to therapy, and survival. , 2001, The American journal of medicine.

[15]  A. Pardo,et al.  Idiopathic Pulmonary Fibrosis: Prevailing and Evolving Hypotheses about Its Pathogenesis and Implications for Therapy , 2001, Annals of Internal Medicine.

[16]  A. Nicholson,et al.  The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis. , 2000, American journal of respiratory and critical care medicine.

[17]  D. Schroeder,et al.  Idiopathic pulmonary fibrosis: Impact of oxygen and colchicine, prednisone, or no therapy on survival. , 2000, American journal of respiratory and critical care medicine.

[18]  David A. Lynch,et al.  Idiopathic pulmonary fibrosis: Diagnosis and treatment: International Consensus Statement , 2000 .

[19]  G. Raghu,et al.  The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease: A prospective study. , 1999, Chest.

[20]  V. Petkov,et al.  A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. , 1999, The New England journal of medicine.

[21]  A. Nicholson,et al.  A histologic pattern of nonspecific interstitial pneumonia is associated with a better prognosis than usual interstitial pneumonia in patients with cryptogenic fibrosing alveolitis. , 1999, American journal of respiratory and critical care medicine.

[22]  G. Raghu,et al.  Treatment of Idiopathic Pulmonary Fibrosis with a New Antifibrotic Agent , Pirfenidone Results of a Prospective , Open-label Phase II Study , 1999 .

[23]  S. Swensen,et al.  Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosis. A randomized prospective study. Members of the Lung Study Group. , 1998, American journal of respiratory and critical care medicine.

[24]  J. Samet,et al.  Idiopathic pulmonary fibrosis: survival in population based and hospital based cohorts , 1998, Thorax.

[25]  J. Myers,et al.  Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. , 1998, American journal of respiratory and critical care medicine.

[26]  R. Hubbard,et al.  Survival in patients with cryptogenic fibrosing alveolitis: a population-based cohort study. , 1998, Chest.

[27]  K P Offord,et al.  Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. , 1998, American journal of respiratory and critical care medicine.

[28]  R. Wu,et al.  Changes in pulmonary function test results after 1 year of therapy as predictors of survival in patients with idiopathic pulmonary fibrosis. , 1995, Chest.

[29]  D. Schwartz,et al.  Determinants of survival in idiopathic pulmonary fibrosis. , 1994, American journal of respiratory and critical care medicine.

[30]  G. Raghu,et al.  Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial. , 1991, The American review of respiratory disease.

[31]  J. Darbyshire,et al.  Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis. , 1989, Thorax.

[32]  B. Burrows,et al.  Cryptogenic fibrosing alveolitis: response to corticosteroid treatment and its effect on survival , 1980, Thorax.

[33]  J. Meier-Sydow,et al.  [Long-term follow-up of lung function parameters in patients with idiopathic pulmonary fibrosis treated with prednisone and azathioprin or d-penicillamine (author's transl)]. , 1979, Praxis und Klinik der Pneumologie.

[34]  B. Heard,et al.  Prognosis of cryptogenic fibrosing alveolitis. , 1978, British medical journal.