Chest
Volume 125, Issue 6, June 2004, Pages 2169-2174
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Clinical Investigations
Inflammatory Lung Disease
Combined Corticosteroid and Cyclophosphamide Therapy Does Not Alter Survival in Idiopathic Pulmonary Fibrosis

https://doi.org/10.1378/chest.125.6.2169Get rights and content

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.

Section snippets

Study Population

Patients seen at two institutions (National Jewish Medical and Research Center, Denver, CO and the Mayo Clinic, Rochester, MN) between 1984 and 2002 who received a diagnosis of IPF were retrospectively reviewed. Treated patients (n = 543) and untreated patients (n = 155) were matched by age at diagnosis (within 5 years) and baseline FVC% (within 5%). This identified 164 patients (82 treated/untreated matched patient pairs) who comprised the study group. The diagnosis of IPF was made by surgical

Patient Characteristics

Treated and untreated patients were well matched for age at diagnosis, gender, baseline FVC%, and smoking history (Table 1). The overall mean age at diagnosis was 67.6 years. There were 127 men and 37 women, equally distributed between the two groups. Overall, baseline FVC% was 67.2. A history of current or former smoking was present in approximately 70% of patients. Surgical lung biopsy was obtained in all treated patients and in 12 of the untreated patients (15%).

Survival: Treated vs Untreated

There was no difference in

DISCUSSION

Combined treatment with corticosteroid and cyclophosphamide therapy does not appear to alter survival in patients with IPF. The lack of survival benefit persists when only surgical biopsy-proven cases or cases with a FVC% ≥ 60 are analyzed. These findings support the concept that chronic persistent inflammation plays little role in the progression of IPF.19, 20, 21

Interpretation of previous studies addressing the impact of corticosteroid and cytotoxic therapy on survival is difficult and

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      Citation Excerpt :

      La corticothérapie est associée à une morbidité importante à long terme [119]. Les biais méthodologiques [120–122] ou les résultats contradictoires [123,124] des études ayant évalué l’effet de la corticothérapie associée à un traitement immunomodulateur (par exemple, azathioprine ou cyclophosphamide) sur la survie des patients ne permettent pas de recommander cette association dans le traitement de la FPI. Une corticothérapie orale ne dépassant pas 10 mg/j de prednisone est parfois proposée pour son effet sur la toux lorsqu’elle est invalidante (cf. ci-dessous) [125].

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    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]).

    Supported by National Institutes of Health grants SCOR HL6767 and NHLBI HL07085.

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