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Immunomodulatory agents for idiopathic pulmonary fibrosis

  • Review
  • Intervention




Idiopathic Pulmonary Fibrosis (IPF) or Usual Interstitial Pneumonia (UIP) is a form of chronic fibrosing interstitial pneumonia of unknown aetiology, with progressively deteriorating respiratory function and ultimately death from respiratory failure. Most treatments are intended to suppress inflammation but none has been proven to alter this process. The most widespread approach uses oral corticosteroids; others use immunosuppressive, immunomodulatory or anti-fibrotic agents, alone or with corticosteroids. A Cochrane review of corticosteroids in IPF has found no evidence that they are of benefit.


To determine the effect of non-corticosteroid immunosuppressive, anti-fibrotic and immunomodulatory agents in the treatment of IPF(UIP).

Search strategy

We searched the Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library, Issue 2 2003), MEDLINE (January 1966 to April 2003), EMBASE (January 1985 to April 2003) and with additional handsearching.

Selection criteria

RCTs/CCTs utilising non-corticosteroid immunosuppressive, anti-fibrotic or immunomodulatory agents versus either placebo or corticosteroids alone in adult patients with histological evidence of IPF(UIP) or with a diagnosis consistent with published American Thoracic Society guidelines were included.

Data collection and analysis

We retrieved abstracts of identified articles and reviewed those possibly fulfilling inclusion criteria and included or excluded. Two reviewers assessed the studies for inclusion in the review. Where doubt existed a third reviewer re-assessed the article and consensus was obtained. Methodological quality was assessed using the Jadad scale and the Cochrane assessment of allocation of concealment.

Main results

59 studies were identified. Quality was generally poor. Only three RCT/CCTs were suitable for meta-analysis, two lesser quality RCTs were included in discussion only, 52 studies were excluded and two ongoing trials were identified.

Each high quality trial used a different agent (azathioprine, colchicine, interferon-gamma 1b) and meaningful comparisons are not possible. Azathioprine and Interferon were studied as additional therapy, whilst colchicine was compared with oral corticosteroids. Only interferon was shown to produce any significant improvement in pulmonary function and arterial oxygenation. There may be a small (but undefined) long term survival advantage for azathioprine.

One of the lower quality studies showed a marginal benefit for cyclophosphamide and prednisone over prednisone alone; the other showed no benefit for azathioprine and prednisone over prednisone alone. There are no high quality studies utilising cyclophosphamide.

Authors' conclusions

There is little good quality information regarding the efficacy of non-corticosteroid agents in IPF(UIP). The older agents have generally not been well evaluated. A number of new agents require further evaluation. Currently there is little to justify the routine use of any non-corticosteroid agent in the management of IPF(UIP).

Plain language summary

Immunomodulatory agents for idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a form of progressive lung disease which ultimately leads to death. The cause is unknown, but the disease is characterised by scar tissue in the lungs. This prevents the lungs from working effectively. Standard treatment uses oral corticosteroids, but there remains some uncertainty as to whether this treatment is effective. Immunomodulatory agents such as azathioprine and cyclophosphamide have been used to treat the disease because it is thought they might prevent inflammation. The review found only three high quality trials of these drugs. The effects of both colchicine and azathioprine were disappointing when assessed by these good quality trials, failing to show any significant additional benefit over oral corticosteroids. Azathioprine may lead to a small long term survival benefit. The single study using interferon showed significant benefits, but the results require confirmation. There are no high quality studies for other agents. Currently there is no good evidence to support routine use of immunosuppressive, anti-fibrotic or immunomodulatory agents in the management of IPF. Interferon and other new drugs may be of benefit, but further studies are required.

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