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Immunomodulatory agents for idiopathic pulmonary fibrosis

Immunomodulatory agents for idiopathic pulmonary fibrosis
Immunomodulatory agents for idiopathic pulmonary fibrosis
BACKGROUND:
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.

OBJECTIVES:
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.

REVIEWER'S 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).
1469-493X
1-56
Davies, H.R.
a2f3db9c-036d-4903-804c-e6f30b7a918d
Richeldi, L.
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26
Walters, E.H.
58b6aed5-e61f-40d7-b9d4-6b2da4a966cc
Davies, H.R.
a2f3db9c-036d-4903-804c-e6f30b7a918d
Richeldi, L.
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26
Walters, E.H.
58b6aed5-e61f-40d7-b9d4-6b2da4a966cc

Davies, H.R., Richeldi, L. and Walters, E.H. (2003) Immunomodulatory agents for idiopathic pulmonary fibrosis. Cochrane Database of Systematic Reviews, CD003134 (3), 1-56. (doi:10.1002/14651858.CD003134). (PMID:12917947)

Record type: Article

Abstract

BACKGROUND:
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.

OBJECTIVES:
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.

REVIEWER'S 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).

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More information

Published date: 22 April 2003
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 368943
URI: https://eprints.soton.ac.uk/id/eprint/368943
ISSN: 1469-493X
PURE UUID: 33e7837d-7b46-406b-bc91-eaf8841ffbae

Catalogue record

Date deposited: 03 Oct 2014 14:12
Last modified: 05 Oct 2018 12:09

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