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Clinical trials of investigational agents for IPF: a review of a Cochrane report.

Richeldi L - Respir. Res. (2013)

Bottom Line: In 2003, a review of data from studies of corticosteroid use in IPF patients found no evidence of a treatment effect.Similarly, very little evidence was found to support the use of immunomodulatory agents.A recent update of these Cochrane reviews failed to identify any new evidence supporting the use of corticosteroids in IPF.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Rare Lung Disease, University of Modena and Reggio Emilia, Modena, Italy. luca.richeldi@unimore.it

ABSTRACT
The magnitude of treatment effect can be assessed by a number of methods. One reliable method of collectively analysing data from randomised clinical trials is that used in Cochrane reviews. These systematic reviews identify and analyse the available evidence using the reliable method of meta-analysis. These often combine data from studies to provide robust evaluations of overall treatment effects. In 2003, a review of data from studies of corticosteroid use in IPF patients found no evidence of a treatment effect. Similarly, very little evidence was found to support the use of immunomodulatory agents. A recent update of these Cochrane reviews failed to identify any new evidence supporting the use of corticosteroids in IPF. However, a review of non-steroid agents for the treatment of IPF identified data from 15 RCTs that was suitable for analysis. Two trials of interferon gamma-1b were pooled and analysed, but no treatment effect was observed in terms of survival. Meta-analysis of three Phase III studies of pirfenidone treatment in IPF patients suggested that progression-free survival was significantly increased by 30%, demonstrating a reduction in the decline of lung function in IPF patients. In addition, there are numerous ongoing trials investigating potential therapeutic agents which provides hope for IPF patients and their doctors.

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Meta-analysis of progression-free survival with pirfenidone in IPF (Adapted from: 1. Spagnolo P, Del Giovane C, Luppi F, et al. Cochrane Database Syst Rev 2010, 9:CD003134. 2. Noble PW, Albera C, Bradford WZ, et al. Lancet 2011, 377:1760-1769. 3. Taniguchi H, Ebina M, Kondoh Y, et al. Eur Respir J 2010, 35:821-829.)
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Figure 1: Meta-analysis of progression-free survival with pirfenidone in IPF (Adapted from: 1. Spagnolo P, Del Giovane C, Luppi F, et al. Cochrane Database Syst Rev 2010, 9:CD003134. 2. Noble PW, Albera C, Bradford WZ, et al. Lancet 2011, 377:1760-1769. 3. Taniguchi H, Ebina M, Kondoh Y, et al. Eur Respir J 2010, 35:821-829.)

Mentions: For the treatment effect of pirfenidone, the three clinical trials that were eligible for analysis, i.e. the two large, international, randomized CAPACITY (004 and 006) trials [16] and the Japanese SP3 trial,[17] did not have a common primary endpoint (FVC and VC, respectively). However, the identification of data for inclusion in a specific Cochrane meta-analysis is based on pre-defined criteria. Progression-free survival (PFS) data, defined as either death or 10% decrease in FVC, was used as a secondary endpoint in the CAPACITY studies and the Japanese study published by Taniguchi et al.[17] Definitive evidence of clinical efficacy in a Phase 3 trial is best shown by a beneficial impact on a clinically meaningful endpoint—that is, an endpoint that directly measures how a patient feels (symptoms), functions (the ability to perform activities in daily life), or survives. For patients with IPF, there are currently no validated surrogate endpoints [18]. Nevertheless, PFS data from these studies were considered suitable for a meta-analysis based on these criteria. The overall result of this meta-analysis showed that treatment with pirfenidone reduced the risk of disease progression by 30% (HR 0.70, 95% CI 0.56 to 0.88; Figure 1) [13]. This highlights that pirfenidone is the only drug to date that has shown a significant effect on progression free survival, defined as either death or 10% FVC decrease, compared with placebo in patients with IPF.


Clinical trials of investigational agents for IPF: a review of a Cochrane report.

Richeldi L - Respir. Res. (2013)

Meta-analysis of progression-free survival with pirfenidone in IPF (Adapted from: 1. Spagnolo P, Del Giovane C, Luppi F, et al. Cochrane Database Syst Rev 2010, 9:CD003134. 2. Noble PW, Albera C, Bradford WZ, et al. Lancet 2011, 377:1760-1769. 3. Taniguchi H, Ebina M, Kondoh Y, et al. Eur Respir J 2010, 35:821-829.)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643529&req=5

Figure 1: Meta-analysis of progression-free survival with pirfenidone in IPF (Adapted from: 1. Spagnolo P, Del Giovane C, Luppi F, et al. Cochrane Database Syst Rev 2010, 9:CD003134. 2. Noble PW, Albera C, Bradford WZ, et al. Lancet 2011, 377:1760-1769. 3. Taniguchi H, Ebina M, Kondoh Y, et al. Eur Respir J 2010, 35:821-829.)
Mentions: For the treatment effect of pirfenidone, the three clinical trials that were eligible for analysis, i.e. the two large, international, randomized CAPACITY (004 and 006) trials [16] and the Japanese SP3 trial,[17] did not have a common primary endpoint (FVC and VC, respectively). However, the identification of data for inclusion in a specific Cochrane meta-analysis is based on pre-defined criteria. Progression-free survival (PFS) data, defined as either death or 10% decrease in FVC, was used as a secondary endpoint in the CAPACITY studies and the Japanese study published by Taniguchi et al.[17] Definitive evidence of clinical efficacy in a Phase 3 trial is best shown by a beneficial impact on a clinically meaningful endpoint—that is, an endpoint that directly measures how a patient feels (symptoms), functions (the ability to perform activities in daily life), or survives. For patients with IPF, there are currently no validated surrogate endpoints [18]. Nevertheless, PFS data from these studies were considered suitable for a meta-analysis based on these criteria. The overall result of this meta-analysis showed that treatment with pirfenidone reduced the risk of disease progression by 30% (HR 0.70, 95% CI 0.56 to 0.88; Figure 1) [13]. This highlights that pirfenidone is the only drug to date that has shown a significant effect on progression free survival, defined as either death or 10% FVC decrease, compared with placebo in patients with IPF.

Bottom Line: In 2003, a review of data from studies of corticosteroid use in IPF patients found no evidence of a treatment effect.Similarly, very little evidence was found to support the use of immunomodulatory agents.A recent update of these Cochrane reviews failed to identify any new evidence supporting the use of corticosteroids in IPF.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Rare Lung Disease, University of Modena and Reggio Emilia, Modena, Italy. luca.richeldi@unimore.it

ABSTRACT
The magnitude of treatment effect can be assessed by a number of methods. One reliable method of collectively analysing data from randomised clinical trials is that used in Cochrane reviews. These systematic reviews identify and analyse the available evidence using the reliable method of meta-analysis. These often combine data from studies to provide robust evaluations of overall treatment effects. In 2003, a review of data from studies of corticosteroid use in IPF patients found no evidence of a treatment effect. Similarly, very little evidence was found to support the use of immunomodulatory agents. A recent update of these Cochrane reviews failed to identify any new evidence supporting the use of corticosteroids in IPF. However, a review of non-steroid agents for the treatment of IPF identified data from 15 RCTs that was suitable for analysis. Two trials of interferon gamma-1b were pooled and analysed, but no treatment effect was observed in terms of survival. Meta-analysis of three Phase III studies of pirfenidone treatment in IPF patients suggested that progression-free survival was significantly increased by 30%, demonstrating a reduction in the decline of lung function in IPF patients. In addition, there are numerous ongoing trials investigating potential therapeutic agents which provides hope for IPF patients and their doctors.

Show MeSH