Idiopathic pulmonary fibrosis is a
chronic, progressive, and ultimately
fatal lung disease. After more than
a decade of clinical trials yielding
negative or inconsistent results,
two compounds, pirfenidone
and nintedanib, have finally been
proven to be effective in slowing
functional decline in idiopathic
pulmonary fibrosis and both have
now been approved in the USA,
Europe, and Japan.
Furthermore, the previously widely used combination of prednisone, azathioprine, and N-acetylcysteine has been shown to be harmful compared with placebo for patients with the disease. Accordingly, an update of the 2011 American Thoracic Society–European Respiratory Society– Japanese Respiratory Society–Latin American Thoracic Association clinical practice guideline on idiopathic pulmonary fibrosis treatment has been published this year. In keeping with the 2011 document, for the 2015 update, all available evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method and discussed at a multidisciplinary level. Recommendations were formulated and graded exclusively by group members with no financial or intellectual conflicts of interest. By contrast with the 2011 guidelines, the committee also included a patient representative. According to the GRADE system, recommendations are presented as either “strong” or “conditional” (the 2011 guidelines used the term “weak” rather than “conditional”). For a treatment with a conditional recommendation, it is judged that “the majority of individuals in this situation would want the suggested course of action but many would not”. The table shows a comparison of the 2011 and 2015 recommendations. The major change in the 2015 recommendations is the introduction of a conditional recommendation for the use of pirfenidone (which received a weak recommendation against its use in 2011), and of nintedanib, a multitarget tyrosine kinase inhibitor that was not included in the previous guideline. Because of the absence of a head-to-head comparison, the guideline does not provide recommendations for one treatment regimen over the other. The three-drug regimen, prednisone–azathioprine– N-acetylcysteine, received a strong recommendation against its use, whereas recommendations for N-acetylcysteine monotherapy (conditional recommendation against use) and for anti-acid treatment (conditional recommendation for use) remain unchanged. The new guideline document represents the recent substantial advances in the pharmacological treatment of idiopathic pulmonary fi brosis. A weakness of the document is the fact that decisions were made within a month of publication of key phase 3 trial data and before information provided as part of regulatory submissions had become available (data that have had important consequences in changing the US Food and Drug Administration’s opinion of forced vital capacity [FVC] as a clinically relevant effi cacy measure in idiopathic pulmonary fibrosis).
Furthermore, the guideline committee factored drug cost into their decisionmaking process without doing a detailed health economic analysis This approach has resulted in the apparent incongruity of drugs, with high-quality clinical trial data being given the same conditional level of recommendation as anti-acid therapy (which has never been tested in a randomised controlled trial).4 Importantly, the guidelines emphasise several major issues that need further research: first, existing anti-fibrotic therapy slows disease decline, but neither halts nor cures idiopathic pulmonary fibrosis, and thus the need for new pharmacotherapies persists; second, the effectiveness of anti-fibrotic therapy beyond the 52–72-week duration of clinical trials remains to be fully defined; third, whether or not treatment is benefi cial in more advanced disease (eg, FVC <50%) is unknown; and fourth, combination anti-fibrotic therapy might provide synergistic eff ects with larger functional benefit, although trial data showing both safety and efficacy are needed before such an approach can be considered. In summary, the updated guidelines represent the important developments that have occurred in the pharmacological treatment of idiopathic pulmonary fibrosis, while simultaneously drawing attention to the continued large unmet clinical need of individuals afflicted by this terrible disease.This approach has resulted in the apparent incongruity of drugs, with high-quality clinical trial data being given the same conditional level of recommendation as anti-acid therapy (which has never been tested in a randomised controlled trial). Importantly, the guidelines emphasise several major issues that need further research: first, existing anti-fibrotic therapy slows disease decline, but neither halts nor cures idiopathic pulmonary fibrosis, and thus the need for new pharmacotherapies persists; second, the effectiveness of anti-fibrotic therapy beyond the 52–72-week duration of clinical trials remains to be fully defined; third, whether or not treatment is benefi cial in more advanced disease (eg, FVC <50%) is unknown; and fourth, combination anti-fibrotic therapy might provide synergistic eff ects with larger functional benefit,6 although trial data showing both safety and efficacy are needed before such an approach can be considered. In summary, the updated guidelines represent the important developments that have occurred in the pharmacological treatment of idiopathic pulmonary fibrosis, while simultaneously drawing attention to the continued large unmet clinical need of individuals afflicted by this terrible disease.
Reference: www.thelancet.com/respiratory Vol 3 September 2015
Download Full Article: http://www.mediafire.com/view/xxfxexs43hv479k/PIIS2213260015003227.pdf
Furthermore, the previously widely used combination of prednisone, azathioprine, and N-acetylcysteine has been shown to be harmful compared with placebo for patients with the disease. Accordingly, an update of the 2011 American Thoracic Society–European Respiratory Society– Japanese Respiratory Society–Latin American Thoracic Association clinical practice guideline on idiopathic pulmonary fibrosis treatment has been published this year. In keeping with the 2011 document, for the 2015 update, all available evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method and discussed at a multidisciplinary level. Recommendations were formulated and graded exclusively by group members with no financial or intellectual conflicts of interest. By contrast with the 2011 guidelines, the committee also included a patient representative. According to the GRADE system, recommendations are presented as either “strong” or “conditional” (the 2011 guidelines used the term “weak” rather than “conditional”). For a treatment with a conditional recommendation, it is judged that “the majority of individuals in this situation would want the suggested course of action but many would not”. The table shows a comparison of the 2011 and 2015 recommendations. The major change in the 2015 recommendations is the introduction of a conditional recommendation for the use of pirfenidone (which received a weak recommendation against its use in 2011), and of nintedanib, a multitarget tyrosine kinase inhibitor that was not included in the previous guideline. Because of the absence of a head-to-head comparison, the guideline does not provide recommendations for one treatment regimen over the other. The three-drug regimen, prednisone–azathioprine– N-acetylcysteine, received a strong recommendation against its use, whereas recommendations for N-acetylcysteine monotherapy (conditional recommendation against use) and for anti-acid treatment (conditional recommendation for use) remain unchanged. The new guideline document represents the recent substantial advances in the pharmacological treatment of idiopathic pulmonary fi brosis. A weakness of the document is the fact that decisions were made within a month of publication of key phase 3 trial data and before information provided as part of regulatory submissions had become available (data that have had important consequences in changing the US Food and Drug Administration’s opinion of forced vital capacity [FVC] as a clinically relevant effi cacy measure in idiopathic pulmonary fibrosis).
Furthermore, the guideline committee factored drug cost into their decisionmaking process without doing a detailed health economic analysis This approach has resulted in the apparent incongruity of drugs, with high-quality clinical trial data being given the same conditional level of recommendation as anti-acid therapy (which has never been tested in a randomised controlled trial).4 Importantly, the guidelines emphasise several major issues that need further research: first, existing anti-fibrotic therapy slows disease decline, but neither halts nor cures idiopathic pulmonary fibrosis, and thus the need for new pharmacotherapies persists; second, the effectiveness of anti-fibrotic therapy beyond the 52–72-week duration of clinical trials remains to be fully defined; third, whether or not treatment is benefi cial in more advanced disease (eg, FVC <50%) is unknown; and fourth, combination anti-fibrotic therapy might provide synergistic eff ects with larger functional benefit, although trial data showing both safety and efficacy are needed before such an approach can be considered. In summary, the updated guidelines represent the important developments that have occurred in the pharmacological treatment of idiopathic pulmonary fibrosis, while simultaneously drawing attention to the continued large unmet clinical need of individuals afflicted by this terrible disease.This approach has resulted in the apparent incongruity of drugs, with high-quality clinical trial data being given the same conditional level of recommendation as anti-acid therapy (which has never been tested in a randomised controlled trial). Importantly, the guidelines emphasise several major issues that need further research: first, existing anti-fibrotic therapy slows disease decline, but neither halts nor cures idiopathic pulmonary fibrosis, and thus the need for new pharmacotherapies persists; second, the effectiveness of anti-fibrotic therapy beyond the 52–72-week duration of clinical trials remains to be fully defined; third, whether or not treatment is benefi cial in more advanced disease (eg, FVC <50%) is unknown; and fourth, combination anti-fibrotic therapy might provide synergistic eff ects with larger functional benefit,6 although trial data showing both safety and efficacy are needed before such an approach can be considered. In summary, the updated guidelines represent the important developments that have occurred in the pharmacological treatment of idiopathic pulmonary fibrosis, while simultaneously drawing attention to the continued large unmet clinical need of individuals afflicted by this terrible disease.
Reference: www.thelancet.com/respiratory Vol 3 September 2015
Download Full Article: http://www.mediafire.com/view/xxfxexs43hv479k/PIIS2213260015003227.pdf
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