Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial

King, Talmadge E.; Albera, Carlo; Bradford, Williamson Z.; Costabel, Ulrich; Hormel, Phil; Lancaster, Lisa; Noble, Paul W.; Sahn, Steven A.; Szwarcberg, Javier; Thomeer, Michiel; Valeyre, Dominique; Bois, Roland M. du

doi:10.1016/s0140-6736(09)60551-1

Cited by 489 publications

(338 citation statements)

References 19 publications

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“…However, in clinical studies, IFN-g treatment for idiopathic pulmonary fibrosis and liver fibrosis remained ineffective (17). The main reasons for the lack of beneficial clinical effects are the poor pharmacokinetics of IFN-g and severe side effects due to ubiquitous expression of the IFN-g receptor.…”

Section: Discussionmentioning

confidence: 99%

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Selective delivery of IFN‐γ to renal interstitial myofibroblasts: a novel strategy for the treatment of renal fibrosis

et al. 2014

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Renal fibrosis leads to end-stage renal disease demanding renal replacement therapy because no adequate treatment exists. IFN-g is an antifibrotic cytokine that may attenuate renal fibrosis. Systemically administered IFN-g causes side effects that may be prevented by specific drug targeting. Interstitial myofibroblasts are the effector cells in renal fibrogenesis. Here, we tested the hypothesis that cell-specific delivery of IFN-g to plateletderived growth factor receptor b (PDGFRb)-expressing myofibroblasts attenuates fibrosis in an obstructive nephropathy [unilateral ureteral obstruction (UUO)] mouse model. PEGylated IFN-g conjugated to PDGFRbrecognizing peptide [(PPB)-polyethylene glycol (PEG)-IFN-g] was tested in vitro and in vivo for antifibrotic properties and compared with free IFN-g. PDGFRb expression was >3-fold increased (P < 0.05) in mouse fibrotic UUO kidneys and colocalized with a-smooth muscle actin-positive (SMA + ) myofibroblasts.

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Section: Discussionmentioning

confidence: 99%

“…Recent studies suggested that IFN-g could be a useful therapeutic target to halt and prevent the development of fibrosis (16)(17)(18). IFN-g is a pleiotropic cytokine produced by various activated immune cells including NK cells and T cells.…”

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confidence: 99%

Selective delivery of IFN‐γ to renal interstitial myofibroblasts: a novel strategy for the treatment of renal fibrosis

et al. 2014

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“…The IFIGENIA trial was a multicentre, double-blind, randomised, placebo-controlled phase III trial which evaluated the effect of a high dose of oral NAC (i.e. 600 mg three times daily) together with low dose of Pirfenidone Antifibrotic CAPACITY 1 [23] Pirfenidone Antifibrotic CAPACITY 2 [23] Pirfenidone Antifibrotic ACE-IPF [24] Warfarin Anticoagulant TOMORROW [25] BIBF 1120 Tyrosine-kinase inhibitor DANIELS [26] Imatinib mesylate Tyrosine-kinase inhibitor STEP-IPF [27] Sildenafil Phosphodiesterase-5 inhibitor BUILD-1 [28] Bosentan Endothelin-receptor antagonist BUILD-3 [29] Bosentan Endothelin-receptor antagonist ARTEMIS-IPF [30] Ambrisentan Endothelin-receptor antagonist MUSIC-IPF [31] Macitentan Endothelin-receptor antagonist RAGHU [32] IFN-c Immunomodulation INSPIRE [33] IFN-c prednisone and azathioprine compared with prednisone and azathioprine alone [20]. The primary endpoint was the change in vital capacity (VC) and diffusing capacity of the lung for carbon monoxide (DLCO) at 12 months.…”

Section: Completed Clinical Trialsmentioning

confidence: 99%

“…RAGHU et al [32] tested the use of subcutaneous IFN-c for 58 weeks in 330 patients with IPF compared with placebo, without showing any effect in terms of progression-free survival, pulmonary function or quality of life. Subsequently a larger trial (INSPIRE) involving 800 IPF patients also failed to show any benefit in terms of mortality in favour of IFN-c [33].…”

Section: Interferon-cmentioning

confidence: 99%

Pharmacological treatment of idiopathic pulmonary fibrosis: from the past to the future

2013

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During the past decade important progress has been made regarding the pathogenesis of idiopathic pulmonary fibrosis (IPF), which is the most devastating form of idiopathic interstitial pneumonia with a median survival of 3 years. The knowledge gained has been used to design multicentre, randomised, placebo-controlled trials in order to investigate agents with different mechanisms of action. Encouraging results have led to licensing of the first IPF-specific drug, pirfenidone. However, the road to successful treatment is still long. The main aim for the future should be the careful design of clinical trials, by choosing the most clinically meaningful end-point and keeping in mind that combination of various agents may be more effective. This approach has been used in the treatment of lung cancer with which IPF presents many similarities. @ERSpublications Progress toward the treatment of IPF and aims for future clinical trials

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“…In the past 20 yrs many clinical trials have been conducted to evaluate the efficacy and safety of different and innovative drugs in the treatment of IPF. Table 1 demonstrates the heterogeneity of primary end-points used in these trials [8,9,[11][12][13][14][15][16][17][18]. Studies have generally measured lung function as this is the most valid end-point.…”

Section: Primary End-pointsmentioning

confidence: 99%

Challenges in idiopathic pulmonary fibrosis trials: the point on end-points

Albera¹

2011

Eur Respir Rev

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Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias and is associated with both a variable clinical course and a poor prognosis. Investigators involved in clinical trials and clinicians reviewing the IPF literature are confronted with daunting challenges in selecting reliable outcome measures, interpreting the clinical and statistical importance of these findings, and applying this knowledge to the clinical care of their patients. In order to evaluate the efficacy of new treatment regimens, a number of studies have been performed, employing a range of clinical and surrogate end-points. In most studies, the primary end-point consists of a single outcome measure. A desirable single clinical end-point for IPF should be reliable, valid, responsive to changes in disease status, clinically meaningful, predictive of clinical outcome and responsive to treatment effect of a given intervention. Proper consideration and effective choice of outcome measures used in IPF studies will help establish effective and achievable drug development programmes and will enable clinicians and investigators to make informed critical decisions in recommending a treatment regimen to their IPF patients.

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Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial

Cited by 489 publications

References 19 publications

Selective delivery of IFN‐γ to renal interstitial myofibroblasts: a novel strategy for the treatment of renal fibrosis

Selective delivery of IFN‐γ to renal interstitial myofibroblasts: a novel strategy for the treatment of renal fibrosis

Pharmacological treatment of idiopathic pulmonary fibrosis: from the past to the future

Challenges in idiopathic pulmonary fibrosis trials: the point on end-points

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