Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a deadly disease with no effective treatment. The purpose of this randomised prospective multicentric study was to characterise the clinical effects of interferon gamma (IFN-c) 1b administered subcutaneously thrice weekly versus colchicine for 2 yrs. This study had no pre-specified end-points.Fifty consecutive IPF patients were randomised. Patients with mild-to-moderate IPF were eligible for the study if they had histologically proven IPF, or, in the absence of surgical biopsy, fulfilled the European Respiratory Society/American Thoracic Society criteria.In the intent-to-treat population, five out of 32 (15.6%) IFN-c-1b patients and seven out of 18 (38.8%) colchicine patients died after a median follow-up period of 25 months Patients treated with IFN-c 1b showed a better outcome after 2 yrs of therapy, and fewer symptoms, as assessed using the St George's Respiratory Questionnaire, after 12 months of therapy. Also, the IFN-c-1b group exhibited a higher forced vital capacity (percentage of the predicted value) after 24 months of treatment. No significant differences were detected in resting arterial oxygen tension, total lung capacity (% pred), transfer factor of the lung for carbon monoxide (% pred) and high-resolution computed tomographic scoring between the two treatment groups.These data suggest that long-term treatment with interferon gamma 1b may improve survival and outcome in patients with mild-to-moderate idiopathic pulmonary fibrosis. Further studies are needed to verify these results.

Review: New perspectives in the treatment of idiopathic pulmonary fibrosis

“…This study enrolled 50 consecutive patients with mild-to-moderate IPF, either with histologically-proven UIP or, in the absence of surgical biopsy, with a a clinical diagnosis of IPF according to the ATS/ERS criteria [ATS/ERS Consensus 2002]. In this study, mortality was lower in the IFN-γ arm and, in addition, IFN-γ treated patients showed fewer symptoms and had better pulmonary function after 24 months of treatment, again suggesting that treatment with IFN-γ might improve survival in patients with mild-to-moderate idiopathic pulmonary fibrosis [Antoniou et al 2006]. This latter concept was somewhat reinforced by the reports of cases of acute respiratory failure, leading to death or lung transplantation, in patients with advanced IPF treated with IFN-γ [Honoré et al 2003], which raised concerns that patients in more advanced IPF stages might be at increased risk of severe adverse reactions [Selman, 2003].…”

“…A second trial was published in 2006 comparing IFN γ -1b and colchicine in IPF [Antoniou et al 2006]. This study enrolled 50 consecutive patients with mild-to-moderate IPF, either with histologically-proven UIP or, in the absence of surgical biopsy, with a a clinical diagnosis of IPF according to the ATS/ERS criteria [ATS/ERS Consensus 2002].…”

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

“…Some of them were retrospective analyses or case series only. Among the drugs tried or on trial are Etanercept, Imatinib, Prednisone (Daniil et al, 1999;Douglas et al, 1997;Douglas, Ryu, & Schroeder, 2000;Douglas et al, 1998;Nicholson AG, 2000;Riha et al, 2002;Ziesche, Hofbauer, Wittmann, Petkov, & Block, 1999), N-Acetylcysteine (Demedts et al, 2005), TGF-β antibody (Genzyme, 2007), Interferon-γ (Antoniou et al, 2006;Raghu et al, 2004;Raghu R, 2001), Interferon-β (Raghu, Bozic, & Brown, 2001), Pirfenidone (Azuma, Nukiwa et al, 2005;S. Nagai et al, 2002;Raghu, Johnson, Lockhart, & Mageto, 1999), Colchicine (Douglas, Ryu, & Schroeder, 2000;Douglas et al, 1998;Selman et al, 1998), Bosentan, Cyclosporin-A (Alton, Johnson, & Turner-Warwick, 1989;Moolman, Bardin, Rossouw, & Joubert, 1991), D-Penicillamin (Chapela, Zuniga, & Selman, 1986;Selman et al, 1998), Heparin (Kubo et al, 2005), Relaxin (ATS, 2002), Angiotensin converting enzyme (ACE) inhibitors (Nadrous, Ryu, Douglas, Decker, & Olson, 2004), and CTGF antibodies (Mageto Y, 2004).…”

Idiopathic pulmonary fibrosis: treatment options in pursuit of evidence-based approaches

“…In the current issue of the European Respiratory Journal, ANTONIOU et al [15] report their observation in a cohort of patients with IPF treated with IFN-c-1b. The investigators prospectively randomised a selected subgroup of patients with IPF (mild-to-moderate functional impairment, based on FVC 55% predicted and DL,CO 35% pred) to receive IFN-c-1b or colchicine and followed their clinical course.…”