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Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency : an open-label extension trial (RAPID-OLE)

McElvaney, Noel G.; Burdon, Jonathan; Holmes, Mark; Glanville, Allan; Wark, Peter A B; Thompson, Philip J.; Hernandez, Paul; Chlumsky, Jan; Teschler, Helmut and Ficker, Joachim H., et al. (2017) In The Lancet Respiratory Medicine 5(1). p.51-60
Abstract

Background Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT. Methods Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint... (More)

Background Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT. Methods Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint was annual rate of adjusted 15th percentile lung density loss measured using CT in the intention-to-treat population with a mixed-effects regression model. This trial is registered with ClinicalTrials.gov, number NCT00670007. Findings Between March 1, 2006, and Oct 13, 2010, 140 patients from RAPID-RCT entered RAPID-OLE: 76 from the early-start group and 64 from the delayed-start group. Between day 1 and month 24 (RAPID-RCT), the rate of lung density loss in RAPID-OLE patients was lower in the early-start group (−1·51 g/L per year [SE 0·25] at total lung capacity [TLC]; −1·55 g/L per year [0·24] at TLC plus functional residual capacity [FRC]; and −1·60 g/L per year [0·26] at FRC) than in the delayed-start group (−2·26 g/L per year [0·27] at TLC; −2·16 g/L per year [0·26] at TLC plus FRC, and −2·05 g/L per year [0·28] at FRC). Between months 24 and 48, the rate of lung density loss was reduced in delayed-start patients (from −2·26 g/L per year to −1·26 g/L per year), but no significant difference was seen in the rate in early-start patients during this time period (−1·51 g/L per year to −1·63 g/L per year), thus in early-start patients the efficacy was sustained to month 48. Interpretation RAPID-OLE supports the continued efficacy of A1PI in slowing disease progression during 4 years of treatment. Lost lung density was never recovered, highlighting the importance of early intervention with A1PI treatment. Funding CSL Behring.

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The Lancet Respiratory Medicine
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5
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10 pages
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Elsevier
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  • scopus:85006324680
  • wos:000396348600026
ISSN
2213-2600
DOI
10.1016/S2213-2600(16)30430-1
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English
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yes
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6dcc403c-f61d-4f57-a6cf-5806f4601028
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2017-01-16 09:43:18
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2018-05-06 04:29:49
@article{6dcc403c-f61d-4f57-a6cf-5806f4601028,
  abstract     = {<p>Background Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT. Methods Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint was annual rate of adjusted 15th percentile lung density loss measured using CT in the intention-to-treat population with a mixed-effects regression model. This trial is registered with ClinicalTrials.gov, number NCT00670007. Findings Between March 1, 2006, and Oct 13, 2010, 140 patients from RAPID-RCT entered RAPID-OLE: 76 from the early-start group and 64 from the delayed-start group. Between day 1 and month 24 (RAPID-RCT), the rate of lung density loss in RAPID-OLE patients was lower in the early-start group (−1·51 g/L per year [SE 0·25] at total lung capacity [TLC]; −1·55 g/L per year [0·24] at TLC plus functional residual capacity [FRC]; and −1·60 g/L per year [0·26] at FRC) than in the delayed-start group (−2·26 g/L per year [0·27] at TLC; −2·16 g/L per year [0·26] at TLC plus FRC, and −2·05 g/L per year [0·28] at FRC). Between months 24 and 48, the rate of lung density loss was reduced in delayed-start patients (from −2·26 g/L per year to −1·26 g/L per year), but no significant difference was seen in the rate in early-start patients during this time period (−1·51 g/L per year to −1·63 g/L per year), thus in early-start patients the efficacy was sustained to month 48. Interpretation RAPID-OLE supports the continued efficacy of A1PI in slowing disease progression during 4 years of treatment. Lost lung density was never recovered, highlighting the importance of early intervention with A1PI treatment. Funding CSL Behring.</p>},
  author       = {McElvaney, Noel G. and Burdon, Jonathan and Holmes, Mark and Glanville, Allan and Wark, Peter A B and Thompson, Philip J. and Hernandez, Paul and Chlumsky, Jan and Teschler, Helmut and Ficker, Joachim H. and Seersholm, Niels and Altraja, Alan and Mäkitaro, Riitta and Chorostowska-Wynimko, Joanna and Sanak, Marek and Stoicescu, Paul I. and Piitulainen, Eeva and Vit, Oliver and Wencker, Marion and Tortorici, Michael A. and Fries, Michael and Edelman, Jonathan M. and Chapman, Kenneth R.},
  issn         = {2213-2600},
  language     = {eng},
  month        = {01},
  number       = {1},
  pages        = {51--60},
  publisher    = {Elsevier},
  series       = {The Lancet Respiratory Medicine},
  title        = {Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency : an open-label extension trial (RAPID-OLE)},
  url          = {http://dx.doi.org/10.1016/S2213-2600(16)30430-1},
  volume       = {5},
  year         = {2017},
}