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https://hdl.handle.net/2440/104779
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Type: | Journal article |
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) |
Author: | McElvaney, N. Burdon, J. Holmes, M. Glanville, A. Wark, P. Thompson, P. Hernandez, P. Chlumsky, J. Teschler, H. Ficker, J. Seersholm, N. Altraja, A. Mäkitaro, R. Chorostowska-Wynimko, J. Sanak, M. Stoicescu, P. Piitulainen, E. Vit, O. Wencker, M. Tortorici, M. et al. |
Citation: | The Lancet Respiratory Medicine, 2017; 5(1):51-60 |
Publisher: | Elsevier |
Issue Date: | 2017 |
ISSN: | 2213-2600 2213-2619 |
Statement of Responsibility: | Noel G McElvaney, Jonathan Burdon, Mark Holmes, Allan Glanville, Peter A B Wark, Philip J Thompson … et al. |
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 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. |
Keywords: | RAPID Extension Trial Group Lung Humans Pulmonary Emphysema alpha 1-Antitrypsin Deficiency Disease Progression alpha 1-Antitrypsin Serine Proteinase Inhibitors Respiratory Function Tests Total Lung Capacity Treatment Outcome Regression Analysis Adolescent Adult Female Male Young Adult |
Rights: | Copyright ©2017. Elsevier Inc. All rights reserved. |
DOI: | 10.1016/S2213-2600(16)30430-1 |
Published version: | http://dx.doi.org/10.1016/s2213-2600(16)30430-1 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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