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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: Lancet Respiratory Medicine, 2017; 5(1):51-60
Publisher: Elsevier
Issue Date: 2017
ISSN: 2213-2600
Statement of
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, 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.
RMID: 0030062724
DOI: 10.1016/S2213-2600(16)30430-1
Appears in Collections:Medicine publications

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