- 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)
- Creator
- McElvaney, Noel G.; Burdon, Jonathan; Seersholm, Niels; Altraja, Alan; Mäkitaro, Riita; Chorostowska-Wynimko, Joanna; Sanak, Marek; Stoicescu, Paul I.; Piitulainen, Eeva; Vit, Oliver; Wencker, Marion; Tortorici, Michael A.; Holmes, Mark; Fries, Michael; Edelman, Jonathan M.; Chapman, Kenneth R.; Glanville, Allan; Wark, Peter A. B.; Thompson, Philip J.; Hernandez, Paul; Chlumsky, Jan; Teschler, Helmut; Ficker, Joachim H.
- Relation
- Lancet Respiratory Medicine Vol. 5, Issue 1, p. 51-60
- Publisher Link
- http://dx.doi.org/10.1016/S2213-2600(16)30430-1
- Publisher
- Lancet Publishing
- Resource Type
- journal article
- Date
- 2017
- Description
- 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.
- Subject
- α1 proteinase inhibitor; α1 proteinase inhibitor treatment; emphysema; randomised controlled trial; lung density
- Identifier
- http://hdl.handle.net/1959.13/1399137
- Identifier
- uon:34534
- Identifier
- ISSN:2213-2600
- Language
- eng
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