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).
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  CSL Behring.
authors.affiliation: Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland. Electronic address: gmcelvaney@rcsi.ie.
authors.forename: Noel G
authors.initials: NG
authors.lastname: McElvaney
authors.affiliation: St Vincent's Hospital, Department of Respiratory Medicine, Fitzroy, VIC, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Burdon
authors.affiliation: University of Adelaide and Royal Adelaide Hospital, Department of Thoracic Medicine, Respiratory Clinical Trials Unit, Adelaide, SA, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Holmes
authors.affiliation: St Vincent's Hospital, Department of Lung Transplantation and Thoracic Medicine, Darlinghurst, NSW, Australia.
authors.forename: Allan
authors.initials: A
authors.lastname: Glanville
authors.affiliation: Hunter Medical Research Institute, Centre for Asthma and Respiratory Disease, New Lambton, NSW, Australia.
authors.forename: Peter A B
authors.initials: PA
authors.lastname: Wark
authors.affiliation: Institute of Respiratory Medicine & School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Thompson
authors.affiliation: Dalhousie University, Division of Respirology, Halifax, NS, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Hernandez
authors.affiliation: Thomayer Hospital, First Medical Faculty, Charles University, Department of Pulmonary Diseases, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Chlumsky
authors.affiliation: Ruhrlandklinik, Department of Pneumology, West German Lung Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Teschler
authors.affiliation: Department of Respiratory Medicine, Allergology and Sleep Medicine, General Hospital Nuernberg, Nuremberg, Germany.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ficker
authors.affiliation: Gentofte Hospital, Pulmonary Department Y, Hellerup, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Seersholm
authors.affiliation: University of Tartu, Department of Pulmonary Medicine, Tartu, Estonia.
authors.forename: Alan
authors.initials: A
authors.lastname: Altraja
authors.affiliation: Oulu University Hospital, Department of Internal Medicines, Oulu, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Mäkitaro
authors.affiliation: National Institute of Tuberculosis and Lung Diseases, Department of Genetics and Clinical Immunology, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Chorostowska-Wynimko
authors.affiliation: Jagiellonian University Medical College, Division of Molecular Biology and Clinical Genetics, Krakow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
authors.affiliation: Sanador S A Clinical, Central Medical Clinica II, Bucharest, Romania.
authors.forename: Paul I
authors.initials: PI
authors.lastname: Stoicescu
authors.affiliation: Skane University Hospital, Department of Respiratory Medicine, Lund University, Malmö, Sweden.
authors.forename: Eeva
authors.initials: E
authors.lastname: Piitulainen
authors.affiliation: CSL Behring, Bern, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Vit
authors.affiliation: conresp, Mainz, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Wencker
authors.affiliation: CSL Behring, King Of Prussia, PA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tortorici
authors.affiliation: CSL Behring, King Of Prussia, PA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Fries
authors.affiliation: CSL Behring, King Of Prussia, PA, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Edelman
authors.affiliation: Asthma & Airway Centre, University Health Network and University of Toronto, Toronto, Canada.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chapman
mesh_terms: D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011656:Pulmonary Emphysema / Q000151:congenital / Q000188:drug therapy* / Q000473:pathology; D012044:Regression Analysis; D012129:Respiratory Function Tests; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage*; D014109:Total Lung Capacity; D016896:Treatment Outcome; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage*; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications* / Q000473:pathology
chemical_list: D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin