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.

Asthma and Airway Centre University Health Network and University of Toronto Toronto Canada

Beaumont Hospital Royal College of Surgeons in Ireland Dublin Ireland

conresp Mainz Germany

CSL Behring Bern Switzerland

CSL Behring King Of Prussia PA USA

Dalhousie University Division of Respirology Halifax NS Canada

Department of Respiratory Medicine Allergology and Sleep Medicine General Hospital Nuernberg Nuremberg Germany

Gentofte Hospital Pulmonary Department Y Hellerup Denmark

Hunter Medical Research Institute Centre for Asthma and Respiratory Disease New Lambton NSW Australia

Institute of Respiratory Medicine and School of Medicine and Pharmacology University of Western Australia Crawley WA Australia

Jagiellonian University Medical College Division of Molecular Biology and Clinical Genetics Krakow Poland

National Institute of Tuberculosis and Lung Diseases Department of Genetics and Clinical Immunology Warsaw Poland

Oulu University Hospital Department of Internal Medicines Oulu Finland

Ruhrlandklinik Department of Pneumology West German Lung Center University Hospital Essen University Duisburg Essen Essen Germany

Sanador S A Clinical Central Medical Clinica 2 Bucharest Romania

Skane University Hospital Department of Respiratory Medicine Lund University Malmö Sweden

St Vincent's Hospital Department of Lung Transplantation and Thoracic Medicine Darlinghurst NSW Australia

St Vincent's Hospital Department of Respiratory Medicine Fitzroy VIC Australia

Thomayer Hospital 1st Medical Faculty Charles University Department of Pulmonary Diseases Prague Czech Republic

University of Adelaide and Royal Adelaide Hospital Department of Thoracic Medicine Respiratory Clinical Trials Unit Adelaide SA Australia

University of Tartu Department of Pulmonary Medicine Tartu Estonia

Lancet Respir Med. 2017 Jan;5(1):7-8. doi: 10.1016/S2213-2600(16)30434-9. PubMed

Lancet Respir Med. 2017 Feb;5(2):e13. doi: 10.1016/S2213-2600(17)30004-8. PubMed

References provided by Crossref.org

Diagnosis and management of α1-antitrypsin deficiency in Europe: an expert survey

Safety of biweekly α1-antitrypsin treatment in the RAPID programme

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ClinicalTrials.gov
NCT00670007