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)

• Published in: The lancet respiratory medicine Vol. 5; no. 1; pp. 51 - 60
• Main Authors: McElvaney, Noel G, Prof, Burdon, Jonathan, MD, Holmes, Mark, Prof, Glanville, Allan, Prof, Wark, Peter A B, MD, Thompson, Philip J, Prof, Hernandez, Paul, MD, Chlumsky, Jan, MD, Teschler, Helmut, Prof, Ficker, Joachim H, Prof, Seersholm, Niels, MD, Altraja, Alan, Prof, Mäkitaro, Riitta, MD, Chorostowska-Wynimko, Joanna, Prof, Sanak, Marek, Prof, Stoicescu, Paul I, Prof, Piitulainen, Eeva, MD, Vit, Oliver, MSc, Wencker, Marion, MD, Tortorici, Michael A, PhD, Fries, Michael, PhD, Edelman, Jonathan M, MD, Chapman, Kenneth R, MD
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-01-2017
• Subjects: Adolescent; Adult; alpha 1-Antitrypsin - administration & dosage; alpha 1-Antitrypsin Deficiency - complications; alpha 1-Antitrypsin Deficiency - pathology; Clinical Medicine; Disease Progression; Female; Humans; Kirurgi; Klinisk medicin; Lung - pathology; Lung - physiopathology; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Pulmonary Emphysema - congenital; Pulmonary Emphysema - drug therapy; Pulmonary Emphysema - pathology; Pulmonary/Respiratory; Regression Analysis; Respiratory Function Tests; Serine Proteinase Inhibitors - administration & dosage; Surgery; Total Lung Capacity; Treatment Outcome; Young Adult
• ISSN: 2213-2600; 2213-2619
• DOI: 10.1016/S2213-2600(16)30430-1

Summary 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.