Administration of 120 mg·kg−1 α1-antitrypsin on a biweekly basis was safe and well tolerated http://ow.ly/CVbz30lUBum

α1-antitrypsin (α1-AT) deficiency is a hereditary disorder characterised by an abnormally low concentration of functional α1-AT in blood and tissues [1]. The primary role of α1-AT is to protect elastin-containing tissues, most notably the lung, against the destructive activity of proteolytic enzymes [2]. Patients with severe α1-AT deficiency present with serum α1-AT concentrations <11 μM and are prone to destruction of the lung tissue, often developing respiratory symptoms and emphysema in the fourth or fifth decade of life [3, 4].

A list of the RAPID Trial Group members can be found in the study group information at the end of this article

Clinical Research and Development CSL Behring Bern Switzerland

Clinical Strategy and Development CSL Behring King of Prussia PA USA

conresp Loerzweiler Germany

Dept of Medicine Respiratory and Critical Care Medicine Philipps University Marburg Member of the German Center for Lung Diseases Marburg Germany

Dept of Medicine University of Toronto Toronto ON Canada

Dept of Pulmonary Diseases Charles University Prague Czech Republic

Global Clinical Safety and Pharmacovigilance CSL Behring Marburg Germany

Irish Centre for Genetic Lung disease Beaumont Hospital Royal College of Surgeons in Ireland Dublin Ireland

Statistics Dept CSL Behring King of Prussia PA USA

See more in PubMed

Greene CM, Marciniak SJ, Teckman J, et al. . α1-Antitrypsin deficiency. Nat Rev Dis Primers 2016; 2: 16051. PubMed

Gadek JE, Klein HG, Holland PV, et al. . Replacement therapy of alpha 1-antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects. J Clin Invest 1981; 68: 1158–1165. PubMed PMC

Piras B, Ferrarotti I, Lara B, et al. . Clinical phenotypes of Italian and Spanish patients with α1-antitrypsin deficiency. Eur Respir J 2013; 42: 54–64. PubMed

Greulich T, Nell C, Herr C, et al. . Results from a large targeted screening program for alpha-1-antitrypsin deficiency: 2003 - 2015. Orphanet J Rare Dis 2016; 11: 75. PubMed PMC

Chapman KR, Burdon JG, Piitulainen E, et al. . Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 386: 360–368. PubMed

McElvaney NG, Burdon J, Holmes M, et al. . 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). Lancet Respir Med 2017; 5: 51–60. PubMed

American Thoracic Society, European Respiratory Society. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med 2003; 168: 818–900. PubMed

Sandhaus RA, Turino G, Brantly ML, et al. . The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis 2016; 3: 668–682. PubMed PMC

Miravitlles M, Dirksen A, Ferrarotti I, et al. . European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α1-antitrypsin deficiency. Eur Respir J 2017; 50: 1700610. PubMed

Vidal R, Blanco I, Casas F, et al. . Diagnóstico y tratamiento del déficit de alfa-1-antitripsina [Guidelines for the diagnosis and management of alpha-1 antitrypsin deficiency]. Arch Bronconeumol 2006; 42: 645–659. PubMed

Dirksen A, Dijkman JH, Madsen F, et al. . A randomized clinical trial of α1-antitrypsin augmentation therapy. Am J Respir Crit Care Med 1999; 160: 1468–1472. PubMed

Campos MA, Kueppers F, Stocks JM, et al. . Safety and pharmacokinetics of 120 mg/kg versus 60 mg/kg weekly intravenous infusions of alpha-1 proteinase inhibitor in alpha-1 antitrypsin deficiency: a multicenter, randomized, double-blind, crossover study (SPARK). COPD 2013; 10: 687–695. PubMed

Barker AF, Iwata-Morgan I, Oveson L, et al. . Pharmacokinetic study of α1-antitrypsin infusion in α1-antitrypsin deficiency. Chest 1997; 112: 607–613. PubMed

Tortorici MA, Rogers JA, Vit O, et al. . Quantitative disease progression model of α-1 proteinase inhibitor therapy on computed tomography lung density in patients with α-1 antitrypsin deficiency. Br J Clin Pharmacol 2017; 83: 2386–2397. PubMed PMC

Sorrells S, Camprubi S, Griffin R, et al. . SPARTA clinical trial design: exploring the efficacy and safety of two dose regimens of alpha1-proteinase inhibitor augmentation therapy in alpha1-antitrypsin deficiency. Respir Med 2015; 109: 490–499. PubMed

See more in PubMed

ClinicalTrials.gov
NCT00261833, NCT00670007