Opinions and Attitudes of Pulmonologists About Augmentation Therapy in Patients with Alpha-1 Antitrypsin Deficiency. A Survey of the EARCO Group

Abstract

Timm Greulich, 1,* Anna Albert, 1,* Werner Cassel, 2 Tobias Boeselt, 1 Erika Peychev, 1 Andreas Klemmer, 1 Francini Ferrerira, 3 Christian Clarenbach, 4 Maria L Torres-Duran, 5, 6 Alice M Turner, 7 Marc Miravitlles 8 1University Medical Centre Giessen and Marburg, Philipps-University, Department of Medicine, Pulmonary and Critical Care Medicine, Member of the German Centre for Lung Research (DZL), Marburg, Germany; 2University Medical Centre Giessen and Marburg, Philipps-University, Department of Medicine, Pulmonary and Critical Care Medicine, Sleep Disorders Centre, Member of the German Centre for Lung Research (DZL), Marburg, Germany; 3Bioclever, Barcelona, Spain; 4Division of Pulmonology, University Hospital Zurich, Zurich, Switzerland; 5Pneumology Department, Hospital Álvaro Cunqueiro, AS Vigo, Spain; 6Instituto de Investigación Sanitaria Galicia Sur (IISGS), Vigo, Spain; 7Respiratory Medicine, University Hospitals Birmingham NHS Foundation Trust, Institute of Applied Health Research, University of Birmingham, Birmingham, UK; 8Pneumology Department, Hospital Universitari Vall d´Hebron/Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain*These authors contributed equally to this workCorrespondence: Marc MiravitllesPneumology Department, Vall d´Hebron Barcelona Hospital Campus, P. Vall d’Hebron 119-129, Barcelona, 08035, SpainTel/Fax [phone]Email [email protected]: Augmentation therapy (AT) is the only specific treatment licensed for patients with alpha-1 antitrypsin deficiency (AATD) associated lung disease. Since patients with severe AATD may have a very different prognosis and AT requires intravenous infusions for life, the decision to initiate AT may be challenging.Methods: This survey was conducted on 63 experts in AATD from 13 European countries about their opinions and attitudes regarding AT. Participants were asked to rank the importance of 11 identified factors related with the prescription of AT. In addition, each participant was asked to respond to the indication of AT for 30 out of 500 hypothetical cases developed with the combinations of the 11 factors. Each case was evaluated by 3 experts to check the concordance.Results: The variables that scored higher on preferences for initiating AT were AAT genotype (score 8.6 from a Likert scale 0– 10 (SD: 1.7)), AATD serum level (8.2 (SD:2.4)) and FEV1 (%) decline (7.9 (SD:2.4)). Among the 500 different cases, there was an agreement in indication of AT among the 3 experts in 291 (58.2%). Regarding the variables associated with AT, it was indicated to 81.9% of Pi*ZZ, 52.4% of Pi*SZ and 9.8% of Pi*MZ (p < 0.0001). For Pi*ZZ patients, multivariate analysis identified younger age, reduced FEV1 (%), higher FEV1 decline and worse emphysema as significantly associated with prescription (AUC = 0.8114); for Pi*SZ variables were younger age, worse FEV1 (%) and worse emphysema (AUC = 0.7414); and for Pi*MZ younger age, worse DLCO (%), higher DLCO decline and dyspnea (AUC = 0.8387).Conclusion: There is a high variability in the criteria for prescription of AT among European experts. Most cases were recommended AT according to guidelines, but a significant number of patients with genotype Pi*SZ and almost 10% Pi*MZ were recommended to initiate AT despite the lack of evidence of efficacy in these genotypes.Keywords: augmentation therapy, survey, EARCO, Europe

Keywords

• augmentation therapy
• survey
• earco
• europe