Augmentation therapy with alpha1-antitrypsin: patterns of use and adverse events.
OBJECTIVE
To describe patterns of prescribing augmentation therapy, and types and rates of adverse events in the National Heart, Lung, and Blood Institute Registry for Individuals with Severe Deficiency of Alpha(1)-Antitrypsin.


METHODS
Observational cohort study with follow-up visits every 6 to 12 months for up to 7 years.


METHODS
The rate and dosing frequency with which Registry participants were prescribed to receive augmentation therapy by their managing physicians, and the type and frequency of adverse events, classified in two ways: severity of self-reported symptoms, and actions taken as a consequence of the symptom.


RESULTS
Over the course of Registry follow-up, 66% (n = 747) of the participants received augmentation therapy at some time. In keeping with recommendations made in the 1989 American Thoracic Society (ATS) statement, 75% of participants with airflow obstruction at first visit (defined as FEV(1) < 80% predicted) received augmentation therapy within 3 years, though some participants with FEV(1) > or = 80% predicted (14%) also received augmentation therapy. Among those with COPD for whom augmentation therapy was not prescribed, financial constraints were the reported cause in 30%. Observed patterns also varied from approved practice, in that dosing frequencies other than the US Food and Drug Administration-approved, once-weekly regimen were frequently prescribed. The overall rate of reported adverse events was 0.02 per patient-month, with 83% of participants reporting no events. This overall rate was composed of 16% considered mild events, 76% moderate events, and 9% severe events.


CONCLUSIONS
We conclude that augmentation therapy was generally well tolerated and, consistent with ATS guidelines, physicians generally did not prescribe augmentation therapy for subjects with FEV(1) > or = 80% predicted. However, the large percentage of subjects with FEV(1) <80% predicted not receiving augmentation therapy and the frequent use of 2- to 3-week or monthly dosing reflects variation of practice from suggested treatment guidelines.
Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, OH, USA.
James K
JK
Stoller
Robert
R
Fallat
Mark D
MD
Schluchter
Ralph G
RG
O'Brien
Jason T
JT
Connor
Nicholas
N
Gross
Kevin
K
O'Neil
Robert
R
Sandhaus
Ronald G
RG
Crystal
D001993:Bronchodilator Agents / Q000627:therapeutic use; D004363:Drug Utilization; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D012042:Registries; D000515:alpha 1-Antitrypsin / Q000009:adverse effects / Q000627:therapeutic use*; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications / Q000188:drug therapy*
D001993:Bronchodilator Agents; D000515:alpha 1-Antitrypsin