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Allergy and Airway |

Baseline Patient Demographics and Lung Density Decline in the RAPID Trial FREE TO VIEW

James Stocks; Robert Sandhaus; Kenneth Chapman; Jonathan Burdon; Eeva Piitulainen; Niels Seersholm; Liping Huang; Jonathan Edelman; N. Gerard McElvaney
Author and Funding Information

Pulmonary and Critical Care, University of Texas Health Science Center at Tyler, Tyler, TX


Chest. 2014;146(4_MeetingAbstracts):71A. doi:10.1378/chest.1993054
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Abstract

SESSION TITLE: COPD Treatment

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, October 26, 2014 at 01:30 PM - 03:00 PM

PURPOSE: RAPID (Randomized, placebo-controlled trial in Alpha-1 Proteinase Inhibitor Deficiency, NCT00261833) was the single largest clinical trial of alpha-1 proteinase inhibitor (A1-PI) augmentation therapy, including 180 A1-PI-deficient patients. RAPID demonstrated that A1-PI therapy (Zemaira®, CSL Behring, 60 mg/kg/week) slows progression of emphysema, as assessed by CT lung densitometry. Here we evaluate the effects of baseline parameters on change in lung density at study end.

METHODS: Subjects received A1-PI or placebo for 2 years. The primary endpoint was CT-measured lung density. The effects of baseline parameters on the mean annual rate of change in adjusted P15 lung density (g/L/y) at total lung capacity were investigated in the intention-to-treat population (N=180) by analyzing the lung density decline in each of several subgroups.

RESULTS: The strongest treatment differences in favor of A1-PI were observed for females (n=79, 1.45 g/L/y; p=0.004), and subjects with high (>66 percentile) functional (n=60, 1.08 g/L/y; p=0.022) or antigenic A1-PI levels (n=58, 1.23 g/L/y; p=0.016), or intermediate functional A1-PI levels (33-66 percentile, n=59; 1.38 g/L/y; p=0.025). Subjects with higher BMI (≥30 kg/m2, n=21; 2.21 g/L/y), lower age (<54 years, n=86; 0.97 g/L/y), lower DLCO (≤ median at baseline, n=87; 0.90 g/L/y), lower exercise capacity (≤ 400 m walked, n=88; 0.99 g/L/y), or lower SGRQ symptoms score (≤ median at baseline, n=88; 0.93 g/L/y) also tended to show greater differences in favor of A1-PI.

CONCLUSIONS: A1-PI augmentation was efficacious across a wide range of subgroups. Patients with higher baseline antigenic/functional A1-PI levels had greater reductions in lung density decline vs. placebo than did those with lower baseline levels. Patients with higher BMI tended to have a greater treatment benefit, possibly due to the greater amount of A1-PI they received. Younger patients tended to have a greater treatment benefit, possibly because they were in the earlier stages of disease and had less emphysematous lung damage/lung density loss.

CLINICAL IMPLICATIONS: A1-PI therapy appears to be beneficial in reducing the rate of lung density decline in A1-PI-deficient patients presenting with diverse baseline characteristics; some characteristics seem to be associated with greater treatment benefit.

DISCLOSURE: James Stocks: Other: Received funds as an investigator on a commercially sponsored clinical trial Robert Sandhaus: Other: Received funds as an investigator on a commercially sponsored clinical trial Kenneth Chapman: Other: Received funds as an investigator on a commercially sponsored clinical trial Jonathan Burdon: Other: Received funds as an investigator on a commercially sponsored clinical trial Eeva Piitulainen: Other: Received funds as an investigator on a commercially sponsored clinical trial Niels Seersholm: Other: Received funds as an investigator on a commercially sponsored clinical trial Liping Huang: Employee: Employed by CSL Behring Jonathan Edelman: Employee: Employed by CSL Behring N. Gerard McElvaney: Other: Received funds as an investigator on a commercially sponsored clinical trial

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