RAPID: Baseline characteristics may affect response to A1-PI therapy

AUSTIN, TEX. – Higher baseline alpha-1 proteinase inhibitor level, higher body mass index, and female gender may be associated with improved response to alpha-1 proteinase inhibitor augmentation therapy, according to an analysis of data from RAPID.

Better responses to therapy in the trial, as compared with placebo and as measured by mean computed tomography-assessed rate of change in adjusted P15 lung density at total lung capacity, occurred among the 79 female subjects (1.45 g/L per year), and among the 60, 58, and 59 patients with high functional, antigenic, or intermediate functional alpha-1 proteinase inhibitor (A_1-PI) levels, respectively (1.08, 1.23, and 1.38 g/L per year), Dr. James Stocks reported at the annual meeting of the American College of Chest Physicians.

The differences in the rate of change with treatment vs. placebo in these subgroups were statistically significant, said Dr. Stocks of the University of Texas Health Science Center at Tyler.

Greater differences in favor of A1-PI – with a trend toward statistical significance – were also seen in the 21 patients with a body mass index of 30 kg/m² or greater (2.21 g/L per year), the 86 patients under age 54 years (0.96 g/L year), the 87 patients with a carbon monoxide diffusion capacity at or below the median at baseline (0.90 g/L per year), the 8 patients with lower exercise capacity, defined by 400 m or less walked (0.99 g/L per year), and the 88 patients with St. George’s Respiratory Questionnaire symptoms scores at or below the median at baseline (0.93 g/L per year), he said.

RAPID (Randomized, Placebo-Controlled Trial in Alpha-1 Proteinase Inhibitor Deficiency) – the single largest clinical trial of A_1-PI augmentation therapy – included 180 A_1-PI–deficient patients and demonstrated that weekly intravenous A_1-PI therapy at a dose of 60 g/kg per week for 2 years slows progression of emphysema. The annual rate of decline in CT-measured lung density was 34%, compared with placebo. Those findings were reported in May 2013.

According to the current analysis, A_1-PI augmentation appears to be efficacious across a wide range of subgroups, Dr. Stocks said. Those with higher BMI may have experienced greater benefit because of receiving a greater amount of A_1-PI as a result of weight-based dosing. Younger patients may have experienced greater benefit because of being in the earlier stages of disease, with less emphysematous lung damage and lung density loss.

“It is important to note that were no multiplicity adjustments made in the analysis, and no tests for interaction within a subgroup were significant, so no subgroup could be said to be particularly favored as being suitable for treatment with A_1-PI,” he said. It does appear, however, that earlier treatment may help to reduce overall progression of emphysema in affected patients, and that baseline factors such as higher baseline A_1-PI, BMI, and gender may impact treatment benefit, he said.

This study was funded by CSL Behring. Dr. Stocks reported receiving funds as an investigator for the commercially sponsored clinical trial.

AUSTIN, TEX. – Higher baseline alpha-1 proteinase inhibitor level, higher body mass index, and female gender may be associated with improved response to alpha-1 proteinase inhibitor augmentation therapy, according to an analysis of data from RAPID.

Better responses to therapy in the trial, as compared with placebo and as measured by mean computed tomography-assessed rate of change in adjusted P15 lung density at total lung capacity, occurred among the 79 female subjects (1.45 g/L per year), and among the 60, 58, and 59 patients with high functional, antigenic, or intermediate functional alpha-1 proteinase inhibitor (A_1-PI) levels, respectively (1.08, 1.23, and 1.38 g/L per year), Dr. James Stocks reported at the annual meeting of the American College of Chest Physicians.

The differences in the rate of change with treatment vs. placebo in these subgroups were statistically significant, said Dr. Stocks of the University of Texas Health Science Center at Tyler.

Greater differences in favor of A1-PI – with a trend toward statistical significance – were also seen in the 21 patients with a body mass index of 30 kg/m² or greater (2.21 g/L per year), the 86 patients under age 54 years (0.96 g/L year), the 87 patients with a carbon monoxide diffusion capacity at or below the median at baseline (0.90 g/L per year), the 8 patients with lower exercise capacity, defined by 400 m or less walked (0.99 g/L per year), and the 88 patients with St. George’s Respiratory Questionnaire symptoms scores at or below the median at baseline (0.93 g/L per year), he said.

RAPID (Randomized, Placebo-Controlled Trial in Alpha-1 Proteinase Inhibitor Deficiency) – the single largest clinical trial of A_1-PI augmentation therapy – included 180 A_1-PI–deficient patients and demonstrated that weekly intravenous A_1-PI therapy at a dose of 60 g/kg per week for 2 years slows progression of emphysema. The annual rate of decline in CT-measured lung density was 34%, compared with placebo. Those findings were reported in May 2013.

According to the current analysis, A_1-PI augmentation appears to be efficacious across a wide range of subgroups, Dr. Stocks said. Those with higher BMI may have experienced greater benefit because of receiving a greater amount of A_1-PI as a result of weight-based dosing. Younger patients may have experienced greater benefit because of being in the earlier stages of disease, with less emphysematous lung damage and lung density loss.

“It is important to note that were no multiplicity adjustments made in the analysis, and no tests for interaction within a subgroup were significant, so no subgroup could be said to be particularly favored as being suitable for treatment with A_1-PI,” he said. It does appear, however, that earlier treatment may help to reduce overall progression of emphysema in affected patients, and that baseline factors such as higher baseline A_1-PI, BMI, and gender may impact treatment benefit, he said.

This study was funded by CSL Behring. Dr. Stocks reported receiving funds as an investigator for the commercially sponsored clinical trial.

AUSTIN, TEX. – Higher baseline alpha-1 proteinase inhibitor level, higher body mass index, and female gender may be associated with improved response to alpha-1 proteinase inhibitor augmentation therapy, according to an analysis of data from RAPID.

Better responses to therapy in the trial, as compared with placebo and as measured by mean computed tomography-assessed rate of change in adjusted P15 lung density at total lung capacity, occurred among the 79 female subjects (1.45 g/L per year), and among the 60, 58, and 59 patients with high functional, antigenic, or intermediate functional alpha-1 proteinase inhibitor (A_1-PI) levels, respectively (1.08, 1.23, and 1.38 g/L per year), Dr. James Stocks reported at the annual meeting of the American College of Chest Physicians.

The differences in the rate of change with treatment vs. placebo in these subgroups were statistically significant, said Dr. Stocks of the University of Texas Health Science Center at Tyler.

Greater differences in favor of A1-PI – with a trend toward statistical significance – were also seen in the 21 patients with a body mass index of 30 kg/m² or greater (2.21 g/L per year), the 86 patients under age 54 years (0.96 g/L year), the 87 patients with a carbon monoxide diffusion capacity at or below the median at baseline (0.90 g/L per year), the 8 patients with lower exercise capacity, defined by 400 m or less walked (0.99 g/L per year), and the 88 patients with St. George’s Respiratory Questionnaire symptoms scores at or below the median at baseline (0.93 g/L per year), he said.

RAPID (Randomized, Placebo-Controlled Trial in Alpha-1 Proteinase Inhibitor Deficiency) – the single largest clinical trial of A_1-PI augmentation therapy – included 180 A_1-PI–deficient patients and demonstrated that weekly intravenous A_1-PI therapy at a dose of 60 g/kg per week for 2 years slows progression of emphysema. The annual rate of decline in CT-measured lung density was 34%, compared with placebo. Those findings were reported in May 2013.

According to the current analysis, A_1-PI augmentation appears to be efficacious across a wide range of subgroups, Dr. Stocks said. Those with higher BMI may have experienced greater benefit because of receiving a greater amount of A_1-PI as a result of weight-based dosing. Younger patients may have experienced greater benefit because of being in the earlier stages of disease, with less emphysematous lung damage and lung density loss.

“It is important to note that were no multiplicity adjustments made in the analysis, and no tests for interaction within a subgroup were significant, so no subgroup could be said to be particularly favored as being suitable for treatment with A_1-PI,” he said. It does appear, however, that earlier treatment may help to reduce overall progression of emphysema in affected patients, and that baseline factors such as higher baseline A_1-PI, BMI, and gender may impact treatment benefit, he said.

This study was funded by CSL Behring. Dr. Stocks reported receiving funds as an investigator for the commercially sponsored clinical trial.