ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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Clinical Improvement in Patients Treated with Inhaled Treprostinil: A Post Hoc Analysis of the INCREASE Study
Session Title
TP28 - TP028 APPROACH TO THERAPY IN FIBROSING AND NON-FIBROSING ILD
Abstract
A1911 - Clinical Improvement in Patients Treated with Inhaled Treprostinil: A Post Hoc Analysis of the INCREASE Study
Author Block: A. B. Waxman1, V. F. Tapson2, G. Ramani3, M. G. Risbano4, R. Bourge5, M. Broderick6, P. Smith6, C. Deng6, S. D. Nathan7; 1Center for Pulmonary Heart Disease, Brigham and Woman's Hosp, Boston, MA, United States, 2Pulmonary, Cedars-Sinai, West Hollywood, CA, United States, 3Medicine, University of Maryland, Baltimore, MD, United States, 4Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States, 5University of Alabama, Birmingham, AL, United States, 6United Therapeutics Corporation, Durham, NC, United States, 7Inova Fairfax Hosp, Falls Church, VA, United States.
Background: INCREASE was a 16-week study evaluating the safety and efficacy of inhaled treprostinil versus placebo in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). The study demonstrated that inhaled treprostinil improves exercise capacity, as demonstrated by a 31 meter improvement in six minute walk distance (6MWD) from baseline (260m). This post hoc analysis assessed a composite endpoint of clinical improvement in patients enrolled in the INCREASE study. Methods: The proportion of patients achieving clinical improvement at Week 16 was calculated for both treatment groups. Clinical improvement was defined as the fulfillment of the following 3 criteria at Week 16: 1) the absence of clinical worsening; 2) ≥10% improvement in 6MWD or ≥10% improvement in forced vital capacity (FVC) from baseline; and 3) ≥30% decrease in NT-proBNP from baseline. A sensitivity analysis was conducted to include the absence of an exacerbation of underlying disease as an additional, fourth criterion to define clinical improvement. An exacerbation was defined as investigator-reported, acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality. Differences between groups were evaluated using Fisher’s exact test. Changes in 6MWD, FVC, and NT-proBNP at Week 16 were based on the observed cases; no data were imputed. Results: All 326 patients randomized in INCREASE were included in the present analyses. At Week 16, 16.0% (n=26) of patients in the inhaled treprostinil group demonstrated the composite endpoint of clinical improvement as compared to 5.5% (n=9) in the placebo group (p≤0.0037). Attainment of the second criterion of clinical improvement (≥10% improvement in 6MWD or FVC), was largely driven by improvements in 6MWD, demonstrated by 54 patients in the active group compared to 33 patients in the placebo group demonstrating > 10% improvement in 6MWD from baseline. When the absence of exacerbation of underlying disease was added to the definition of clinical improvement, 12.9% (n= 21) of patients in the inhaled treprostinil group had clinical improvement compared to 4.9% (n=8) in the placebo group (p≤0.0182). Conclusions: In this analysis of patients enrolled in INCREASE, those treated with inhaled treprostinil had a higher likelihood of achieving a composite endpoint of clinical improvement, including improvements in NT-proBNP and 6MWD or FVC at Week 16, when compared to placebo. These analyses further suggest that inhaled treprostinil improves clinical status, with or without exacerbation of underlying lung disease and are consistent with the significant results for the study’s primary endpoint previously reported.
Author Block: A. B. Waxman1, V. F. Tapson2, G. Ramani3, M. G. Risbano4, R. Bourge5, M. Broderick6, P. Smith6, C. Deng6, S. D. Nathan7; 1Center for Pulmonary Heart Disease, Brigham and Woman's Hosp, Boston, MA, United States, 2Pulmonary, Cedars-Sinai, West Hollywood, CA, United States, 3Medicine, University of Maryland, Baltimore, MD, United States, 4Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States, 5University of Alabama, Birmingham, AL, United States, 6United Therapeutics Corporation, Durham, NC, United States, 7Inova Fairfax Hosp, Falls Church, VA, United States.
Background: INCREASE was a 16-week study evaluating the safety and efficacy of inhaled treprostinil versus placebo in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). The study demonstrated that inhaled treprostinil improves exercise capacity, as demonstrated by a 31 meter improvement in six minute walk distance (6MWD) from baseline (260m). This post hoc analysis assessed a composite endpoint of clinical improvement in patients enrolled in the INCREASE study. Methods: The proportion of patients achieving clinical improvement at Week 16 was calculated for both treatment groups. Clinical improvement was defined as the fulfillment of the following 3 criteria at Week 16: 1) the absence of clinical worsening; 2) ≥10% improvement in 6MWD or ≥10% improvement in forced vital capacity (FVC) from baseline; and 3) ≥30% decrease in NT-proBNP from baseline. A sensitivity analysis was conducted to include the absence of an exacerbation of underlying disease as an additional, fourth criterion to define clinical improvement. An exacerbation was defined as investigator-reported, acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality. Differences between groups were evaluated using Fisher’s exact test. Changes in 6MWD, FVC, and NT-proBNP at Week 16 were based on the observed cases; no data were imputed. Results: All 326 patients randomized in INCREASE were included in the present analyses. At Week 16, 16.0% (n=26) of patients in the inhaled treprostinil group demonstrated the composite endpoint of clinical improvement as compared to 5.5% (n=9) in the placebo group (p≤0.0037). Attainment of the second criterion of clinical improvement (≥10% improvement in 6MWD or FVC), was largely driven by improvements in 6MWD, demonstrated by 54 patients in the active group compared to 33 patients in the placebo group demonstrating > 10% improvement in 6MWD from baseline. When the absence of exacerbation of underlying disease was added to the definition of clinical improvement, 12.9% (n= 21) of patients in the inhaled treprostinil group had clinical improvement compared to 4.9% (n=8) in the placebo group (p≤0.0182). Conclusions: In this analysis of patients enrolled in INCREASE, those treated with inhaled treprostinil had a higher likelihood of achieving a composite endpoint of clinical improvement, including improvements in NT-proBNP and 6MWD or FVC at Week 16, when compared to placebo. These analyses further suggest that inhaled treprostinil improves clinical status, with or without exacerbation of underlying lung disease and are consistent with the significant results for the study’s primary endpoint previously reported.
