Pulmonary Vascular Disease

TOPIC: Pulmonary Vascular Disease

TYPE: Original Investigations

THE IMPACT OF HEMODYNAMIC PARAMETERS ON INHALED TREPROSTINIL TREATMENT

RESPONSE: A SUBGROUP ANALYSIS FROM THE INCREASE TRIAL
AARON WAXMAN VICTOR TAPSON REDA GIRGIS JAMES RUNO REMZI BAG ARUNABH TALWAR PETER
SMITH DANA JOHNSON CHRISTINE PARK AND STEVEN NATHAN

PURPOSE: INCREASE was a 16-week trial evaluating the safety and efficacy of inhaled treprostinil in patients with pulmonary
hypertension associated with interstitial lung disease (PH-ILD). The study met its primary efficacy endpoint of change in six-
minute walk distance (6MWD) and all secondary endpoints. Improvements in the safety endpoint, forced vital capacity (FVC),
were also observed in the treatment group. This post-hoc analysis evaluated the treatment effect of inhaled treprostinil on 6MWD
and FVC as a function of baseline hemodynamics.
METHODS: Multiple regression analyses were conducted to evaluate the impact of hemodynamic parameters on differences
between treatment groups in 6MWD and FVC changes at week 16. Hemodynamic parameters included pulmonary vascular
resistance (PVR) and mean pulmonary artery pressure (mPAP). Baseline PVR and mPAP values ranged from 3.06 – 18.05 Wood
units (WU) and 25 – 74 mmHg, respectively, and were similar between treatment and placebo arms.
RESULTS: All patients with values at baseline and at least one measurement post-baseline were included (n¼302, 6MWD;

PULMONARY VASCULAR DISEASE

n¼287, FVC). There were statistically significant treatment interaction terms for changes in 6MWD with PVR and mPAP. For
every additional 1 WU increase in baseline PVR, 6MWD improved by 4.54 m in the treatment group compared to -3.89 m in the
placebo group (p<0.0001). For every additional 1 mmHg increase in mPAP, 6MWD improved by 0.32 m in the treatment group
compared to -1.18 m in the placebo group (p¼0.0098). Similar trends were observed for changes in FVC, though these results did
not reach statistical significance. For every additional 1 WU increase in PVR, FVC improved by 1.15 mL in the treatment group
compared to -19.72 mL observed in the placebo group (p¼0.0601). For every additional 1 mmHg increase in baseline mPAP, FVC
improved by 0.21 mL in the treatment arm compared to -5.30 mL for those on placebo (p¼0.1206).
CONCLUSIONS: This analysis suggests a positive treatment effect of inhaled treprostinil on 6MWD in PH-ILD patients when
adjusted for baseline hemodynamic characteristics. PH-ILD patients with more severe elevations in PVR derive greater
improvements in exercise capacity likely reflecting improved right ventricular function with inhaled treprostinil. Similar
improvements in FVC could reflect increased cardiac output with resultant improved respiratory muscle function.
CLINICAL IMPLICATIONS: Though the benefit of inhaled treprostinil in 6MWD was observed across the entire range of
reported baseline values, patients with higher PVR and/or mPAP were more likely to have robust responses to treatment. This
analysis suggests higher PVR and mPAP reflect progressive pulmonary vascular remodeling and demonstrates the importance of
considering pulmonary hemodynamics when treating patients with PH-ILD.
DISCLOSURES: No relevant relationships by Remzi Bag, source¼Web Responseresearch relationship with United Therapeutics
Please note: 2016- ongoing Added 04/19/2021 by Reda Girgis, source¼Web Response, value¼Grant/Researchresearch
relationship with Pfizer Please note: 2014-2020 Added 04/19/2021 by Reda Girgis, source¼Web Response, value¼Grant/Research
Speaker/Speaker's Bureau relationship with Boehringher Ingelheim Please note: 2016-ongoing Added 04/19/2021 by Reda Girgis,
source¼Web Response, value¼Honoraria
Speaker/Speaker's Bureau relationship with Genentech Please note: 2016-ongoing Added 04/19/2021 by Reda Girgis, source¼Web
Response, value¼Honoraria
Employee relationship with United Therapeutics Please note: 09/08/2020-now Added 04/26/2021 by Dana Johnson, source¼Web
Response, value¼Salary
Consultant relationship with Veracyte Please note: $1001 - $5000 by Steven Nathan, source¼Web Response, value¼Honoraria
Consultant relationship with United Therapeutics Please note: $5001 - $20000 by Steven Nathan, source¼Web Response,
value¼Consulting fee

chestjournal.org 2265A
 Consultant relationship with Bellerophon Please note: $5001 - $20000 by Steven Nathan, source¼Web Response,
value¼Consulting fee
Speaker/Speaker's Bureau relationship with Roche-Genentech Please note: $5001 - $20000 by Steven Nathan, source¼Web
Response, value¼Honoraria
Speaker/Speaker's Bureau relationship with Boerhinger-Ingelheim Please note: $20001 - $100000 by Steven Nathan, source¼Web
Response, value¼Honoraria
Employee relationship with United Therapeutics Please note: 07/2019 - present Added 04/20/2021 by Christine Park,
source¼Web Response, value¼Salary
No relevant relationships by James Runo, source¼Web Response
Employee relationship with United Therapeutics Please note: >$100000 by Peter Smith, source¼Web Response, value¼Salary
No relevant relationships by Arunabh Talwar, source¼Web Response
Research relationship with Actelion Please note: $1001 - $5000 by Victor Tapson, source¼Web Response, value¼Consulting fee
Research relationship with Janssen Please note: $1001 - $5000 by Victor Tapson, source¼Web Response, value¼Consulting fee
Research support relationship with BMS Please note: $1-$1000 by Victor Tapson, source¼Web Response, value¼Grant/Research
Support
Research support relationship with EKOS Please note: $5001 - $20000 by Victor Tapson, source¼Web Response, value¼Grant/
Research Support
Research support relationship with Inari Please note: $5001 - $20000 by Victor Tapson, source¼Web Response,
value¼Consulting fee
Advisory Committee Member relationship with United Therapeutics Please note: $1001 - $5000 by Victor Tapson, source¼Web
Response, value¼Consulting fee
PULMONARY VASCULAR DISEASE

Consultant relationship with Arena Please note: $1001 - $5000 by Victor Tapson, source¼Web Response, value¼Consulting fee
Advisory Committee Member relationship with United Therapeutics Please note: 2017-present Added 04/21/2021 by Aaron
Waxman, source¼Web Response, value¼Consulting fee
Advisory Committee Member relationship with ARIA CV Please note: 2020-present Added 04/23/2021 by Aaron Waxman,
source¼Web Response, value¼Consulting fee
Advisory Committee Member relationship with Acceleron Please note: 2019-present Added 04/23/2021 by Aaron Waxman,
source¼Web Response, value¼Grant/Research Support
Advisory Committee Member relationship with United Therapeutics Please note: 2015-present Added 04/27/2021 by Aaron
Waxman, source¼Web Response, value¼Grant/Research Support
Advisory Committee Member relationship with Acceleron Please note: 2016-present Added 04/27/2021 by Aaron Waxman,
source¼Web Response, value¼Grant/Research Support
Advisory Committee Member relationship with ARIA CV Please note: 209-present Added 04/27/2021 by Aaron Waxman,
source¼Web Response, value¼Grant/Research Support
Advisory Committee Member relationship with Gossamer Please note: 2016-present Added 04/27/2021 by Aaron Waxman,
source¼Web Response, value¼Grant/Research Support
DOI: https://doi.org/10.1016/j.chest.2021.07.1989
Copyright ª 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

2266A [ 160#4S CHEST OCTOBER 2021 ]