TY - JOUR
T1 - Inhaled Treprostinil Dosage in Pulmonary Hypertension Associated With Interstitial Lung Disease and Its Effects on Clinical Outcomes
AU - Nathan, Steven D.
AU - Deng, Chunqin
AU - King, Christopher S.
AU - DuBrock, Hilary M.
AU - Elwing, Jean
AU - Rajagopal, Sudarshan
AU - Rischard, Franz
AU - Sahay, Sandeep
AU - Broderick, Meredith
AU - Shen, Eric
AU - Smith, Peter
AU - Tapson, Victor F.
AU - Waxman, Aaron B.
N1 - Funding Information:
The INCREASE study was sponsored by United Therapeutics Corporation but this manuscript was not funded by any entity. S. R. is supported by the National Heart, Lung, and Blood Institute [Grant R01HL153872], the National Institute of General Medical Sciences [Grant R01GM122798], and the American Heart Association [Grant TPA34880033]. F. R. is supported by the National Institutes of Health and the National Heart, Lung, and Blood Institute. V. F. T. is supported by the National Institutes of Health.
Publisher Copyright:
© 2022 The Author(s)
PY - 2023/2
Y1 - 2023/2
N2 - Background: Pulmonary hypertension (PH) complicates the course of many patients with fibrotic interstitial lung disease (ILD). Inhaled treprostinil (iTre) has been shown to improve functional ability and to delay clinical worsening in patients with PH resulting from ILD. Research Question: Do higher dosages of iTre have greater benefits in preventing clinical worsening and achieving clinical improvement? Study Design and Methods: Post hoc analysis of the INCREASE study, a 16-week double-blind, randomized, placebo-controlled trial of iTre in patients with PH resulting from ILD. Four groups were identified based on the number of breaths per session (bps; < 9 and ≥ 9 bps) of active drug or placebo attained at 4 weeks. Patients were evaluated for clinical worsening (15% decrease in 6-min walkdistance, cardiopulmonary hospitalization, lung transplantation, or death) or clinical improvement (15% increase in the six-minute walk distance with a concomitant 30% reduction in N-terminal prohormone of brain natriuretic peptide without any clinical worsening event). Results: At 4 weeks, 70 patients were at a dose of ≥ 9 bps (high-dosage group) and 79 patients were at a dose of < 9 bps (low-dosage group) in the iTre arm vs 86 patients in the high-dose group and 67 patients in the low-dose group in the placebo arm. Between weeks 4 and 16, 17.1% of patients in the high-dose treprostinil group and 22.8% in the low-dose treatment group experienced a clinical worsening event vs 33.7% and 34.3% of patients in the two placebo arms, respectively (P = .006). By week 16, 15.7% and 12.7% of patients in the high- and low-dose iTre groups, respectively, demonstrated clinical improvement vs 7% and 1.5% patients in the placebo arms (P = .003) Interpretation: Higher dosages of iTre overall show greater benefit in terms of preventing clinical worsening and achieving clinical improvement. These data support the early initiation and uptitration of therapy to a dosage of at least 9 bps four times daily in patients with PH resulting from ILD. Trial Registry: ClinicalTrials.gov; No.: NCT02630316; URL: www.clinicaltrials.gov
AB - Background: Pulmonary hypertension (PH) complicates the course of many patients with fibrotic interstitial lung disease (ILD). Inhaled treprostinil (iTre) has been shown to improve functional ability and to delay clinical worsening in patients with PH resulting from ILD. Research Question: Do higher dosages of iTre have greater benefits in preventing clinical worsening and achieving clinical improvement? Study Design and Methods: Post hoc analysis of the INCREASE study, a 16-week double-blind, randomized, placebo-controlled trial of iTre in patients with PH resulting from ILD. Four groups were identified based on the number of breaths per session (bps; < 9 and ≥ 9 bps) of active drug or placebo attained at 4 weeks. Patients were evaluated for clinical worsening (15% decrease in 6-min walkdistance, cardiopulmonary hospitalization, lung transplantation, or death) or clinical improvement (15% increase in the six-minute walk distance with a concomitant 30% reduction in N-terminal prohormone of brain natriuretic peptide without any clinical worsening event). Results: At 4 weeks, 70 patients were at a dose of ≥ 9 bps (high-dosage group) and 79 patients were at a dose of < 9 bps (low-dosage group) in the iTre arm vs 86 patients in the high-dose group and 67 patients in the low-dose group in the placebo arm. Between weeks 4 and 16, 17.1% of patients in the high-dose treprostinil group and 22.8% in the low-dose treatment group experienced a clinical worsening event vs 33.7% and 34.3% of patients in the two placebo arms, respectively (P = .006). By week 16, 15.7% and 12.7% of patients in the high- and low-dose iTre groups, respectively, demonstrated clinical improvement vs 7% and 1.5% patients in the placebo arms (P = .003) Interpretation: Higher dosages of iTre overall show greater benefit in terms of preventing clinical worsening and achieving clinical improvement. These data support the early initiation and uptitration of therapy to a dosage of at least 9 bps four times daily in patients with PH resulting from ILD. Trial Registry: ClinicalTrials.gov; No.: NCT02630316; URL: www.clinicaltrials.gov
KW - interstitial lung disease
KW - prostacyclin
KW - pulmonary hypertension
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U2 - 10.1016/j.chest.2022.09.007
DO - 10.1016/j.chest.2022.09.007
M3 - Article
C2 - 36115497
AN - SCOPUS:85145165952
VL - 163
SP - 398
EP - 406
JO - CHEST
JF - CHEST
SN - 0012-3692
IS - 2
ER -