Survival analysis from the INCREASE study in PH-ILD: Evaluating the impact of treatment crossover on overall mortality

Steven D. Nathan, Shilpa Johri, Joanna M. Joly, Christopher S. King, Amresh Raina, Colleen A. McEvoy, Dasom Lee, Eric Shen, Peter Smith, Chunqin Deng, Aaron B. Waxman

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Objective A post-hoc analysis of the INCREASE trial and its open-label extension (OLE) was performed to evaluate whether inhaled treprostinil has a long-term survival benefit in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). Methods Two different models of survival were employed; the inverse probability of censoring weighting (IPCW) and the rank-preserving structural failure time (RPSFT) models both allow construction of a pseudo-placebo group, thereby allowing for long-term survival evaluation of patients with PH-ILD receiving inhaled treprostinil. Time-varying stabilised weights were calculated by fitting Cox proportional hazards models based on the baseline and time-varying prognostic factors to generate weighted Cox regression models with associated adjusted HRs. Results In the INCREASE trial, there were 10 and 12 deaths in the inhaled treprostinil and placebo arms, respectively, during the 16-week randomised trial. During the OLE, all patients received inhaled treprostinil and there were 29 and 33 deaths in the prior inhaled treprostinil arm and prior placebo arm, respectively. With a conventional analysis, the HR for death was 0.71 (95% CI 0.46 to 1.10; p=0.1227). Both models demonstrated significant reductions in death associated with inhaled treprostinil treatment with HRs of 0.62 (95% CI 0.39 to 0.99; p=0.0483) and 0.26 (95% CI 0.07 to 0.98; p=0.0473) for the IPCW and RPSFT methods, respectively. Conclusion Two independent modelling techniques that have been employed in the oncology literature both suggest a long-term survival benefit associated with inhaled treprostinil treatment in patients with PH-ILD.

Original languageEnglish
Pages (from-to)301-306
Number of pages6
Issue number4
StatePublished - Nov 18 2023


  • Idiopathic pulmonary fibrosis
  • Primary Pulmonary Hypertension
  • Rare lung diseases


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