Derivation of a simple risk calculator for predicting clinical worsening in patients with pulmonary hypertension due to interstitial lung disease

SESSION TITLE: Pulmonary Vascular Disease Posters 2 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2023 12:00 pm - 12:45 pm PURPOSE: The prognosis associated with pulmonary hypertension due to interstitial lung disease (PH-ILD) is dismal, with a median survival of 1.5 to 2 years. At present, there is no clinical tool to assess the risk of poor clinical outcomes in this patient population. Our aim was to derive a simple and practical risk calculator that could be used to predict risk of clinical worsening in patients with PH-ILD. METHODS: The INCREASE study was a 16-week study that evaluated inhaled treprostinil in patients with PH-ILD. Placebo arm data were used to derive a risk calculator. Patients with missing baseline data were excluded. The outcome of interest was clinical worsening, defined as time to cardiopulmonary hospitalization, >15% decrease in 6MWD, death, or lung transplantation. Two Cox models adjusting for different combinations of baseline characteristics were identified using stepwise regression (a variable selection technique), Harrell’s c-index, and clinician input. Thresholds were then applied to the Cox models and were fit adjusted for the categorical versions of the variables. Points were assigned to thresholds based on regression estimates. Final Cox models were adjusted for total point score. Total scores were grouped into 3 stages: low, intermediate, and high risk. Model discrimination was assessed by bias-corrected estimates of the c-index. RESULTS: Two risk calculators were derived – one “non-invasive” and one “invasive” from 147 and 146 placebo patients, respectively, with 44 patients experiencing a clinical worsening event in both cases. The non-invasive risk calculator uses NT-proBNP and % predicted FVC/ DLCO ratio and predicts the risk of clinical worsening: low risk (<25%, 0-1 points); intermediate risk (25-50%, 2-3 points); high risk (>50%, 4 points). The invasive risk calculator adds on cardiac index and predicts risk of clinical worsening as follows: low risk (<20%, 0-2 points); intermediate risk (20-50%, 3-6 points); high risk (>50%, 7-10 points). The estimated c-index was 0.683 (95% CI: 0.612, 0.761) for the non-invasive point score model and 0.703 (95% CI: 0.635, 0.783) for the invasive total point score model. CONCLUSIONS: We describe two versions of a simple model to risk stratify patients for clinical worsening within 16 weeks with clinically useful discrimination. The non-invasive calculator performed similarly to the invasive calculator and utilizes variables that are easily collected. Interestingly, the addition of 6MWD to models did not improve their performance. While use of these risk calculators should not dictate therapy, it does help clinicians in providing important prognostic information which can be used to reinforce the benefits of therapy. Limitations of our risk calculator is the 16-week duration of the INCREASE trial, which prevent longer term outcomes from being assessed. Future work could involve validation of our risk tool on an external patient population over a longer time period including application to the INCREASE open-label extension population. CLINICAL IMPLICATIONS: This risk calculator is simple to use in clinic, utilizing variables that are commonly collected to gauge the risk of clinical worsening over 16-weeks in patients with PH-ILD. DISCLOSURES: Research Support relationship with Medtronic Please note: 2016- Current by Remzi Bag, value=Grant/Research Research Support relationship with PhaseBio Please note: 2017-2021 by Remzi Bag, value=Grant/Research Support Research Support relationship with United Therapeutics Please note: 2016-current by Remzi Bag, value=Grant/Research Support Research Support relationship with Liquidia Technologies Please note: 2018-2021 by Remzi Bag, value=Grant/Research Support Research Support relationship with Actelion/ Janssen Please note: 2016-Current by Remzi Bag, value=Grant/Research No relevant relationships by Nitin Bhatt Employee relationship with United Therapeutics Please note: 09/08/2020-now by Dana Cella, value=Salary Consultant relationship with J&J Actelion Please note: Current Added 03/30/2023 by Karim El-Kersh, source=Web Response, value=Consulting fee Consultant relationship with Merck Please note: Current Added 03/30/2023 by Karim El-Kersh, source=Web Response, value=Consulting fee Consultant relationship with United Therapeutics Please note: Current Added 03/30/2023 by Karim El-Kersh, source=Web Response, value=Consulting fee No relevant relationships by Hyoshin Kim Speaker relationship with United Therapeutics Please note: 2021 -present Added 03/30/2023 by Christopher King, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Roche-Genentech Please note: $5001 - $20000 by Steven Nathan, value=Honoraria Speaker/Speaker's Bureau relationship with Boerhinger-Ingelheim Please note: $20001 - $100000 by Steven Nathan, value=Honoraria Advisory Committee Member relationship with Merck Please note: 2021-2022 Added 11/16/2022 by Steven Nathan, source=Web Response, value=Consulting fee Consultant relationship with Bellerophon Please note: $5001 - $20000 by Steven Nathan, value=Consulting fee Consultant relationship with United Therapeutics Please note: $5001 - $20000 by Steven Nathan, value=Consulting fee Employee relationship with United Therapeutics Corp Please note: >$100000 by Eric Shen, value=Salary Advisory Committee Member relationship with United Therapeutics Please note: 2017-present Added 03/31/2023 by Aaron Waxman, value=Grant/Research Support Advisory Committee Member relationship with ARIA CV Please note: 2020-present Added 03/31/2023 by Aaron Waxman, value=Grant/Research Support Advisory Committee Member relationship with Acceleron Please note: 2019-present by Aaron Waxman, value=Grant/Research Support Advisory Committee Member relationship with United Therapeutics Please note: 2015-present by Aaron Waxman, value=Grant/Research Support Advisory Committee Member relationship with Acceleron Please note: 2016-present by Aaron Waxman, value=Grant/Research Support Advisory Committee Member relationship with ARIA CV Please note: 209-present by Aaron Waxman, value=Grant/Research Support Advisory Committee Member relationship with Gossamer Please note: 2016-present by Aaron Waxman, value=Grant/Research Support