Development and Validation of a Scoring System for Prediction of Tolerance to Inhaled Treprostinil in Patients with PAH or PH-ILD

<b>Background</b>: Treprostinil has demonstrated effectiveness in treating Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension associated with Interstitial Lung Disease (PH-ILD). However, tolerability remains a clinical challenge. Identifying factors influencing tolerability is important, given the adverse outcomes of PAH and PH-ILD and the potential of treprostinil to slow disease progression. Objective: This study was undertaken to identify tolerance factors and develop a predictive scoring system. <b>Methods</b>: A retrospective analysis of 65 patients (37 PAH, 28 PH-ILD) was conducted using patient history, pulmonary function tests (PFTs), transthoracic echocardiograms (TTEs), and right heart catheterizations (RHCs). Of these, 67.7% (<i>n</i> = 44) tolerated treprostinil, while 32.3% (<i>n</i> = 21) were intolerant. <b>Results</b>: Patients who tolerated treprostinil had better pulmonary function, with a higher forced expiratory volume in one second/forced vital capacity (FEV₁/FVC) ratio (82.27 ± 16.06 vs. 72.86 ± 17.76, <i>p</i> = 0.037) and superior right ventricular function, as indicated by higher tricuspid annular plane systolic excursion (TAPSE: 2.05 ± 0.37 vs. 1.64 ± 0.42, <i>p</i> < 0.001), higher cardiac index (CI: 2.51 ± 0.67 vs. 2.03 ± 0.53, <i>p</i> = 0.003), and improved functional status (<i>p</i> < 0.001). The Inhaled Treprostinil Intolerance Score (ITIS), incorporating TAPSE < 1.6, CI < 2, FEV₁/FVC < 70%, and WHO functional class (FC) 3 or 4, demonstrated strong predictive accuracy (cutoff ≥ 2, AUC = 0.884 ± 0.048, <i>p</i> < 0.001). Predictive performance was stronger in PAH patients (AUC = 0.921 ± 0.053) than PH-ILD (AUC = 0.833 ± 0.093, <i>p</i> < 0.001). <b>Conclusions</b>: These findings demonstrate the importance of clinical parameters in predicting treprostinil tolerance. Further investigation is warranted to refine the scoring system, particularly for PH-ILD patients.