Using Remote Monitoring Technology to Assess the Therapeutic Efficacy of Imatinib in Patients with Pulmonary Arterial Hypertension

Abstract

Abstract Objective: The aim of this study was to determine a safe, tolerable dose of imatinib for treating patients with idiopathic or heritable pulmonary arterial hypertension (PAH). In addition, the purpose of this study was to assess the clinical efficacy of imatinib administered in escalating doses via remote monitoring technology on patients being treated with a minimum of two PAH therapies Background: Previous studies have suggested that imatinib can improve hemodynamic function and exercise capacity in patients with PAH. However, concerns about safety and tolerability have prevented the development of imatinib as a treatment for PAH. Methods: PIPAH (Positioning Imatinib for Pulmonary Arterial Hypertension), an open- label single-arm study, recruited patients with idiopathic or heritable PAH. The study had two parts; the first part used a Bayesian continuous reassessment method (CRM) to determine the best-tolerated dose of imatinib, ranging from 100 to 400mg. The second part assessed the efficacy of imatinib after 24 weeks of treatment with the best tolerated dose. Results: Three patients underwent implantation of pulmonary artery pressure monitors (CM, CardioMEMS) and an insertable cardiac monitor (ICM, LinQ); no procedure-related serious adverse events were reported. After 12 weeks of imatinib therapy, the mean pulmonary artery pressure was reduced to 45 ± 5 mmHg from 52 ± 7 mmHg (mean ± SD), and cardiac output was elevated to a mean of 5.1± 0.6 L/min from 4.4 ±1.0 L/min (mean ± SD). The six-minute walking distance increased by 65.5 ± 0.5 meters (mean ± SD), and the serum level of N-terminal pro-brain natriuretic peptide was reduced by 480.0 ± 131.4 pg/ml (mean ± SD) in patients after imatinib therapy compared to before treatment. 3 Conclusion: The PIPAH study showed that imatinib, the first drug of a new class of medicines for treating PAH, improves hemodynamic parameters, exercise capacity, and NTpro-BNP level in patients with PAH who remain symptomatic after being treated with dual or triple oral therapy.