Imatinib for pulmonary arterial hypertension was the first antiproliferative approach in this condition’s treatment and may still be relevant today despite its complicated history. Originally developed as a cancer therapy (tyrosine kinase inhibitor), it showed very good results in pulmonary arterial hypertension, creating a lot of expectation when the IMPRES study was presented at the 2011 European Respiratory Society (ERS) Congress in Amsterdam. Though the company ultimately withdrew its marketing authorisation application due to serious side effects (including cases cases of subdural hematoma), interest persists.
A group of researchers at Imperial College UK has conducted a dose-finding trial, the results of which were published on the American Journal for Respiratory Critical Care Medicine in March 2025. This study evaluated different doses of oral imatinib as an add-on therapy for pulmonary arterial hypertension patients. Using a Continuous Reassessment Method with 17 patients (13 with implanted monitoring devices), researchers determined that 200mg daily was the recommended starting dose.
Key findings:
- Most common side effect: nausea
- Significant reductions in mean pulmonary artery pressure (-6.5 mmHg) and total pulmonary resistance (-2.8 Wood Units)
- No significant change in cardiac output
- Dose-dependent response with 200mg daily reducing total pulmonary resistance by 20.3%
- Effects developed over 28 days and persisted up to 40 days after discontinuation
The study concluded that oral imatinib at 200mg daily is well-tolerated as add-on therapy for pulmonary arterial hypertension, with persistent hemodynamic improvements even after treatment cessation.
Read more at this link on the NIH Library of Medicine
Citation
Rothman AMK, Villar S, Middleton J, Roussakis AA, Varian F, Zafar H, Law M, Apperley J, Bartelink IH, Said MM, Delgado-SanMartin JA, Kiely DG, Howard L, Toshner M, Wort SJ, Wilkins MR. Positioning Imatinib for Pulmonary Arterial Hypertension: A Dose Finding Phase 2 Study. Am J Respir Crit Care Med. 2025 Mar 13. doi: 10.1164/rccm.202410-1929OC. Epub ahead of print. PMID: 40080796.