Benjamin S. Frank, Maurice Beghetti, Rolf M. F. Berger, Damien Bonnet, Tilman Humpl, Julie Wacker, Johannes M. Douwes, Julien Grynblat, Paul J. Critser, David Bowers, D. Dunbar Ivy, on behalf of the TOPP-2 Investigators
University of Colorado. Geneva University Hospitals and Faculty of Medicine and University of Geneva. Beatrix Children’s Hospital, University Medical Center Groningen and University of Groningen. Hopital Universitaire Necker-Enfants Malades and Universite de Paris Cite. District Hospital of Loerrach. University of Cincinnati College of Medicine. University of Suffolk.
United States, Switzerland, Netherlands, France, Germany and United Kingdom
European Respiratory Journal
Eur Respir J 2026;
DOI: 10.1183/13993003.00327-2026
Abstract
Background: Pediatric pulmonary arterial hypertension (PAH) carries high mortality with 81% 5-year transplant-free survival. The global Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension-2 (TOPP-2; NCT02610660) registry was created to assess the treatments and outcomes of newly diagnosed pediatric PAH patients. This study evaluates real-world treatment strategies and their relationship with outcomes.
Methods: Within TOPP-2, 445 subjects with newly diagnosed, catheterization-confirmed WSPH Group 1 pediatric PAH were enrolled. Treatment regimens were classified as none, calcium channel blocker monotherapy, PAH-targeted Monotherapy (Mono), Dual, Triple (enteral/inhaled only), or triple including parenteral prostanoid (TripleX). Baseline treatment strategy was defined as medications received three months following diagnosis. Primary clinical endpoint was death or lung transplantation.
Results: Dual therapy was the most common baseline treatment regimen (40.2%), followed by Monotherapy (29.0%). Phosphodiesterase type 5 inhibitors were the most common class of PAH-targeted therapy (72.4%) followed by endothelin receptor antagonists (59.3%). Adjusting for disease severity at diagnosis, baseline Dual patients had lesser hazard of death/transplant than Mono patients escalating to Dual by year one (HR=0.30, 95% CI=0.16-0.56, p<0.001). Baseline TripleX patients had lesser hazard of death/transplant than those started on enteral/inhaled therapy only and escalated to parenteral by year one (HR=0.28, 95% CI=0.15-0.50, p<0.001).
Discussion: A wide range of pediatric PAH initial medication strategies were observed in the TOPP-2 registry. Therapy regimen escalation within the first year, to Dual for lower-risk patients or to TripleX for higher-risk patients, was associated with worse outcomes compared to those treated more aggressively upfront, supporting upfront over sequential combination therapies.
Category
Medical Therapy. Efficacy or Lack of Efficacy
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes