Upfront Combination Therapy May Improve Outcomes in Pediatric PAH: Study
Data from the TOPP-2 registry showed wide variation in initial treatment strategies for pediatric pulmonary arterial hypertension (PAH). Patients whose therapy was escalated during the first year—from single to dual therapy in lower-risk patients or to TripleX therapy in higher-risk patients—had worse outcomes than those who received more intensive combination therapy from the outset. These findings support upfront combination therapy rather than sequential treatment escalation in children with PAH.
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.
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.
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.
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.
Reference:
Frank, Benjamin S., et al. "Improved Outcomes With Early Aggressive Therapy in Pediatric Pulmonary Hypertension." The European Respiratory Journal, 2026.
Keywords:
Upfront, Combination, Therapy, Improve, Outcomes, Pediatric, PAH, Study, Frank, Benjamin S
