DENVER – Inhaled treprostinil was well tolerated and was associated with improvements in exercise capacity and functional class when added to background therapy in a retrospective study of 18 children with pulmonary arterial hypertension.
Inhaled treprostinil (iTRE; brand name, Tyvaso) was approved in 2009 for the treatment of patients with group 1 pulmonary arterial hypertension (PAH) as add-on therapy to improve exercise ability. It was primarily studied in adults with New York Heart Association class III symptoms, and has not been previously studied in children with PAH, said Dr. Erika B. Rosenzweig, director of the pulmonary hypertension center at Columbia University Medical Center in New York.
Dr. Erika B. Rosenzweig
This study included 6 girls and 12 boys with PAH who were seen at either the Columbia center or the Children’s Hospital in Aurora, Colo., between September 2009 and January 2011. They had a mean age of 11 years, a mean weight of 42 kg, and a mean body mass index of 19.4 kg/m2. A total of 11 patients had idiopathic PAH and 7 had associated PAH, including 5 with congenital heart defects. All were on background therapy at the time of iTRE initiation, with the majority (11) on combined endothelin receptor antagonist and phosphodiesterase-5 inhibitor therapy. Prostanoid therapy had been given previously to 10 patients.
All patients received three to nine breaths, with 6 mcg per breath of iTRE, four times daily. The mean treatment duration was 11.5 months (range, 2-20 months). Nine patients received nine breaths four times a day, whereas five patients did not reach that maximal dose because of side effects or per physician discretion. Four patients discontinued iTRE, including three because of bronchospasm, and one because of noncompliance with all medications (who died 3 months later). Side effects requiring down-titration included cough in one patient and nausea/emesis in two. Milder side effects that did not require a dose change occurred in two to six patients each, including cough, sore throat, dyspnea, wheezing, flushing, headache, and diarrhea. No child discontinued because of inability to self-administer the medication, Dr. Rosenzweig noted at an international conference of the American Thoracic Society.
At baseline, two patients were in World Health Organization functional class I, seven were class II, eight in class III, and one in class IV. At follow-up, there were 7 in class I, 10 in class II, 1 in class III, and none in class IV. In all, functional class improvements were seen in 11 of the 18 children.
Of the seven children who were able to complete the 6-minute walk test, the mean improvement was from 446 to 472 meters, which was statistically significant. Of four who completed cardiopulmonary exercise testing, the mean workload improved from 59 to 74 watts and mean peak oxygen consumption from 20 to 22 mL/kg per minute. Neither of those findings was statistically significant. However, in 10 of the patients with measurements of brain natriuretic peptide (which reflects right ventricular dysfunction), levels dropped significantly, from a mean of 88 to 66 pg/mL.
"The authors recognize the limitations of the small sample size, but based on these early data in children, we believe that further study of iTRE appears warranted in larger cohorts of pediatric patients," she concluded.
Dr. Rosenzweig disclosed that she has received research support from and has served as a consultant for United Therapeutics, the manufacturer of Tyvaso.