Failure to tolerate continuous subcutaneous treprostinil in pediatric pulmonary hypertension patients.

Continuous subcutaneous (SubQ) treprostinil is an effective therapy for pediatric patients diagnosed with pulmonary hypertension (PH). To date, the clinical characteristics and factors associated with failure to tolerate this therapy have not been described. The purpose was to describe patient-reported factors contributing to SubQ treprostinil intolerance in pediatric patients with PH. A retrospective descriptive study was performed at 11 participating sites in the United States and Canada for patients younger than 21 years of age diagnosed with PH who failed treatment to tolerate SubQ treprostinil between January 1, 2009, and December 31, 2019. All data were summarized using descriptive statistics. Forty-one patients met the inclusion criteria. The average age at SQ treprostinil initiation, and length of treatment, was 8.6 years and 22.6 months, respectively. The average maximum dose, concentration, and rate were 95.8 ng/kg/min, 6.06 mg/mL, and 0.040 mL/h, respectively. The reasons for failure to tolerate SubQ treprostinil included intractable site pain (73.2%), frequent site changes (56.1%), severe site reactions (53.7%), infections (26.8%), and noncompliance/depression/anxiety (17.1%). Thirty-nine (95.1%) patients transitioned to a prostacyclin therapy with 23 patients transitioning to intravenous prostacyclin, 5 to inhaled prostacyclin, 5 to oral prostacyclin, and 7 to a prostacyclin receptor agonist. A subset of pediatric PH patients failed to tolerate SubQ treprostinil infusions despite advances in SubQ site maintenance and pain management strategies. Intractable site pain, frequent SubQ site changes, and severe localized skin reactions were the most common reasons for failure.

Factors determining change in treatment for ambulatory children with pulmonary arterial hypertension: Implications for monitoring.

While care models adapt to the COVID-19 pandemic with virtual and hybrid visits, clinical factors associated with treatment changes among ambulatory pediatric pulmonary arterial hypertension (PAH) patients are not well characterized. To understand which data critically altered treatment recommendations, we conducted a retrospective review among ambulatory children with Group 1 PAH to determine optimal visit and diagnostic strategies. Changes in management included: unplanned new treatments, dose modifications of vasodilators or diuretics, unscheduled hospitalizations, or changes to activity recommendations, catheterization schedule, or other testing. Factors prompting management changes were classified as symptoms, exam findings, or diagnostic tests. Across 398 ambulatory visits by 48 patients, 38 patients (79%) at 88 visits (22%) required change in management, most commonly in targeted PH medication. Changes were driven by symptoms alone (15%), diagnostic testing alone (47%), exam only (2%), symptoms and exam (2%), combination of testing and symptoms or testing and exam (25%), and other reasons (9%). Patients with World Health Organization functional Class IV (odds ratio [OR] 9.04 vs. Class I, p = 0.014) or Class III (OR 2.08 vs. Class I, p = 0.050) were more likely to undergo change in management. However, among Class I patients, 18% of visits generated changes in management because of test findings. While multiple factors affect management in ambulatory pediatric PH, neither symptoms nor exam was sufficient for identifying patients warranting clinical change in management. Testing accounted for most changes. Thus, in-person or hybrid surveillance including history, exam, and diagnostic testing remains essential for optimal management of pediatric PAH.