Selexipag improves outcomes in connective tissue disease-associated PAH in real-world setting

Patients with connective tissue disease-associated pulmonary arterial hypertension benefit from selexipag treatment in the real-world setting, according to new data from the SPHERE analysis.

Kelly M. Chin, MD, assistant professor of internal medicine and director of the pulmonary hypertension program at UT Southwestern Medical Center, Dallas, and colleagues reported data from the first 500 patients (aged 18 years) enrolled in SPHERE, a U.S.-based observational registry of patients with PAH treated with selexipag (Uptravi, Actelion) in real-world settings. Patients treated with selexipag as a new initiation treatment ( 60 days before enrollment) or as previously initiated treatment (> 60 days before enrollment) were included in the analysis and followed up for 18 months. The data cutoff was December 2019.

Twenty-six percent of patients had connective tissue disease-associated PAH (CTD-PAH), 49% had idiopathic PAH and 24% had other diagnoses. For those with CTD-PAH, median time from diagnosis to selexipag treatment initiation was 3.3 years; 31% of patients were new initiators of selexipag.

While baseline demographics and disease characteristics were comparable, patients with CTD-PAH were more likely to be women, Black and have a lower BMI. Patients with CTD-PAH had worse New York Heart Association/WHO functional class, 6-minute walk distance, brain-type natriuretic peptide (BNP) and NT-proBNP compared with those with idiopathic PAH. Patients with CTD-PAH had lower median pulmonary artery pressure, mean right atrial pressure and pulmonary vascular resistance, according to the results.

The total duration of selexipag treatment was 20.6 months among patients with CTD-PAH and 21.5 months among patients with idiopathic PAH. For those with selexipag as newly initiated treatment, median selexipag treatment duration was 16.4 months for patients with CTD-PAH and 16.9 months for patients with idiopathic PAH. Median maintenance dose (1,200 g) and time to maintenance dose (8.3 weeks) were similar among both groups, according to the results.

At selexipag initiation, rates of obesity were lower and rates of concomitant interstitial lung disease, gastroesophageal reflux disease and immune system disorders were higher in patients with CTD-PAH compared with idiopathic PAH, according to the results.

At treatment initiation, most patients with CTD-PAH were receiving dual therapy for PAH. For non-PAH medications, more idiopathic PAH patients were receiving warfarin (15.9% vs. 6.1%) and more patients with CTD-PAH were receiving medications for acid-related disorders (47% vs. 28%), immunosuppressants (32.6% vs. 4.1%) and calcium channel blockers (18.2% vs. 11.4%).

Treatment discontinuation due to adverse events unrelated to PAH progression was reported in 10.6% of patients with CTD-PAH and 9.8% with idiopathic PAH. Discontinuation due to adverse events related to PAH progression was higher in patients with CTD-PAH (15.2% vs. 11%), according to the results.

According to the REVEAL 2.0 risk score calculator, at selexipag initiation, patients with CTD-PAH had a higher mortality risk compared with those with idiopathic PAH. After 12 months, risk status was maintained in the majority of patients after selexipag treatment, according to the results.

The estimated survival probability was lower among patients with CTD-PAH (81.9%) than in those with idiopathic PAH (87.2%). The researchers noted this difference was driven by higher risk at baseline in the patients with CTD-PAH.

“Compared with the baseline, the majority of patients in SPHERE either improved or maintained risk status with treatment,” Chin said during a virtual presentation of the results during the CHEST Annual Meeting. “As expected, patients with CTD-PAH had a lower survival rate after 1 year than those with idiopathic PAH.”

The current analysis is limited by its observational nature and focus on the first 500 patients enrolled in the cohort, according to the researchers.

Reference:

Chin KM, et al. Chest. 2020;doi:10.1016/j.chest.2020.08.1875.