People with PAH-CTD also tolerate the therapy fairly well, according to the study. The PAH part of PAH-CTD refers to high blood pressure in the lungs’ arteries.
The follow-up analysis, “Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension,” was published in the European Respiratory Journal.
PAH can develop as a complication of CTD, which encompasses a range of diseases, including systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Patients with PAH-CTD tend to have a worse disease outcome than patients with idiopathic PAH (IPAH). In addition, some patients with CTD respond to PAH therapy and others don’t.
Uptravi is a selective IP prostacyclin receptor agonist. It inhibits the prostacyclin receptor, leading to widening of narrowed blood vessels, a decrease in blood pressure, and improved pulmonary blood circulation.
The Phase 3 GRIPHON trial (NCT01106014) was a global, double-blind, randomized study to determine PAH-CTD and IPAH patients’ response to Uptravi. It found that treatment decreased by 40 percent the risk of all PAH patients’ disease worsening or of them dying. In PAH-CTD patients specifically, treatment decreased the risk of mortality or morbidity by 41 percent. Disease worsening, or morbidity, was defined as the need for hospitalization, a lung transplant, or poorer six-minute walk test results from the study’s start, among other measures.
After the initial results, researchers decided to do a more detailed analysis of the PAH-CTD patients in the GRIPHON trial. It looked at Uptravi’s effectiveness, how patients did on various doses of the therapy, and their ability to tolerate the treatment.
There were 334 patients with PAH-CTD in the GRIPHON trial — 170 PAH-SSc patients, 82 PAH-SLE patients, and 82 patients with CTD or a mix of CTD and other conditions.
The CTD group in the GRIPHON population was older than the overall population. It also had a greater proportion of women and patients who had been diagnosed relatively recently.
PAH-SSc patients tended to be more impaired at the start of treatment, and their disease progressed faster. PAH-SLE patients tended to be less impaired at thestart and their disease course slower.
PAH-CTD tolerated different doses of Uptavi as well as the overall GRIPHON population.
Uptravi decreased the risk of death or disease worsening in PAH-CTD patients by 41 percent, compared with a placebo. The risk reduction was 44 percent in PAH-SSc patients, and 34 percent in PAH-SLE patients, indicating a more beneficial effect for PAH-SSc patients.
Another measure that the study analyzed was the treatment’s effect on patients’ six-minute walk distance, a test of exercise capacity. Results were similar between PAH-CTD patients and the overall GRIPHON population.
PAH-SSc patients in the placebo group — that is, those not receiving Uptravi — experienced a greater deterioration in exercise capacity. Musculoskeletal problems are a hallmark of SSc.
Uptravi improved PAH-SLE patients’ six-minute walk results, while placebo had no impact on their performance.
Adverse events involved known side effects of selexipag treatment.
Researchers concluded that PAH-SSc and PAH-SLE patients can tolerate Uptravi well. This they considered an important point, as “patients with PAH-CTD often have a high symptom burden due to comorbid musculoskeletal and gastrointestinal involvement and … [we may] expect poorer tolerability … compared with other PAH patients,” they wrote. “However, selexipag tolerability in patients with PAH-CTD was generally consistent with that in the overall GRIPHON population” with only a slightly higher number of these patients stopping treatment due to adverse events (19.2%) than overall (14.3%).
Based on the lower morbidity and mortality rates among treated patients, the study recommended Uptravi treatment with dosing based on a PAH-CTD patient’s personal tolerance.