Uptravi Delays Progression of PAH Associated with Lupus and Other Connective Tissue Diseases, Trial Shows

Uptravi (selexipag) delays the progression of pulmonary arterial hypertension in people with PAH that is associated with connective tissue diseases, including lupus, a Phase 3 clinical trial shows.

Patients also tolerate Uptravi well, researchers said. PAH associated with connective tissue disease is also known as PAH-CTD, and PAH associated with lupus as PAH-SLE.

The study, “Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension,” was published in the European Respiratory Journal.

Uptravi, made by Actelion, is an approved treatment for PAH. The prostacyclin receptor agonist works by activating the prostacyclin receptor, which widens blood vessels. The widening reduces blood pressure and improves pulmonary circulation.

PAH can arise as a complication of CTD, which includes multiple diseases such as systemic sclerosis (SSc) and lupus. Studies have shown that patients with PAH-CTD have worse outcomes than patients with idiopathic PAH — or PAH that stems from an unknown cause. That’s because the underlying cause of PAH-CTD can interfere with treatment response and outcome.

Actelion conducted the GRIPHON clinical trial (NCT01106014) to see how patients with either PAH-CTD or idiopathic PAH would respond to Uptravi.

The trial covered 334 patients with PAH-CTD. One hundred seventy had PAH-SSc, 82 PAH-SLE, and 82 another kind of CTD or a mixed form. It was the largest population of patients with PAH-CTD ever studied.

The demographics of the PAH-CTD patients were different from the rest of the GRIPHON population. The CTD subgroup was slightly older, with a higher ratio of women and a shorter time since diagnosis.

Among the CTD subtypes, PAH-SSc patients were more impaired at the start of the study and experienced a more progressive disease course, while PAH-SLE patients were less impaired and experienced a slower disease course.

Uptravi decreased by 41 percent the risk of PAH-CTD patients having their disease worsen or dying, compared with a placebo, researchers said. The improvement was not associated with the kind of PAH therapy that patients were taking before the trial started, or the subtype of CTD.

There was no difference between the proportions of all GRIPHON patients in the low-dose, medium-dose, or high-dose groups and the proportions of the PAH-CTD patients in each of the groups. This indicated that  PAH-CTD patients tolerated each dose as well as the overall population did.

Another factor the study analyzed was Uptravi’s effect on the distance patients could walk in six minutes. It was similar between patients with PAH-CTD and the overall GRIPHON population.

Among CTD subgroups, PAH-SSc patients in the placebo group experienced greater deterioration because musculoskeletal development is a key part of the pathogenesis of SSc. Uptravi improved the musculoskeletal performance of people with PAH-SLE, while the performance of those on a placebo remained the same. This was an important finding because little data is available on PAH-SLE patients.

Adverse events in the study were related to the prostacyclin pathway and were known side effects of Uptravi treatment.

“In our study, selexipag treatment was well tolerated and delayed the progression of PAH irrespective of CTD subtype and baseline PAH therapy. These data support the use of multiple PAH therapies when treating patients with PAH-CTD and emphasise that this treatment strategy can yield benefits in a population who had previously been considered difficult to treat,” the authors concluded.