Uptravi Improves Connective Tissue Disease-Associated PAH, Regardless of Disease Subtype, Trial Shows

Uptravi (selexipag) slows the progression of connective tissue disease associated with pulmonary arterial hypertension, regardless of the type of connective tissue disease, according to a Phase 3 clinical trial in Germany.

The therapy also increases the time it takes for the disease, known as CTD-PAH, to worsen and for patients who have it to die, the trial indicated.

Dr. Marius M. Hoeper of the Hannover Medical School and German Center for Lung Research led the study. The article that the team published about it in the European Respiratory Journal was titled  “Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension.”

Pulmonary arterial hypertension, or PAH, can develop as a serious complication of CTD. Patients with PAH-CTD usually have worse outcomes than those with idiopathic PAH — that is, PAH with no apparent cause.

A PAH-CTD patient’s response to therapy and the outlook for their disease depend on the kind of CTD they have, scientists have believed. But evidence on this has been limited, especially evidence covering the various types of CTD.

Uptravi, marketed by Actelion, is a selective agonist of the prostacyclin receptor, which means it helps the enzyme prostacyclin widen blood vessels in the lungs. Narrowing of those vessels is associated with PAH.

The Phase 3 GRIPHON trial (NCT01106014) evaluated Uptravi’s effectiveness as a PAH treatment. It covered 1,156 patients, 334 with PAH-CTD — the largest patient population ever in a study of this type.

Uptravi led to a 41 percent increase in the time between the start of treatment and the first signs of the disease worsening or the death of a PAH-CTD patient, compared with a placebo. It also slowed the disease’s progression and reduced the number of patients’ hospitalizations, researchers said.

These benefits were in line with the results of studies dealing with other PAH-CTD therapies.

In addition to looking at Uptravi’s effectiveness among PAH-CTD patients as a whole, researchers looked at its ability to help those with two types of CTD: scleroderma and systemic lupus erythematosus, or SLE.

One hundred seventy of the patients had PAH-scleroderma, 82 had PAH-SLE, and an additional 82 had other types or undefined types of CTD.

Thirty-three percent of the general PAH population in the trial were receiving endothelin receptor antagonists or phosphodiesterase type 5 inhibitors when the trial started.

The condition of PAH-scleroderma patients was worse before the trial started and their disease had progressed more than the overall population, researchers said. But the condition of those with PAH-SLE was better at the start than the population as a whole, and their disease had progressed less.

Importantly, the research team found that Uptravi was as effective at treating those with PAH-scleroderma or PAH-SLE as it was at treating the CTD-PAH population as a whole. Any therapy that patients were receiving before they began using Uptravi had no effect on Uptravi’s effectiveness, researchers added.

The team found improvements in a commonly used biomarker of PAH across the CTD population as a whole and in the subtypes. That biomarker is levels of N-terminal prohormone of brain natriuretic peptide, or NT-proBNP.

Patients tolerated Uptravi well, researchers added.

Overall, the results showed that Uptravi benefitted PAH-CTD patients, by itself or in combination with an endothelin receptor antagonist or a phosphodiesterase type 5 inhibitor, the researchers wrote.

The findings “support the use of multiple PAH therapies when treating patients with PAH-CTD and emphasize that this treatment strategy can yield benefits in a population who had previously been considered difficult to treat,” the team concluded.