Real-World Data Show Safety, Efficacy of Opsumit for PAH Due to Scleroderma

Alice Melão, MSc avatar

by Alice Melão, MSc |

Share this article:

Share article via email
C21 trial

Real-world clinical data support the use of Opsumit (macitentan) to treat people with pulmonary arterial hypertension (PAH) due to scleroderma (PAH-SSc).

The findings revealed similar safety results and comparable therapeutic efficacy in people with PAH-SSc as seen in patients with idiopathic or hereditary PAH — the indications for which the oral medicine is approved.

“Treatment with [Opsumit] in this high-risk group of patients with [PAH-SSc] had similar outcomes compared with patients with idiopathic PAH,” Victor Test, MD, co-chair of the CHEST scientific program committee and professor at Texas Tech University Health Sciences Center, said in a press release. “This result is encouraging for this high-risk group in a real-world setting.”

The findings were discussed at the CHEST Annual Meeting 2019, held Oct. 19-23 in New Orleans, La., in a presentation titled “Macitentan in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease: Real-World Evidence from the Combined OPUS/OrPHeUS Data Sets.”

Typically, people who have PAH associated with a connective tissue disease (CTD) such as scleroderma have a worse prognosis than those with other forms of PAH.

Actelion Pharmaceuticals‘ Opsumit is an oral therapy approved in the U.S. and Europe to lessen symptoms and progression of PAH, but not when associated with scleroderma. It works by blocking endothelin receptors, which results in less contraction and narrowing of blood vessels. That, in turn, can lower the blood vessels’ resistance to blood flow and reduce blood pressure in the lungs.

Researchers now analyzed pooled clinical data collected from two Actelion-sponsored registry studies. Both OPsumit USers (OPUS, NCT02126943, still recruiting in the U.S. and Puerto Rico) and OPsumit Historical USers (OrPHeUS, NCT03197688) provided real-world information on the outcomes of people with PAH newly started on Opsumit — including those with PAH associated with a connective tissue disease.

Overall, the analysis included data from 659 individuals with PAH-SSc, and 2,283 people with idiopathic or hereditary PAH (IPAH/HPAH).

Among PAH-SSc participants, 71.6% showed severe physical impairment, as determined by a functional class of III/IV at treatment initiation. They started taking Opsumit at a median age of 64 years, with 45% of patients starting the treatment six months after PAH diagnosis. Treatment with Opsumit lasted for a median of 14.7 months in PAH-SSc patients and for 13.2 months in the IPAH/HPAH group.

Results showed slightly higher hospitalization rates among people with PAH-SSc, with 40.2% experiencing at least one hospitalization during follow-up compared with 36.3% in the IPAH/HPAH group. Still, safety results were similar in both groups.

A total of 199 (30.2%) PAH-SSc patients and 748 (32.8%) of those with IPAH/HPAH discontinued treatment. Adverse events led to discontinuation in 114 (17.3%) patients with PAH-SSc and 390 (17.1%) with IPAH/HPAH. Meanwhile, 78 (11.8%) people with PAH-SSc and 350 (15.3%) with the other PAH forms stopped treatment for other reasons.

Additional analysis revealed similar proportions of patients alive after one year of Opsumit treatment — 92% of those with PAH-SSc and 93% of the individuals with IPAH/HPAH.

The results also showed comparable proportions of participants with levels of liver enzymes three times above normal, which indicates liver damage. Specifically, 3.9% of those in the PAH-SSc group and 2.7% in the IPAH/HPAH group had those higher liver enzyme levels.

“In this real-world data set, the clinical outcomes and safety profile in patients with PAH-SSc are generally consistent with those of IPAH/HPAH patients,” the researchers said. “These data add to the body of evidence supporting the use of [Opsumit] for the treatment of PAH-SSc.”

Of note, the researchers were employees of Actelion, or received funding from the company, or were consultants or participated in advisory committees.