Uptravi Can Help PAH Patients at Moderate, High Risk of Death, Registry Data Show

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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More than three-quarters (76%) of adults with pulmonary arterial hypertension (PAH) being treated with Uptravi (selexipag) either saw no increase or a decline in their risk of death over one year, a study based real-world data reports.

These findings — in nearly 500 people taking part in an ongoing registry, with most determined at entry to have an intermediate or high one-year mortality risk — underscore the importance of risk assessments in determining treatment goals for PAH patients, its researchers said.

Their study, “Patient and disease characteristics of the first 500 patients with pulmonary arterial hypertension treated with selexipag in real-world settings from SPHERE,” was published in the Journal of Heart and Lung Transplantation.

SPHERE (NCT03278002) is an ongoing U.S.-based, real-world registry collecting data from a representative range of adults actively being treated with Uptravi, a medication approved to delay disease progression and reduce the risk of hospitalization in patients with PAH. Uptravi is marketed by Actelion, part of the Johnson & Johnson family of companies.

Data reported covered the first 500 patients who enrolled in SPHERE, all between November 2016 and April 2018.

“Within the PAH treatment paradigm, real-world evidence has become valuable information for physicians to consider when it comes to elevating the standard of care,” Nick Kim, MD, professor of medicine at the University of California San Diego and the study’s first author, said in a press release.

“Findings from the SPHERE analysis reinforce the need for physicians to be conducting routine comprehensive risk assessments and utilizing available tools such as risk calculators to ensure that PAH patients are achieving their treatment goals,” added Kim, who also director of the Pulmonary Vascular Medicine Program at the university.

According to the team, complete patient assessment and risk stratification are essential to guide decisions on — and monitor the response to — treatment.

In the study, researchers assessed the risk for one-year mortality using two different methods: the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk calculators. Then, according to risk scores attained, patients were classified as having a low, intermediate, or high risk for mortality over one year.

SPHERE enrolled both patients newly starting on Uptravi (60 or fewer days prior to enrollment) and those using the treatment for a longer time and with a documented titration regimen.

Most patients (72.4%) were longer-term Uptravi users (more than 60 days before enrollment), and almost all (96.0%) were being treated with at least one PAH-specific medication.

Despite most of these people receiving PAH-specific treatment when they were started with Uptravi, a majority — 67.2% — were determined to be at intermediate risk, and 9.6% at high risk, for one-year mortality.

Indeed, “treatment guidelines recommend a combination therapy in patients not at low risk,” the researchers wrote.

Of these 500 patients for whom data were reported, 77.6% completed the planned 18 months of follow-up.

At the end of the follow-up period, 19.2% had a lower REVEAL 2.0 risk score, 57.8% had no change in their score, and 20.2% had a higher REVEAL 2.0 risk score.

These findings were consistent with COMPERA risk calculations: 21.4% had a lower risk, 54.4% remained stable, and 19.4% saw their risk worsen.

“Risk scores remained stable in [approximately] 55% of patients and improved in [about] 20% at the end of the study,” the researchers wrote.

The team also gathered important information about adjusting the dose of Uptravi during treatment: the median maintenance dose was 1,200 micrograms (ranging from 800 to 1,600 micrograms) twice a day, and 87.8% of patients required more than seven days to increase the dose in increments of 200 micrograms twice daily.

“Thus, patients are titrated more slowly in the real-world settings than the 200-[microgram] twice a day dose per week” used in clinical trials and described in the therapy’s Food and Drug Administration‒approved label, the researchers noted.

At least one adverse event was reported in 72.2% of patients, and 37.6% had a serious side effect. No unexpected adverse effects were observed.

The proportion of patients who stopped taking Uptravi due to treatment-related side effects was 7.2%. The most common adverse events leading to discontinuation were headache (6.5%) and diarrhea (5.1%) in patients newly initiated on Uptravi, and worsening PAH (3.3%) and right ventricular failure (1.9%) in those using it longer term.

“Additional analyses of SPHERE data will provide further insights and valuable information about the clinical characteristics, dosing regimens, and clinical outcomes for patients receiving selexipag [Uptravi] in routine clinical practice,” the researchers wrote.

Added Siân Walker, head of Medical Affairs, Pulmonary Hypertension at Janssen U.S.: “We’re proud to support SPHERE, as data from this registry furthers our understanding of Uptravi within a clinical setting in the U.S. These findings add to the growing body of evidence that demonstrates the need for utilizing risk assessment tools in clinical practice that may optimize the standard of care for patients with PAH.”

Janssen is also part of the Johnson & Johnson group of pharmaceutical companies.

Two of the nine researchers with this study are employees of Actelion, which is sponsoring the SPHERE registry.

A Conversation With Rare Disease Advocates