Selexipag (Uptravi) does not change the level of daily activity of patients with pulmonary arterial hypertension (PAH), results from the phase 4 TRACE trial suggest.
"We had no preconceived idea if this drug would improve exercise capacity," said Luke Howard, MD, from Imperial College Healthcare NHS Trust in London. It was clear, however, that 6-minute walk tests conducted a few times a year "don't paint a picture of what daily life is like for patients on selexipag."
The oral prostacyclin IP receptor agonist is prescribed to slow the progression of PAH and reduce hospital admissions, but there are no studies that show whether it improves quality of life.
Howard and his team turned to wearable technology to "capture a snapshot of everyday life," he explained during his presentation at CHEST 2020.
The primary concern of the investigators was to get TRACE participants — all with PAH — to wear a wrist device; they did not encourage patients to become more active. "We wanted a true picture of the impact of the drug itself," he noted.
After 24 months of daily tracking, "there was no benefit to increased daily activity for patients taking this drug," Howard told Medscape Medical News. "That was a bit deflating."
The daily activity of TRACE participants was "slightly more elevated" in the selexipag group than in the placebo group. "We saw some numerical drops in activity in the placebo group, and a trend that might make a difference over a longer, bigger study, but not in a statically significant way," he reported.
In the randomized, blinded trial — the first to track the activity of PAH patients — 53 participants received selexipag and 55 received placebo. All 108 wore a wrist accelerometer (GT9X Link) that counted the number of steps taken each day, providing an indication of daily activity.
Device compliance — the mean number of days in which the device was worn for at least 7 hours during a 14-day predrug period — was similar in the selexipag and placebo groups (13.2 vs 13.0 days).
|Baseline Characteristics of the TRACE Participants|
|Measure||Selexipag Group||Placebo Group|
|Median time from diagnosis, months||38||34|
|Mean 6-minute walk distance, m||453.1||449.5|
|WHO class II PAH, %||62.3||74.5|
"We wanted to make sure we had people who were stable and weren't enrolled in a rehabilitation program; we didn't want any competing influences," Howard explained. All in all, the participants were in pretty good shape. "There was a low risk of a bad outcome."
The primary end point was change in activity from baseline to week 24. The secondary end points were PAH-SYMPACT health quality-of-life tests and 6-minute walk distance.
Similar Activity Levels in Both Groups
|Change in Activity From Baseline to Week 24|
|Activity||Selexipag Group||Placebo Group|
|Nonsedentary activity, min||–0.7||–15.0|
|6-minute walk distance, m||18.3||9.8|
As expected in a population in which the majority of patients meet the criteria for WHO FC II PAH, all participants had low PAH-SYMPACT domain scores throughout the trial.
All adverse events were "consistent with the known profile" of selexipag, and there were no deaths, Howard reported.
"We did not show any significant benefit to taking the drug;" however, the drug is marketed for the prevention of disease progression, and this finding "doesn't change that," he said.
"Pulmonary rehabilitation is one of the most vital management issues with chronic lung disease," Riddhi Upadhyay, MD, from the Carle Foundation Hospital in Urbana, Illinois, said during her CHEST 2020 presentation on improving PAH rehabilitation referral rates.
"We know it improves exercise capacity, lung function, and decreases total hospital stays and recurrent hospital admission," she explained. And studies have shown that PAH rehabilitation "also reduces frailty and improves quality of life.”
In their study, Upadhyay and her colleagues showed that when pulmonary rehabilitation is added to the discharge order set, referrals increase by 60%.
They attribute their success to "recognizing the benefits of pulmonary rehab and understanding where interventions are required."
An encouraging takeaway from the TRACE data is that it established that daily activity can be tracked in this patient population. "We think we might need to encourage these patients to get active, maybe combine the drug with a formal rehabilitation program; that might increase motivation," Howard said.
"People don't necessarily do more just because they can," he noted.
Howard has received consulting fees from Actelion.
CHEST 2020: American College of Chest Physicians Annual Meeting. Presented October 18, 2020.
Medscape Medical News © 2020
Cite this: Selexipag Has No Effect on Daily Activity in PAH Patients - Medscape - Oct 20, 2020.