Different Uptravi maintenance doses led to similar outcomes: Study
No impact found on hospitalization risk for adults with PAH in real world
Differences in Uptravi (selexipag) maintenance doses have no impact on the risk of hospitalization among adults with pulmonary arterial hypertension (PAH), a real-world claims analysis suggests.
While different maintenance doses did not affect treatment adherence or discontinuations among U.S. patients in the real world, dose adjustments were more frequent for those who took lower regular doses, the data analysis found.
“The findings in this diverse, real-world population of patients with PAH reinforced an individualized approach to the dosing scheme to maximize benefit-risk and achieve the highest tolerated dose with [Uptravi],” the researchers wrote.
The team called the overall findings “reassuring,” and noted that they “reinforced the consistency in efficacy” of Uptravi maintenance found in other analyses.
The results of the claims analysis were detailed in “Impact of selexipag maintenance dose on persistence, adherence, and hospitalization in US patients with pulmonary arterial hypertension,” a study published in the journal Pulmonary Circulation.
Investigating patient outcomes with varying Uptravi maintenance doses
Uptravi is approved for adults with PAH, a condition marked by high blood pressure caused by the narrowing of blood vessels that transport blood through the lungs. The condition has several known causes, including genetics, connective tissue diseases such as scleroderma and lupus, heart abnormalities, viral infections, and chronic liver disease.
The medicine is designed to mimic the action of prostacyclin, a naturally occurring molecule found in the body that relaxes and widens blood vessels. It’s intended to lower blood pressure, ease symptoms, slow disease progression, and reduce the risk of PAH-related hospitalization.
The recommended starting Uptravi dose is 200 micrograms (mcg), taken twice daily. It can be increased, or titrated, weekly to the highest tolerated individualized maintenance dose of up to 1,600 mcg twice daily.
However, the patterns of Uptravi maintenance doses and whether these varying dosing regimens are associated with differences in PAH patient outcomes in real-world settings are unclear.
To address this knowledge gap, a scientist at the Mayo Clinic in Florida, along with researchers from Janssen Scientific Affairs in New Jersey, analyzed data from the Komodo claims database. That database holds medical and prescription claims from patients with insurance coverage, including commercial, Medicaid, and Medicare Advantage. The study was funded by Janssen, the company that markets Uptravi, and Actelion Pharmaceuticals.
Data was culled for more than 1,100 people with PAH in the U.S. Overall, the analysis covered 634 patients (53.5%) who completed the titration phase and reached their twice-daily individualized maintenance dose. Nearly three-quarters of these individuals — 459 or 72.4% — were women.
Among these patients, 167 (26.3%) received a low maintenance dose (200-400 mcg), 189 (29.8%) a medium dose (600-1,000 mcg), and 278 (43.8%) reached a high dose (1,200-1,600 mcg).
Demographic characteristics, such as age, sex, U.S. region, and healthcare plan type, were generally similar across the different dose groups.
Connective tissue disease was the most identifiable common cause of PAH, seen in 18.6% of patients, followed by portal hypertension, or high blood pressure in the major vein that leads to the liver, which was noted for 9% of patients. HIV infection was the cause of PAH for 3.8%, and congenital heart defect was cited for 3.5%.
Shortness of breath was the most prominent PAH symptom among these participants (44%) before receiving a Uptravi maintenance dose, and it was more common in the high dose (48.2%) than in the lower dose groups. Other pre-maintenance symptoms included chest pain, affecting about 31% of patients, swelling in the lower legs or hands, seen in approximately 22%, and fainting, seen for about 11%.
The occurrence of co-existing medical conditions before Uptravi maintenance, including heart attack, congestive heart failure, chronic obstructive lung disease (COPD), obesity, and diabetes, was similar across dose groups.
The pattern of PAH therapies and regimens before Uptravi maintenance was also similar in the different dose groups. The exception was other prostacyclin mimics, with more patients in the high-dose group previously receiving these medications than in the lower-dose groups.
Risk of hospitalization similar for all patients over 5 years
Over time, more high-dose patients remained on the initial Uptravi dose with fewer dose adjustments relative to low- and medium-dose patients. In particular, maintenance dose adjustments occurred in 72.5% of patients in the low-dose group, 61.9% in the medium-dose group, and 34.5% in the high-dose group.
The maintenance dose was boosted by 200 mcg or more at least once in 67.1% of low-dose patients, 48.1% of medium-dose patients, and 27% of those on a high dose. Conversely, the maintenance dose was reduced in 55.7% of patients taking a low dose, 41.8% taking a medium dose, and 20.9% of those receiving a high dose.
“These results suggest that [Uptravi] dose adjustments were implemented frequently in the patients in the low and medium [dose groups], but that the higher doses were not sustained in many patients,” the researchers wrote.
Across all groups, no significant differences were noted in adherence to Uptravi, defined as the proportion of days covered by 80% or more, with patients permitted an off-treatment period of up to 45 days. Similar findings were seen for treatment discontinuations.
Treatment persistence and hospitalization outcomes … were similar irrespective of [dose] group.
Finally, the risk of first all-cause hospitalization and first PAH-related hospitalization was similar for patients during the follow-up period of five years regardless of the maintenance dose.
“Treatment persistence and hospitalization outcomes … were similar irrespective of [dose] group,” the researchers concluded. “Future studies should evaluate the same outcomes within other databases (e.g., claims, electronic health records, Medicare) with greater study power.”
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