Mental Health Comorbidities Affect Uptravi Prescribing for PAH

A number of different factors, including cost, patient education, and side effects, can affect the likelihood that an individual patient adheres to a prescribed medication regimen. However, in diseases like pulmonary arterial hypertension (PAH), adherence is particularly important because of the high risk of mortality if patients are left untreated.

Among the factors that can affect treatment patterns and outcomes is comorbidities, and much has been written about how physical comorbidities affect people with PAH. Yet, Sean Studer, M.D., and Michelle Han, Pharm.D., told Managed Healthcare Executive mental health comorbidities have received relatively little attention in PAH.

“A patient’s health is a comprehensive picture of their mental and physical wellbeing,” they wrote, in an email. “There was a gap in treatment knowledge for this patient population, which drove us to dig deeper into treatment patterns for patients with PAH.”

Han, associate director for U.S. medical affairs and therapeutic area lead for pulmonary hypertension at Johnson & Johnson Innovative Medicines, was a co-author of a new report on mental health comorbidities and PAH that was presented at the American College of Chest Physicians’ 2024 annual meeting, in Boston. She and Studer, the company’s vice president of medical affairs, discussed the results with Managed Healthcare Executive. They said mental health comorbidities are meaningful not only because of how they might affect patients’ medication adherence, but also because of how they affect physicians’ approaches toward patients.

“It is a general perception that patients with mental health illness are often at higher risk for nonadherence,” they wrote. “As such, clinicians may be cautious in prescribing medications that require monitoring and patient engagement in management.”

The study used registry data to analyze prescription drug prescribing and use patterns among 759 adults with World Health Organization Group 1 PAH who were prescribed the prostacyclin-receptor agonist Uptravi (selexipag). Of those adults, approximately 1 in 3 (246, or 32%) reported mental health comorbidities, including depression, anxiety or anxiety disorder, or bipolar disorder. All but one of those patients reported receiving medication to treat their mental health disorder. The study was named Selexipag: The Users Drug Registry, or SPHERE for short.

The investigators found that it took longer for physicians to prescribe Uptravi in patients with mental health comorbidities. For those without mental health comorbidities, it took 2.6 years from initial diagnosis to selexipag initiation; for those with mental health comorbidities, the span was 3.3 years.

Studer and Han noted that Uptravi’s titration period requires regular patient-provider engagement, which they said may have led to clinicians holding back on starting a prescription. They said it might also be due to a choice to focus on mental health issues first, “which might result in less aggressive initial treatment for PAH.”

The data also showed that patients with mental health comorbidities were prescribed dual endothelin receptor antagonist–phosphodiesterase-5 inhibitor therapy at lower rates (34% versus 45%) compared with those without mental health comorbidities. Studer and Han said the trial design did not allow them to capture the clinical rationale behind the lower prescribing rate, but they said it might be due to a desire to lessen therapeutic complexity.

“Patients with mental health comorbidities may be prescribed medications for additional conditions beyond PAH,” they noted. “These can lead to complex medication regimens, so it might be difficult for them to add a medication (or two).”

Despite possible concerns about regimen complexity, the investigators found that treatment persistence — the time patients continued taking a medication — was similar in both groups, and that median duration of Uptavi titration and median individualized doses were similar in both groups.

The takeaway, Studer and Han said, is that this real-world evidence suggests people with PAH and mental health comorbidities “can be treated as actively as patients without these comorbidities.”

Although caution might be an understandable approach in patients with mental health comorbidities, Studer and Han said the latest data — including findings presented at the recent World Symposium on Pulmonary Hypertension (WSPH) — support a more proactive approach.

“[I]t is imperative patients are optimized on therapy as soon as possible,” Studer and Han wrote. “The recent WSPH emphasized the importance of the first year of treatment after PAH diagnosis and recommended a first follow-up risk assessment at 3-4 months and early treatment escalation.”