PAH treatment Opsynvi endorsed by patients, clinicians
Patients like convenience; doctors say single tablet improves adherence
Treatment with Opsynvi (macitentan and tadalafil) as a single-tablet combination therapy for people with pulmonary arterial hypertension (PAH) is highly valued by patients and endorsed by clinicians, according to interviews conducted during the Phase 3 A DUE trial.
All patients interviewed said that a single, once-a-day pill to manage PAH enhanced the convenience of treatment and led to greater treatment adherence.
Clinicians, meanwhile, felt that Opsynvi would be well-received in clinical practice and assist in implementing the guideline-recommended combination treatment of PAH.
The interview study, “Single-Tablet Combination Therapy of Macitentan/Tadalafil for Patients with Pulmonary Arterial Hypertension: Qualitative Interview Study of the A DUE Phase 3 Trial,” was published in Advances in Therapy.
Opsynvi is an oral therapy approved in the U.S. for adults with PAH in World Health Organization functional class 2 or 3. It’s a fixed-dose combination of macitentan and tadalafil, two medicines with different mechanisms of action that relax and widen blood vessels to facilitate better blood flow. Treatment with Opsynvi intends to improve exercise capacity while reducing the risk of clinical worsening and hospitalizations.
PAH treatment can be a burden
Data from the Phase 3 A DUE trial (NCT03904693) supported Opsynvi’s approval, demonstrating that it significantly reduced pulmonary vascular resistance, a measure of resistance to blood flow, compared with either macitentan or tadalafil alone. After the 16-week main trial, some participants entered an open-label treatment period, in which all received Opsynvi for up to two years.
During the open-label phase, researchers asked 26 patients and 18 clinicians to share their experience with the medication, either before the trial or during the double-blind and open-label periods.
Before the trial, all patients spoke about the pill burden, indicating that they were taking between one and 15 pills per day for PAH and co-existing conditions, which made them feel overwhelmed. Patients also mentioned the impact of pill burden on their mental health. Of the 14 patients who previously received a PAH-specific treatment, five said they spontaneously forgot to take it.
“I mean, they’re little pieces of time here and there… it is actually time-consuming,” one patient said.
Another said the regimen was “making me sad, because I was like, ‘they [there] are too many pills and this is progressing fast.”
During the double-blinded portion of the main trial, patients took four pills, containing either the combination therapy with placebos or the individual medicines, each with a placebo against the other medications.
All 26 patients highlighted the need to plan more each week and day to ensure they had all the right pills, taking steps including setting alarms and creating routines. This extra work and planning sometimes affect ed their emotional well-being by increasing stress levels. Still, nearly all patients (24of 26) remembered to take the medicine.
“That was rough,” said a participant. “It took me a little bit to adjust [to taking so many tablets]. I had to put a reminder in my phone.”
Another said, “I’m telling you… I was always stressed out thinking [about all of the pills].”
‘I would honestly be ecstatic’
During the open-label phase, all patients expressed positive thoughts, feelings, and experiences with a single Opsynvi treatment, preferring the single tablet over the multiple tablets. Patients said it was convenient, helped them adhere to the medicine, and positively impacted their day-to-day lives by improving overall management and stress levels. Five patients reported that fewer pills made them feel less “sick.” All patients said they were satisfied with the medication.
“It’s a lot easier [taking one tablet],” a patient said. “And I don’t have to… follow a book, I just… open the bottle and… take one.”
Another said, “I would honestly be ecstatic [to continue taking the single tablet]… a lot easier to fit just one pill for something, into my rotation or my schedule.”
When the 18 clinicians were asked to discuss their typical approaches to treating PAH, 10 said they started patients on combination therapy. The others said they typically started patients on single treatment with a quick progression to combination therapy. Clinicians said their patients usually take between five and 14 pills for PAH and other co-existing conditions.
‘We start with combination treatment… almost in all of the patients… that present in functional class 2, 3,” a clinician said.
All 18 clinicians spoke positively about a single Opsynvi tablet during the trial. “Again, adherence to therapy—just seemed to be easier for our patients … which just makes treatment on our end simpler as well,” one noted.
The only drawbacks to Opsynvi, clinicians said, would be cost and health insurance coverage.
Almost all clinicians who were asked endorsed Opsynvi as a first-line approach for patients who had yet to receive treatment. “Absolutely [I would use as a first-line treatment], most of my patients in naïve get the combination, but as separate pills,” one said.
Of the three clinicians that would not prescribe Opsynvi as a first-line therapy, two said they would start with separate medications initially to monitor side effects. “You don’t know do the adverse events come from drug A or from drug B,” one of them said.
In real-world settings, all clinicians who were asked felt that Opsynvi could help mitigate issues with treatment adherence, benefit a broader population, and improve patients’ health-related quality of life. “Well, of course it can be [improve adherence in patients],” one said. “It is always more advantageous to use [one pill] once a day than two or three times a day.”
All the clinicians also mentioned that double combination therapy with Opsynvi could improve the implementation of the European Society of Cardiology/European Respiratory Society (ESC/ERS) 2022 guidelines that recommend this approach.
“Future research on the single-tablet [Opsynvi] should focus on leveraging real-world data to better understand its utility and impact in clinical practice, as aspects such as medication adherence are challenging to demonstrate within the confines of controlled clinical trial settings,” the researchers concluded. “Until such data are available, these insights from qualitative interviews are an initial source of information on the use of [Opsynvi].”
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