Participant Characteristics

Twenty-six patients were interviewed and their demographic characteristics are summarized in Table 1. Most patients recruited into the study were female (84.6%) and described themselves as white (82.6%) non-Hispanic (79.2%). Three (13.0%) patients described themselves as Asian or Asian American and one (4.3%) patient described themselves as black or African American. Mean age was 48.3 years, ranging from 23 to 72 years. Data received post analysis confirmed that the patients recruited for this interview study were similar to those in the A DUE clinical trial.

Table 1 Patient demographic characteristics (N = 26 total)

A total of 18 clinicians took part in the interviews and demographic characteristics are summarized in Table 2. Most clinicians were male (82.4%), and mean age was 51 years, ranging between 37 and 63 years. Data on race was not collected. Most clinicians (58.8%) described themselves as cardiologists working for a multi-specialty hospital (70.6%). Sixteen clinicians had more than 10 years of experience working with patients with PAH and saw between five and 50 patients with PAH per year.

Table 2 Clinician background informationPatient Interviews

Insights from the patient interviews are presented in the following subsections. Table 3 presents key concepts from patient interviews regarding M/T FDC along with exemplary quotes. This shows that patients discussed multiple positive experiences and benefits associated with the M/T FDC.

Table 3 Key concepts from the patient interviews regarding M/T FDCPrevious Experience with Treatment of PAH

All patients spoke about the pill burden they experienced before taking part in the clinical trial. Interviewed patients indicated that they were taking between one and 15 pills per day for PAH and comorbidities (mean = 8 pills per day), although one patient did not give a number and instead just described it as “so many”. Of the 26 patients interviewed, 14 had previously received PAH-specific treatment. This result is based on patient feedback provided during the interview only and may not necessarily reflect clinical information reported during the trial, i.e., some patients may consider oxygen or diuretics as PAH-specific treatment. Treatment for comorbidities and/or PAH contributed to the feeling of pill burden, e.g., “I mean, they’re little pieces of time here and there… it is actually time-consuming”. Patients discussed how the number of pills they were taking was something that concerned them, and that they often felt overwhelmed by the number of pills they had to take for both PAH and other comorbidities (see Supplemental Table S4). Patients also discussed the impact of pill burden on their mental health, including feeling sad, or the psychological burden of managing their medication, e.g., “Making me sad, because I was like, ‘they [there] are too many pills and this is progressing fast’” (see additional quotes in Supplemental Table S4). Of the 14 patients who had previously received PAH-specific treatment, five spontaneously highlighted they had, on occasion, forgotten to take their PAH treatment. See Supplemental Table S4 for additional quotes.

Treatment Experience During the Double-Blind Period of the Clinical Trial

All 26 patients described their experience of taking four pills in the double-blind period of the clinical trial, and highlighted they had to do more planning each week and day to ensure they had all the pills needed. This included setting alarms and creating routines, e.g., “That was rough. It took me a little bit to adjust [to taking so many tablets]. I had to put a reminder in my phone” and “I had to constantly remember to put it [trial medication [4 pills]) in my bag when I left the house. Like this… So I knew I [wouldn’t] shouldn’t forget it.” Patients discussed how this extra work and planning impacted their emotional well-being by increasing levels of stress and worry: “I’m telling you… I was always stressed out thinking [about all of the pills]”.

Most patients (24/26) said they did not forget to take the medication in the double-blind portion, despite it requiring more time management and planning, as they knew this was something they had to do as part of the trial. Managing this large number of pills impacted patients’ lives by increasing stress, worry, and anxiety. Nine patients described how the large number of pills caused them worry and concern in terms of making sure they did not miss a dose, took them at the correct times, and that the large number of pills caused them more stress, e.g., “I worry so much and there are so many pills, right? So what do I do? I separate them. I leave it in a corner, on the table. And then I know I have to take it. Then when I take it, I put it away. So I don’t forget whether I took it [trial medication] or not”. Most patients (12/21; five patients did not answer this question) said that taking four tablets was not convenient for them, one patient was unsure about whether it was convenient, and eight patients found it just as convenient as taking any other medication.

Treatment Experience During the Open-Label Period of the Clinical Trial

In comparison to the double-blind portion of the clinical trial, all 26 patients expressed positive thoughts, feelings, and experiences with the single M/T FDC treatment, and when asked, indicated that they preferred the single FDC tablet in the open-label period over the multiple tablets in the double-blind period, e.g., “It’s way easier. It’s a lot easier [taking one tablet]. And I don’t have to… follow a book, I just… open the bottle and… take one [laughs]”. Patients shared positive feedback about how the FDC tablet was convenient, aided adherence, and had a positive impact on their day-to-day lives, improving overall medication management and stress levels. Five patients spontaneously reported that fewer pills made them feel less “sick.” All patients highlighted they were satisfied with the M/T FDC, that it was easy to take and manage, and that they did not miss a dose during the open-label portion of the trial. In contrast to the double-blind portion of the trial, no patients mentioned any negative impacts of taking M/T FDC as part of their day-to-day lives.

In addition, 23/26 patients explicitly highlighted how they would like to continue taking the medication: “I do [wish to continue treatment] and I’m really worried that I won’t be able to continue, you know?” and “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. …I wish I could do that for all of my stuff”. The remaining three patients were not asked this question and did not raise this point spontaneously.

Clinician Interviews

Table 4 presents key concepts from clinician interviews regarding M/T FDC along with exemplary quotes.

Table 4 Key concepts from the clinician interviews regarding M/T FDCTypical Approach to Treating Patients with PAH

Interviewed clinicians were asked to discuss their typical approach to treating PAH. Ten of the 18 clinicians suggested they typically start patients on combination therapy and the remaining clinicians said that they typically start patients on monotherapy with quick progression to combination therapy. Clinicians suggested that patients typically take between five and 14 pills for PAH and other comorbidities combined: between two and seven pills for PAH and between three and seven pills for other comorbidities. As part of this discussion, clinicians were asked if they were aware of the ESC/ERS 2022 guidelines for treating PAH. The ESC/ERS guidelines recommend initial double therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase type 5 inhibitor (PDE5i) for patients with idiopathic, heritable, connective tissue disease (CTD)-associated PAH or drug-associated PAH and who have no cardiopulmonary comorbidities and are at low or intermediate risk of 1-year mortality [1, 14, 15]. All clinicians, regardless of country, stated that they were aware of these guidelines and typically tried to follow them: “we try… to follow the international guidelines, the European guidelines. So, we start with combination treatment… almost in all of the patients… that present in functional class 2, 3, and in an outpatient setting”. Another clinician discussed the guidance on treating PAH in the presence of comorbidities: “Yes, I know. If there is comorbid cardiopulmonary disease, then monotherapy. If there is no comorbid cardiopulmonary disease, then combination therapy is recommended from the initial period. For the low and moderate risk group… the guidelines suggest ambrisentan/tadalafil or macitentan/tadalafil, but if the patient is in the high-risk group, the guidelines emphasize that we should start with a triple combination with IV prostanoids”. See Supplemental Table S5 for additional quotes.

Clinician Feedback on M/T FDC During Clinical Trial

All 18 clinicians, regardless of their country, spoke positively about the M/T FDC tablet: “Again, adherence to therapy—just seemed to be easier for our patients [when taking the M/T FDC], which just makes treatment on our end simpler as well”. All clinicians described how any reduction in the number of pills required would be appreciated by patients and, in their opinion, would improve adherence to the treatment regimen in the clinical trial and the real world, and, ultimately, this would mean the patients are more likely to be treated according to the 2022 ESC/ERS guidelines [1]. According to the clinicians, the only drawbacks to M/T FDC therapy would be cost and health insurance coverage. One clinician shared feedback they had received from a patient who they described as being distraught at the idea of going back to multiple pills: “anecdotally we did have patients that were a little bit distraught at the concept of having to go back to multiple pills a day at… completion of the study… I think the patient-centered side of things… there was a lot of benefit… psychiatrically for the patients.”

Suitability of M/T FDC for Treatment-Naïve Patients

Almost all clinicians who were asked (14/17; one clinician did not discuss this topic) endorsed the M/T FDC as a first-line approach for treatment-naïve patients, if the treatment was approved: “Yeah. Absolutely [I would use as a first-line treatment], most of my patients in naïve get the combination, but as separate pills”. These 14 clinicians described how they typically start patients on these treatments and could see themselves using the FDC tablet for treatment-naïve patients. The remaining three clinicians (3/17) reported that they would not prescribe the M/T FDC to treatment-naïve patients as a first-line approach. Of these, two said they would use separate medications initially to monitor side effects, “you don’t know do the adverse events come from drug A or from drug B”, while the third said they would not prescribe the M/T FDC to treatment-naïve patients as a first-line approach as a result of their country’s treatment approach dictated by the health system.

Potential Impact of Single FDC Tablet in the Real World

All clinicians who were asked (17/17; one clinician was not asked this question) felt that M/T FDC could help mitigate issues with adherence to treatment: “Well, of course it can be [improve adherence in patients]. It is always more advantageous to use [one pill] once a day than two or three times a day”. All clinicians reported that M/T FDC therapy would benefit the wider population and have a positive impact on patients’ adherence in the real world: “For everyone, patient adherence will be significantly better… if [the] patient will still… see a lower number of pills on his hand every morning”. In addition, these clinicians (17/17) felt that M/T FDC could improve adherence and positively impact patients’ health-related quality of life (HRQoL) or psychological health.

All clinicians also discussed that, by making it easier to put patients on double combination therapy, M/T FDC could improve the implementation of ESC/ERS guidelines that recommend initial double combination therapy of an ERA and PDE5i for patients without cardiopulmonary comorbidities: “So I think it [M/T FDC] will have a very significant impact to [on] the clinical treatment condition [guidelines]. And also, I think the majority of our clinical physicians will accept it”. As clinician and patient feedback indicated that M/T FDC could improve adherence, this could in turn mean patients are more likely to adhere to treatments and thus follow ESC/ERS guidelines: “Well, I think it will be absolutely suitable [for everyone], and it will be… an interesting improvement… if we can offer them a combination in a single tablet…. this is positive, of course”.