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June 06, 2023
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Combination therapy in patients with new pulmonary arterial hypertension often delayed

Fact checked byKristen Dowd
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Key takeaways:

  • In patients with pulmonary arterial hypertension, many initially receive just one drug of the combination therapy.
  • Cardiopulmonary comorbidities occurred in both those taking one or both drugs of the therapy.

WASHINGTON — Only 8% of patients with pulmonary arterial hypertension initiating combination therapy were given both medications on the same day, according to research presented at the American Thoracic Society International Conference.

Sumeet Panjabi

“Since a vast majority of patients are still not escalated to dual combination therapy, we expect these findings will spur clinicians to assess their PAH patient’s risk status early and often and consider the latest 2022 ESC/ERS Guidelines to initiate or rapidly escalate to dual combination therapy with a phosphodiesterase-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA),” Sumeet Panjabi, PhD, senior director of Real World Value & Evidence at Janssen Scientific Affairs, told Healio.

Infographic showing that 8% of patients with PAH on combination therapy were given both drugs on the same day
Data were derived from Paoli C, et al. Real-world use of upfront combination therapy in pulmonary arterial hypertension (PAH) patients. Presented at: American Thoracic Society International Conference; May 19-24, 2023; Washington, D.C.

“For patients and their families, it is imperative that they have an understanding of available treatment options to manage their PAH and discuss their goals with their clinician,” he added. “According to the 2022 ESC/ERS Guidelines, treatment should be optimized/escalated to achieve the goal of low-risk status.”

In a retrospective cohort study of patients from the IQVIA PharMetrics Plus dataset, Panjabi and colleagues assessed adults with PAH between October 2013 and March 2021 to evaluate usage of PAH combination therapy, time to the therapy, who is chosen for the therapy and comorbidities.

Included patients were newly diagnosed with PAH, new users of PAH treatment and had a claim for either of the drugs in the combination therapy, according to the abstract. The second drug of the combination therapy had to be added within 91 days of receiving the first medication to qualify a patient as part of the combination therapy group.

Within the dataset, 1,956 adults (mean age, 58.16 years; 44% men) were on one PAH medication (n = 219 on macitentan; n = 1,737 on a PEDE5i), and 258 adults (11.7%; mean age, 55.41 years; 30.2% men) ended up receiving both, with more than half (65%) receiving macitentan first. According to the abstract, 21 patients were given both drugs on the same day.

“The data shows that only approximately 12% of newly diagnosed and treated PAH patients prescribed a PDE5i or macitentan initiated on combination therapy (PDE5i/macitentan) within 3 months from diagnosis,” Panjabi told Healio.

When evaluating treatment discontinuation, researchers found that more patients on PAH monotherapy stopped taking PDE5i (46.2%) compared with macitentan (3.7%), according to the study poster. This finding was also observed in the combination therapy group, with more patients discontinuing PDE5i (29.5%) than macitentan (15.5%).

Additionally, there were patients in each group that started different medications for PAH, including 16.8% of patients on monotherapy and 2.8% of patients on combination therapy.

“The proportion utilizing dual combination therapy with a PDE5i and macitentan in the sample was less than 20% at the end of 6 months,” Panjabi said. “We did see that over time utilization of dual combination therapy increased from approximately 9% to approximately 18% after the publication of the 2015 ESC/ERS guidelines.”

In terms of patient characteristics, researchers observed significant differences between both groups when assessing age, sex and Charlson Comorbidity Index scores, with a lower mean score in the monotherapy group than combination therapy group (3.22 vs. 3.74).

According to Panjabi, cardiopulmonary comorbidity prevalence was “similar” in both treatment groups, with these comorbidities found in 75.5% of patients on monotherapy and 85.7% of patients on combination therapy.

When assessing the types of comorbidities, researchers found that coronary artery disease (monotherapy, 24.3% vs. combination therapy, 24%) and diabetes (45% vs. 40%) were comparable between groups. Notably, obesity and hypertension occurred in a greater proportion of patients on combination therapy than monotherapy (obesity, 36% vs. 28.8%; hypertension, 79.1% vs. 69.2%).

“This data adds to the literature regarding the potential under-optimization of PAH-approved therapies in real-world practice in the U.S.,” Panjabi told Healio. “In future studies, we would like to assess the impact of combination therapy on outcomes such as hospitalization in real-world settings.”