Early Use of Triple Oral Therapy May Lower Hospitalizations for PAH

Adding a third oral medication early on in treatment may improve the effectiveness of standard-of-care treatment in patients with pulmonary arterial hypertension (PAH).

The insight comes from a comparative effectiveness study, which found that the addition of selexipag (Uptravi) to double oral therapy (DOT) with an endothelin receptor antagonist (ERA) and a phosphodiesterase type 5 inhibitor (PDE5i) reduced the hospitalization risk for patients with PAH and the risk of their disease progressing.¹

PAH concept | image credit: Ahmad - stock.adobe.com

“Understanding long-term health care use and clinical outcomes, such as hospitalization, under various therapies is central for improving the lives of patients with PAH given that hospitalizations among these patients are common, costly, and highly predicative of mortality risk,” wrote the researchers based on their findings, published in JAMA Network Open.

The oral formulation of selexipag received the greenlight from the FDA in 2015. The treatment is also available in an intravenous formulation, approved in 2021 for patients unable to take oral treatment.²

Among the 3000 patients included in the study, the addition of oral selexipag reduced the risk even further when the treatment was added on within 3 months of DOT initiation, with a 21% reduction in hospitalization from all causes (adjusted hazard ratio [aHR], 0.79; 95% CI, 0.65-0.97), a 25% reduction in hospitalization related to PAH (aHR, 0.75; 95% CI, 0.61-0.92), and a 26% reduction in progression of disease (aHR, 0.74; 95% CI, 0.61-0.90).¹

The study findings highlight the importance of initiating selexipag treatment within 3 months, as the benefit of the treatment waned as initiation time was prolonged. When selexipag was initiated within 6 months, all-cause hospitalization was reduced by 18% (aHR, 0.82; 95% CI, 0.72-0.94), PAH-related hospitalization was reduced by 19% (aHR, 0.81; 95% CI, 0.70-0.95) and disease progression was reduced by 18% (aHR, 0.82; 95% CI, 0.70-0.95).

“Studies have suggested that the treatment effect of selexipag on long-term outcomes was impacted by time to initiation of oral selexipag. Our results showed a potential benefit of adding oral selexipag early to an ERA and PDE5i treatment regimen,” explained the researchers.“TOT was associated with the greatest decrease in all-cause hospitalization vs DOT when patients initiated selexipag within 3 months of DOT initiation, and the decrease was smaller or not significant when selexipag was initiated within 6 and 12 months. These results reinforce the potential benefit of early up-front triple therapy of selexipag, macitentan (Opsumit), and tadalafil (cialis) vs double therapy of macitentan, tadalafil, and placebo in preventing PAH-related progression found in the exploratory TRITON study.”

The findings from the study complement those from randomized trials like the TRITON study, as well as the GRIPHON study. The phase 3 GRIPHON study found that selexipag significantly reduced the risk of mortality compared with placebo.³ However, these trials, explained the researchers, include younger and healthier patients that may not be representative of the general PAH population.

To the researchers’ knowledge, the effect of selexipag on a wider range of patients, as done in the current study, has only been previously assessed in a claims data study, which found that initiating the treatment within 12 months of diagnosis carried a lower risk of hospitalizations from all causes, though no difference was found in PAH-related hospitalizations, compared with not receiving a prostacyclin pathway treatment.

References:

1. Burger CD, Tang W, Tsang Y, Panjabi S. Early addition of selexipag to double therapy for pulmonary arterial hypertension. JAMA Netw Open. 2024;7(9):e2434691. doi:10.1001/jamanetworkopen.2024.34691
2. Johnson & Johnson. UPTRAVI^® (selexipag) receives FDA approval for intravenous use in adult patients with pulmonary arterial hypertension (PAH). Press Release. July 30, 2021. Accessed October 1, 2024. https://www.jnj.com/media-center/press-releases/uptravi-selexipag-receives-fda-approval-for-intravenous-use-in-adult-patients-with-pulmonary-arterial-hypertension-pah
3. Sitbon O, Channick R, Chin KM, et al. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015;373(26):2522-2533. doi:10.1056/NEJMoa1503184