Treatment with Adcirca (tadalafil) plus Opsumit (macitentan) can provide functional benefits and lessen symptoms in newly diagnosed patients with pulmonary arterial hypertension (PAH), results from a clinical trial show.
The data will be discussed at the upcoming CHEST Annual Meeting 2019, to be held Oct. 19-23 in New Orleans, La. An oral presentation, titled “Initial Treatment Combination with Macitentan and Tadalafil in Patients with Pulmonary Arterial Hypertension: Results from the OPTIMA Study,” will be given by Olivier Sitbon, MD, PhD, from Université Paris–Sud.
Opsumit is a ERA therapy, which means it reduces the production of endothelin, subsequently decreasing blood vessel constriction, and lowering the blood pressure in the pulmonary arteries. Adcirca is a PDE-5 inhibitor that works by relaxing the smooth muscle cells of arteries, leading to vasodilation and a reduction of blood pressure.
The Phase 4 open-label OPTIMA trial (NCT02968901) — sponsored by Actelion, the developer of Opsumit — was designed to assess the impact of the Adcirca plus Opsumit combo treatment as a first-line therapy in newly diagnosed PAH patients.
The trial enrolled 46 participants in France who had been diagnosed with PAH and mild-to-moderate physical impairment due to the disease (WHO functional class II-III). None of the patients had received any PAH treatment before entering the study.
Participants started treatment with 10 mg of Opsumit and 20 mg of Adcirca, at the same time, given orally, once daily. After approximately 8 days, the dose of Adcirca was increased to 40 mg.
After 16 weeks of treatment, participants showed reduced pulmonary resistance — a measure that shows how well the blood can flow in blood vessels — by about 47% compared with assessments from before the therapy’s start.
Evaluation of the patients’ physical capacity also showed that the combo treatment had a beneficial effect. In general, participants were able to walk 35.8 meters more than before in the six-minute walk distance test, and approximately 63% of patients showed improved functional ability.
“This study is encouraging regarding the dual upfront therapy with these agents in patients with PAH,” Victor Test, MD, co-chair of the CHEST scientific program committee and professor at Texas Tech University Health Sciences Center, said in a press release. “This study adds additional strength to the evidence for upfront dual oral therapy.”
Regarding safety, most of the participants (93.5%) experienced at least one adverse reaction during the trial. A total of 13 patients (28.3%) experienced serious adverse reactions, and three (6.5%) discontinued the treatment. Three patients died during the study, with the causes of death reported as cardiac arrest, heart failure, and multi-organ failure with sepsis.
The most common adverse reactions reported were headache, edema (fluids accumulation), diarrhea, dyspnea (shortness of breath), anemia, and asthenia (lack of energy).
The OPTIMA trial results suggest that initial treatment with Adcirca plus Opsumit “was well tolerated in patients with PAH, and led to hemodynamic improvement, as well as improvements in functional parameters and risk profile,” the researchers said.
“Our findings add new evidence to the benefit of initial oral double combination therapy in patients with pulmonary hypertension,” Sitbon concluded.