Adempas May Help PAH-SSc Patients When Adcirca Fails, Case Report Suggests

Switching to Adempas (riociguat) is a potential therapeutic option for patients with pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc) who failed to improve when treated with phosphodiesterase type-5 (PDE-5) inhibitors such as Adcirca (tadalafil), a case series study reported.

The research, “Replacing a phosphodiesterase-5 inhibitor with riociguat in patients with connective tissue disease-associated pulmonary arterial hypertension: a case series,” was published in the journal Pulmonary Circulation.

The therapeutics available for PAH are now varied and include prostanoids, PDE-5 inhibitors, endothelin receptor antagonists, and the soluble guanylate cyclase stimulator Adempas.

PDE-5 inhibitors are frequently used as first-line therapy due to their lower cost and easy use. Additional therapies can be added sequentially or combined with PDE-5 inhibitors.

However, patients with PAH associated with connective tissue disease (PAH-CTD), such as SSc, are characterized by poorer responses to therapy and increased mortality risks when compared with patients who have PAH alone. Therefore, patients with PAH-SSc may show an insufficient response to treatment with a PDE-5 inhibitor.

In this case series, a research team described three patients with PAH-SSc who were switched from a PDE-5 inhibitor treatment to Adempas due to insufficient clinical response. In all three cases, the patients’ diagnosis with SSc was confirmed following the criteria of the American College of Rheumatology.

The first case was a 33-year-old woman who began treatment with the PDE-5 inhibitor Adcirca. After slight improvement initially, the patient’s symptoms worsened, and the dual endothelin receptor antagonist Tracleer (bosentan) was added to her therapy regimen. While her respiratory status initially improved, follow-up pulmonary tests showed again decline in her respiratory health. Later, doctors changed treatment from Adcirca to Adempas, and the patient’s respiratory status improved.

The second case reported was a 62-year-old woman diagnosed with limited SSc, who later developed moderate PAH. The patient was administered the PDE-5 inhibitor Revatio (sildenafil), leading to a marked improvement of her respiratory status. She remained stable for the next five years, but then symptoms worsened. Treatment with Revatio was switched to Adempas at a concentration showing no significant side effects.

The patient’s respiratory status following the change was stable to slightly improved. Later, clinicians introduced the endothelin receptor antagonist Opsumit (macitentan) to further improve the patient’s hemodynamic characteristics.

The third case discussed was that of a 67-year-old woman diagnosed with PAH-CTD due to limited SSc. The patient exhibited advanced symptoms. She was first treated with the vasodilator Remodulin (treprostinil) and then moved to the PDE-5 inhibitor Adcirca. After a period of improvement, the patient’s clinical status began to decline.

Clinicians first tried adding Opsumit to the treatment regimen, but it failed to produce significant improvements. Adcirca was then switched to Adempas, which led to significant improvements.

Overall, “these three cases demonstrate that in patients with PAH-CTD who have an inadequate response to a PDE-5i, switching to riociguat has the potential to improve clinical and hemodynamic parameters and showed a favorable tolerability profile in clinical trials and in our select patients,” the team concluded.