OBJECTIVES: While a prior indirect treatment comparison (ITC) indicated no significant efficacy disparity between riociguat and selexipag for PAH, limitations arose due to variations in trial designs. This study aimed to address these limitations by conducting additional ITC scenarios, comparing riociguat + endothelin receptor antagonists (ERA) versus selexipag+ERA+sildenafil. Additionally, a cost-minimization analysis (CMA) was performed from the Brazilian public health perspective.

METHODS: Leveraging data from the REPLACE and GRIPHON trials, including a GRIPHON subanalysis, we conducted an ITC between riociguat+ERA and selexipag+ERA+sildenafil. Given the unavailability of tadalafil and macitentan in Brazil, patients using these therapies were excluded when feasible. Since there were differences in the endpoints measured between trials and lack of some detailed information, we conducted three comparison scenarios. Scenario 1: WHO functional class III (WHO FC-III) patients treated with riociguat+ERA vs. WHO FC-III patients treated with selexipag+ERA+sildenafil comparing not achieving the primary endpoint of each trial; Scenario 2: WHO FC-III patients treated with riociguat+ERA vs. WHO FC-III patients treated with selexipag+ERA+sildenafil comparing the morbimortality endpoint; Scenario 3: WHO FC-III patients treated with riociguat+ERA vs. any WHO FC patients treated with selexipag+ERA+sildenafil comparing not achieving the primary endpoint of each trial. Using “meta” and “metafor” packages with R software the Bucher method calculated odds ratios (OR) and 95% confidence intervals (95% CI). The CMA compared yearly costs based on label posology and publicly available prices.

RESULTS: Riociguat+ERA vs. selexipague+ERA+sildenafil: Scenario 1: OR 0.77 (95% CI: 0.33–1.79); Scenario 2: OR 0.26 (95% CI: 0.03–2.31); Scenario 3: OR 0.92 (95% CI: 0.41–2.07). The CMA indicated yearly costs of BRL 106,931 versus BRL 118,023 for riociguat+ERA vs. selexipag+ERA+sildenafil, respectively.

CONCLUSIONS: In line with prior findings, all ITC scenarios showed no statistically significant efficacy difference. Therefore, implementing a CMA, we identified a potential BRL 11,092/year/patient cost savings with riociguat doublet therapy.