Application of the criteria for satisfactory clinical response to riociguat treatment of patients with pulmonary arterial hypertension (PAH) in PATENT-1 and PATENT-2

Introduction

Riociguat is approved for treatment of PAH, based on data from the PATENT-1 study and PATENT-2 extension. This analysis examined PATENT data using a satisfactory clinical response (SCR) outcome measure similar to that used in the AIR and AMBITION studies.

Methods

In PATENT-1, patients received riociguat up to 1.5 mg tid, 2.5 mg tid or placebo for 12 weeks. All patients received riociguat up to 2.5 mg during PATENT-2. The proportion of patients achieving SCR was calculated at PATENT-1 Week 12, and PATENT-2 Week 12. SCR was defined as a ≥10% improvement in 6MWD compared with baseline; World Health Organization functional class I/II, and no clinical worsening.

Results

In PATENT-1 overall, a higher proportion of riociguat-treated patients achieved SCR versus placebo (30% versus 16%). This was also true in treatment-naïve (38% versus 17%) and pretreated patients (22% versus 15%).  In PATENT-2, 41% of patients achieved SCR overall. A greater proportion of former riociguat patients achieved SCR versus former placebo (44% versus 33%), as did treatment-naïve patients versus pretreated (36% versus 46%). Patients achieving components of the SCR had improved clinical worsening-free survival in PATENT-2 (Figure 1).

Conclusions

In PATENT-1, riociguat increased the proportion of patients meeting SCR criteria compared with placebo. SCR achievement increased further in PATENT-2, with similar increases observed in the former placebo and former riociguat arms. The proportion of patients achieving SCR in PATENT-2 was similar to that in the AMBITION study, supporting the use of SCR as a clinical measure of efficacy in PAH patients.