Background/Purpose:

PAH associated with CTD (PAH-CTD) has a worse prognosis than idiopathic/familial PAH. Here we report a prospective subgroup analysis of patients with PAH-CTD from the PATENT studies of the soluble guanylate cyclase stimulator, riociguat.

Methods:

PATENT-1 was a 12-week, randomized Phase III trial in which patients with PAH received either riociguat individually dose-adjusted up to 2.5 mg tid (2.5 mg–maximum group), riociguat up to 1.5 mg tid (1.5 mg–maximum group; exploratory), or placebo. The primary endpoint was change from baseline in 6-minute walking distance (6MWD). Long-term safety and survival were assessed during the PATENT-2 open-label extension.

Results:

In PATENT-1, 111 patients had PAH-CTD (systemic sclerosis [SSc; n=66, including diffuse SSc and limited SSc], non-SSc CTD [n=39], and unspecified CTD [n=6], derived post-hoc from the medical history using MedDRA preferred terms). Seventy PAH-CTD patients were pretreated with PAH-specific therapy, of whom 59 were receiving endothelin receptor antagonists. Of the overall group of PAH-CTD patients, 71, 15, and 25 were randomized to riociguat 2.5 mg–maximum, riociguat 1.5 mg–maximum, and placebo, respectively. At baseline, mean±SD 6MWD was 348±70 m in the riociguat 2.5 mg–maximum group and 361±88 m in the placebo group. At Week 12, there was an improvement in 6MWD in the 2.5 mg–maximum riociguat group (+18 m) and a deterioration in the placebo group (–8 m) (Figure 1; PAH-CTD population; intention-to-treat, imputed values). Consistent with other studies, the least-squares mean treatment difference between riociguat and placebo (+28 m) in patients with PAH-CTD was lower than that observed in the overall study population (+36 m). In the SSc subgroup the placebo-corrected mean treatment difference in change from baseline was mostly based on the deterioration in exercise capacity on placebo (Figure 1). At the March 2014 cut-off for PATENT-2, 70 patients with PAH-CTD had been receiving treatment for ≥2 years. In PATENT-2, efficacy in 6MWD was maintained over 2 years in patients with PAH-CTD receiving riociguat. Clinical worsening events were experienced by <30% of patients with PAH-CTD in the PATENT-2 study, with a higher rate of events occurring in the SSc subcategory, which was driven by patients needing to start new PAH-specific treatments. At 2 years, similar survival rates (95% CI) were observed for patients with PAH-CTD, SSc, idiopathic/familial PAH and the overall population: 93% (85–97%), 94% (82–98%), 93% (89–96%), and 93% (90–95%), respectively. Riociguat had a similar safety profile in patients with PAH-CTD as observed in the overall population.

Conclusion:

In patients with PAH-CTD, riociguat was associated with long-term improvements in exercise capacity. The 2‑year survival rates in riociguat-treated patients with PAH-CTD were high and similar to patients with idiopathic/familial PAH.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-riociguat-in-patients-with-pulmonary-arterial-hypertension-pah-associated-with-connective-tissue-disease-ctd/