Session Type: ACR Plenary Session
Session Time: 11:00AM-12:30PM
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.
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.
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.
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.
To cite this abstract in AMA style:Denton CP, Coghlan JG, Ghofrani HA, Grimminger F, He J, Riemekasten G, Vizza D, Boeckenhoff A, Meier C, de Oliveira Pena J, Humbert M. Efficacy and Safety of Riociguat in Patients with Pulmonary Arterial Hypertension (PAH) Associated with Connective Tissue Disease (CTD) [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-riociguat-in-patients-with-pulmonary-arterial-hypertension-pah-associated-with-connective-tissue-disease-ctd/. Accessed January 25, 2021.
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