Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Targeting the Prostacyclin Pathway with Selexipag in Patients with Pulmonary Arterial Hypertension Receiving Double Combination Therapy: Insights from the Randomized Controlled GRIPHON Study

Background: In pulmonary arterial hypertension (PAH), combination therapy is an important treatment strategy. Although randomized controlled trial data are available to support the combination of two therapies, data regarding triple combination therapy are few. Objective: The phase III GRIPHON trial enrolled 1156 patients with PAH, including 376 receiving background double combination therapy. We evaluated the efficacy and safety of selexipag as a third agent in these patients and further analyzed this subgroup according to symptom burden at baseline as indicated by World Health Organization (WHO) functional class (FC). Methods: In this post hoc analysis, hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using Cox proportional-hazard models to determine response to selexipag versus placebo on the composite primary endpoint of morbidity/mortality. Baseline characteristics and adverse events were summarized descriptively. Results: Of 376 patients receiving background endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE-5i) therapy, 115 had WHO FC II symptoms and 255 had WHO FC III symptoms at baseline. The impact on the primary endpoint of adding selexipag versus placebo to double combination therapy was consistent with the effect in the overall population (HR 0.63; 95% CI 0.44–0.90) as well as in patients with WHO FC II and III symptoms. Compared with the overall population, discontinuations due to an adverse event were higher when selexipag was added to background double combination therapy; no safety concerns were identified. Conclusion: The addition of selexipag to background double combination therapy with an ERA and PDE-5i provides an incremental benefit similar to that seen in the overall population, including in patients with WHO FC II or III symptoms at baseline. ClinicalTrials.gov Identifier NCT01106014. Electronic supplementary material The online version of this article (10.1007/s40256-017-0262-z) contains supplementary material, which is available to authorized users

Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial

International audienc

Clinical Pharmacology of Endothelin Receptor Antagonists Used in the Treatment of Pulmonary Arterial Hypertension

International audiencePulmonary arterial hypertension (PAH) is a devastating life-threatening disorder characterized by elevated pulmonary vascular resistance leading to elevated pulmonary arterial pressures, right ventricular failure and ultimately death. Vascular endothelial cells mainly produce and secrete endothelin (ET-1) in vessels that lead to a potent and long-lasting vasoconstrictive effect in pulmonary arterial smooth muscle cells. Along with its strong vasoconstrictive action, ET-1 can promote smooth muscle cell proliferation. Thus, ET-1 blockers have attracted attention as an antihypertensive drug and the ET-1 signaling system has paved a new therapeutic avenue for the treatment of PAH. The present chapter outlines not only the current understanding of the pathogenic role played by ET-1 signaling systems in the pathogenesis of PH, but also on the clinical pharmacology of endothelin receptor antagonists (ERA) used in the treatment of PAH

Cryptococcus neoformans Infections Differ Among Human Immunodeficiency Virus (HIV)–Seropositive and HIV-Seronegative Individuals: Results From a Nationwide Surveillance Program in France

International audienceAmong 1107 cryptococcosis cases from the French surveillance network (2005–2020), the proportion of HIV-seronegative individuals has recently surpassed that of HIV-seropositive individuals. We observed marked differences in patient characteristics, disease presentations, cryptococcal antigen results, infecting species, and mortality according to HIV serostatus