u-62840 and Scleroderma--Limited

To assess the efficacy and safety of continuous subcutaneous infusion of treprostinil, a stable prostacyclin analogue, for treating pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD).. Two multicenter, randomized, double-blind, placebo-controlled, prospective trials of treprostinil vs placebo in 470 patients with PAH.. A subset of 90 patients with PAH and CTD, including systemic lupus erythematosus, diffuse scleroderma, limited scleroderma, and mixed CTD/overlap syndrome.. Patients received either treprostinil (initiated at 1.25 ng/kg/min, and titrated upward) or placebo via continuous subcutaneous infusion. The maximum dose of treprostinil allowed was 22.5 ng/kg/min.. Six-minute walk (6MW) distance and dyspnea-fatigue scores were determined at baseline, and at 6 weeks and 12 weeks. Hemodynamic measures were obtained at baseline and at 12 weeks.. At baseline, most patients had New York Heart Association class III symptoms. The mean baseline 6MW distance was 289 m (range, 60 to 448 m). The mean dose of treprostinil at week 12 was 8.4 ng/kg/min (range, 1.25 to 17.5 ng/kg/min). After 12 weeks, the change in cardiac index from baseline was + 0.2 +/- 0.08 L/min/m(2) in the treprostinil group and - 0.07 +/- 0.07 L/min/m(2) in the placebo group (p = 0.007). The pulmonary vascular resistance index decreased by 4 +/- 2 U x m(2) in the treprostinil group and increased by 1 +/- 1 U x m(2) in the placebo group (p = 0.006). The placebo-corrected median improvement from baseline in 6MW distance was 25 m in treprostinil-treated patients (p = 0.055); this improvement appeared to be dose related. Dyspnea fatigue scores also improved in the treprostinil group compared with the placebo group (p = 0.014). Adverse events included infusion site pain and typical side effects related to prostaglandins, and were tolerated by most patients.. Continuous subcutaneous infusion of treprostinil in patients with PAH associated with CTD improved exercise capacity, symptoms of PAH, and hemodynamics.

Topics: Adolescent; Adult; Aged; Child; Connective Tissue Diseases; Double-Blind Method; Epoprostenol; Exercise Tolerance; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Injections, Subcutaneous; Lupus Erythematosus, Systemic; Male; Middle Aged; Mixed Connective Tissue Disease; Prospective Studies; Scleroderma, Limited; Scleroderma, Systemic; Treatment Outcome; Walking

A 50-year-old woman with a medical history significant for limited scleroderma (SSc) complicated by interstitial lung disease (ILD) and pulmonary arterial hypertension presented to our institution with acute on chronic shortness of breath. Ten years before presentation, she was diagnosed with SSc. Two years before presentation, she was found to have ILD, for which she was started on mycophenolate mofetil and low-dose prednisone. One year before presentation, she noted worsening dyspnea on exertion (New York Heart Association Functional Class III) and required supplemental oxygen, up to 5 L, despite findings of stable ILD on a maintenance dose of mycophenolate mofetil. A subsequent right heart catheterization showed findings consistent with severe pulmonary arterial hypertension: right atrial pressure of 19 mm Hg, pulmonary arterial pressure of 98/39 mm Hg with a mean pulmonary arterial pressure of 58 mm Hg, right ventricular pressure of 59/6 mm Hg, pulmonary arterial wedge pressure of 10 mm Hg, cardiac output of 4.2 L/min with a cardiac index of 2.7 L/min/m

Topics: Antihypertensive Agents; Dyspnea; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Middle Aged; Scleroderma, Limited