u-62840 and Lupus-Erythematosus--Systemic

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

Malignant atrophic papulosis (Köhlmeier-Degos disease; MAP) is an uncommon endotheliopathy with pathological findings similar to the vascular lesions of systemic sclerosis. These two disorders can overlap. When associated with visceral lesions, MAP has been considered almost universally and rapidly fatal. A recent report described dramatic response to treatment with eculizumab, but disease progression after initial response to therapy has occurred.. We describe the clinical and pathologic findings in two patients, one with MAP and the other with MAP like lesions, who received treatment with subcutaneous treprostinil. One patient had an overlap syndrome with features of systemic lupus erythematosus (SLE) and scleroderma and severe pulmonary hypertension. She also had very extensive MAP like cutaneous lesions. There was no evidence of central nervous system (CNS) disease and laparoscopy revealed no visible MAP lesions on the serosa of the small bowel. The second patient had experienced life-threatening disease progression despite ongoing eculizumab therapy. During this treatment, he had developed CNS and bladder involvement with neurologic symptoms and gross hematuria.. Patient one was placed on therapy with treprostinil for her pulmonary hypertension, but in the months subsequent to initiation of treatment, dramatic and complete resolution of cutaneous MAP like lesions and disabling digital pain occurred. In patient two, therapy with treprostinil was temporally associated with clearing of hematuria, resolution of CNS symptoms and improvement in MRI findings.. Treprostinil may offer a second effective treatment approach to individuals with MAP or "rescue therapy" to those in whom eculizumab treatment has failed to maintain suppression of disease activity.

Topics: Adolescent; Adult; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Lupus Erythematosus, Systemic; Male; Malignant Atrophic Papulosis; Scleroderma, Systemic

Subcutaneous prostacyclin (treprostinil) is an effective short-term treatment for pulmonary hypertension. The most frequently described adverse effect-pain in the area of injection-rarely requires that treatment be withdrawn. Sildenafil is a selective fosfodiesterase-5 inhibitor with pulmonary vasodilating effects. We describe the use of sildenafil as a substitute for treprostinil in a patient with pulmonary hypertension associated with lupus erythematosus. Treatment with treprostinil was discontinued due to uncontrollable abdominal pain.

Topics: Abdominal Pain; Adult; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Lupus Erythematosus, Systemic; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents