US Database Study of Clinical Burden and Unmet Need in Recurrent Pericarditis.

Background Patients with recurrent pericarditis (RP) may develop complications, multiple recurrences, or inadequate treatment response. This study aimed to characterize disease burden and unmet needs in RP. Methods and Results This retrospective US database analysis included newly diagnosed patients with RP with ≥24 months of continuous history following their first pericarditis episode. RP was defined as ≥2 pericarditis episodes ≥28 days apart. Some patients had ≥2 recurrences, while others had a single recurrence with a serious complication, ie, constrictive pericarditis, cardiac tamponade, or a large pericardial effusion with pericardiocentesis/pericardial window. Among these patients with multiple recurrences and/or complications, some had features relating to treatment history, including long-term corticosteroid use (corticosteroids started within 30 days of flare, continuing ≥90 consecutive days) or inadequate treatment response (pericarditis recurring despite corticosteroids and/or colchicine, or other drugs [excluding NSAIDs] within 30 days of flare, or prior pericardiectomy). Patients (N=2096) had hypertension (60%), cardiomegaly (9%), congestive heart failure (17%), atrial fibrillation (16%), autoimmune diseases (18%), diabetes mellitus (21%), renal disease (20%), anxiety (21%), and depression (14%). Complications included pericardial effusion (50%), cardiac tamponade (9%), and constrictive pericarditis (4%). Pharmacotherapy included colchicine (51%), NSAIDs (40%), and corticosteroids (30%), often in combination. This study estimates 37 000 US patients with RP; incidence was 6.0/100 000/year (95% CI, 5.6‒6.3), and prevalence was 11.2/100 000 (95% CI, 10.6‒11.7). Conclusions Patients with RP may have multiple recurrences and/or complications, often because of inadequate treatment response and persistent underlying disease. Corticosteroid use is frequent despite known side-effect risks, potentially exacerbated by prevalent comorbidities. Substantial clinical burden and lack of effective treatments underscore the high unmet need.

Pharmacokinetic and safety profiles of repeated-dose prophylactic micafungin in children and adolescents undergoing hematopoietic stem cell transplantation.

Micafungin is a potent echinocandin antifungal that can be used for both prophylaxis and treatment of Candida infections. This open-label study assessed the pharmacokinetics and safety profile of prophylactic micafungin in children and adolescents (aged 4 mo to 16 y) undergoing hematopoietic stem cell transplantation. Patients received once-daily doses of either 1 or 1.5 mg/kg micafungin, based on their body weight, for 10 to 14 days. In total, 40 patients received micafungin. Area under the plasma micafungin concentration-time curve was highest in patients aged 6 to 11 years in the 1.5 mg/kg treatment group. Peak plasma micafungin concentration displayed no age-related differences, but was higher in the 1.5 mg/kg versus the 1 mg/kg group. Clearance at steady state by weight and volume of distribution by weight were considerably higher in patients aged 4 months to 5 years. Results from this study show that age and body weight affect micafungin pharmacokinetics in pediatric patients undergoing hematopoietic stem cell transplantation.

Safety and pharmacokinetic profiles of repeated-dose micafungin in children and adolescents treated for invasive candidiasis.

BACKGROUND: Micafungin is an echinocandin with proven efficacy against a broad range of fungal infections, including those caused by Candida spp. OBJECTIVE: To evaluate the safety and pharmacokinetics of once-daily 3 mg/kg and 4.5 mg/kg micafungin in children with proven, probable or suspected invasive candidiasis. METHODS: Micafungin safety and pharmacokinetics were assessed in 2 phase I, open-label, repeat-dose trials. In Study 2101, children aged 2-16 years were grouped by weight to receive 3 mg/kg (≥25 kg) or 4.5 mg/kg (<25 kg) intravenous micafungin for 10-14 days. In Study 2102, children aged 4 months to <2 years received 4.5 mg/kg micafungin. Study protocols were otherwise identical. RESULTS: Safety was analyzed in 78 and 9 children in Studies 2101 and 2102, respectively. Although adverse events (AEs) were experienced by most children (2101: n=62; 2102: n=9), micafungin-related AEs were less common (2101: n=28; 2102: n=1), and the number of patients discontinuing due to AEs was low (2101: n=4; 2102: n=1). The most common micafungin-related AEs were infusion-associated symptoms, pyrexia and hypomagnesemia (Study 2101), and liver function abnormalities (Study 2102). The micafungin pharmacokinetic profile was similar to that seen in other studies conducted in children, but different than that observed in adults. CONCLUSIONS: In this small cohort of children, once-daily doses of 3 mg/kg and 4.5 mg/kg micafungin were well tolerated. Pharmacokinetic data will be combined in a population pharmacokinetic analysis to support US dosing recommendations in children.

Hepatitis B DNA vaccine induces protective antibody responses in human non-responders to conventional vaccination.

A novel DNA vaccine against hepatitis B virus was administered intraepidermally by particle-mediated epidermal delivery (PMED) to 16 human subjects who demonstrated absent or non-sustainable responses to conventional hepatitis B vaccination. Eleven subjects received three doses of vaccine at 56-day intervals, and five subjects received only a single vaccination. Each dose of vaccine contained 4 microg of plasmid DNA encoding the hepatitis B surface antigen (HBsAg). The vaccine was safe and well tolerated. Remarkably, the DNA vaccine elicited antibody responses in 12 of the 16 subjects after a licensed subunit vaccine failed to induce a lasting response after >/=3 vaccinations. This study provides evidence in humans for protective immunogenicity of a particle-mediated DNA vaccine in subjects who have responded suboptimally to conventional vaccination.