Phase 3 trial of lumasiran for primary hyperoxaluria type 1: A new RNAi therapeutic in infants and young children.

Purpose: Primary hyperoxaluria type 1 (PH1) is a rare, progressive, genetic disease with limited treatment options. We report the efficacy and safety of lumasiran, an RNA interference therapeutic, in infants and young children with PH1.

Methods: This single-arm, open-label, phase 3 study evaluated lumasiran in patients aged <6 years with PH1 and an estimated glomerular filtration rate >45 mL/min/1.

Population-Based Pharmacokinetic and Exposure-Efficacy Analyses of Peginterferon Beta-1a in Patients With Relapsing Multiple Sclerosis.

Peginterferon beta-1a reduced annualized relapse rate as compared with placebo and was approved to treat multiple sclerosis patients. A population pharmacokinetic and an exposure-efficacy model were developed to establish the quantitative relationship between pharmacokinetics and annualized relapse rate. The pharmacokinetics was well described by a 1-compartment model with first-order absorption and linear elimination kinetics.

Incidence, characterization, and clinical impact analysis of peginterferon beta1a immunogenicity in patients with multiple sclerosis in the ADVANCE trial.

Background: Efficacy of interferon beta in multiple sclerosis (MS) can be dampened in patients who develop neutralizing antidrug antibodies (NAbs). Peginterferon beta1a is an interferon conjugated with a polyethylene glycol (PEG) moiety. Pegylation increases a drug's half life and exposure, and may also reduce immunogenicity.

COMPARE: Pharmacokinetic profiles of subcutaneous peginterferon beta-1a and subcutaneous interferon beta-1a over 2 weeks in healthy subjects.

Aim: Subcutaneous (s.c.) peginterferon beta-1a injected once every 2 weeks and s.

Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE.

Objective: To evaluate the efficacy and safety of subcutaneous peginterferon beta-1a over 2 years in patients with relapsing-remitting multiple sclerosis in the ADVANCE study.

Methods: Patients were randomized to placebo or 125 µg peginterferon beta-1a every 2 or 4 weeks. For Year 2 (Y2), patients originally randomized to placebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks.

Pharmacokinetics, pharmacodynamics, and safety of peginterferon beta-1a in subjects with normal or impaired renal function.

Peginterferon beta-1a was efficacious in a Phase 3 relapsing multiple sclerosis trial, and its safety profile was consistent with other beta interferons. This study evaluated the impact of renal impairment on the pharmacokinetics and pharmacodynamics (neopterin elevation; a biomarker of pharmacological activity induced by interferon beta-1a) of peginterferon beta-1a following a single subcutaneous dose at 63 μg (n = 5) or 125 μg (n = 30). The results showed a fractional increase in area-under-the-concentration-time curve (AUC [30-53%]) and peak serum concentration (Cmax [26-42%]) in subjects with mild, moderate, and severe renal impairment, versus healthy subjects; AUC and Cmax were similar for healthy subjects and end-stage-renal-disease patients receiving hemodialysis.

Single-use autoinjector for peginterferon-β1a treatment of relapsing-remitting multiple sclerosis: safety, tolerability and patient evaluation data from the Phase IIIb ATTAIN study.

Objectives: A sub-study to evaluate safety, tolerability, ease-of-use and patient satisfaction with a single-use autoinjector administering subcutaneous peginterferon-β1a (a pegylated interferon-β1a in clinical development) in a subset of relapsing-remitting multiple sclerosis (MS) patients participating in ATTAIN, a long-term dose-frequency blinded extension of the Phase III randomized ADVANCE study.

Methods: Over 8 weeks, patients self-administered peginterferon-β1a 125 µg or placebo every 2 weeks (two injections via manual pre-filled syringe [PFS]; two injections via single-use autoinjector). Primary end points were incidence of adverse events (AEs), patient assessment of injection pain score (10-point Visual Analog Scale), and clinician assessment of injection site reactions (ISRs).

Pegylated interferon β-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study.

Background: Subcutaneous pegylated interferon (peginterferon) beta-1a is being developed for treatment of relapsing multiple sclerosis, with less frequent dosing than currently available first-line injectable treatments. We assessed the safety and efficacy of peginterferon beta-1a after 48 weeks of treatment in the placebo-controlled phase of the ADVANCE trial, a study of patients with relapsing-remitting multiple sclerosis.

Methods: We did this 2-year, double-blind, parallel group, phase 3 study, with a placebo-controlled design for the first 48 weeks, at 183 sites in 26 countries.

Strains of Ehrlichia chaffeensis in southern Indiana, Kentucky, Mississippi, and North Carolina.

Rates of infection of Amblyomma americanum (L.) by Ehrlichia chaffeensis were compared in 100 ticks collected from sites in each of four states: Indiana, North Carolina, Kentucky, and Mississippi. The overall infection rates were similar among sites, ranging from 1 to 4%.

Deep vein thrombosis in orthopedic surgery.

We compared 315 patients with deep vein thrombosis who underwent major orthopedic surgery with 618 who underwent general surgery in a prospective registry of consecutive ultrasound-confirmed deep vein thrombosis patients. Orthopedic patients had fewer indwelling central venous catheters (14.0% vs.

Gastrointestinal complications after 3 months of dual antiplatelet therapy for drug-eluting stents as assessed by wireless capsule endoscopy.

Little is known about the frequency of symptomatic and asymptomatic gastrointestinal complications of dual antiplatelet therapy. We recruited 30 patients between 18 and 80 years who were started on aspirin and clopidogrel following percutaneous coronary intervention with drug-eluting stents. We hypothesized that the 3 months of dual antiplatelet therapy would be associated with frequent upper gastrointestinal endoscopic abnormalities.

Deep-vein thrombosis in the elderly.

Venous thromboembolism, including deep-vein thrombosis and pulmonary embolism, is a major source of morbidity and mortality among elderly patients. To improve our understanding of elderly patients with deep-vein thrombosis, we compared 1932 patients with deep-vein thrombosis aged 70 years or older with 2554 nonelderly patients in a prospective registry of consecutive ultrasound-confirmed deep-vein thrombosis patients. The mean age of elderly patients was 78.

Deep vein thrombosis in patients with chronic kidney disease.

Deep vein thrombosis (DVT) is a poorly understood complication of chronic kidney disease (CKD). The objective of our analysis was to profile DVT patients with and without CKD. We defined CKD as patients requiring dialysis or patients having nephrotic syndrome.

Heart failure in patients with deep vein thrombosis.

Patients with heart failure (HF) are particularly vulnerable to the development of venous thromboembolism (VTE) and its related complications of pulmonary embolism and right ventricular failure. To improve our understanding of the clinical characteristics, prophylaxis, and initial management of patients with HF and deep vein thrombosis (DVT), we compared 685 patients with a history of HF with 3,890 patients without HF in a prospective registry of 5,451 consecutive patients with ultrasound-confirmed DVT. We excluded 876 patients for whom data regarding HF status were incomplete.

Venous thromboembolism in patients undergoing surgery: low rates of prophylaxis and high rates of filter insertion.

Patients who undergo surgery are at a high risk of developing venous thromboembolism (VTE). To further define the demographics, comorbidities, and risk factors of VTE in patients undergoing major surgery, we analyzed 1,375 hospitalized non-orthopedic surgery patients in a prospective registry of 5,451 patients with ultrasound confirmed deep vein thrombosis (DVT) from 183 hospitals in the United States. Extremity edema (67.

Chronic obstructive pulmonary disease and deep vein thrombosis: a prevalent combination.

Background: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for venous thromboembolism (VTE). We analyzed a large US deep vein thrombosis (DVT) registry to explore the profile of patients with COPD and VTE.

Methods: Demographics, symptoms, risk factors, prophylaxis, and initial management of 668 (12%) patients with COPD were compared to 3,907 patients without COPD from a prospective registry of 5,451 consecutive patients with ultrasound-confirmed DVT at 183 institutions in the United States.

Venous thromboembolism in patients with active cancer.

Patients with cancer have an increased risk of venous thromboembolism (VTE). To further define the demographics, comorbidities, and risk factors of VTE in these patients, we analyzed a prospective registry of 5,451 patients with ultrasound confirmed deep vein thrombosis (DVT) from 183 hospitals in the United States. Cancer was reported in 1,768 (39%), of whom 1,096 (62.

Double trouble for 2,609 hospitalized medical patients who developed deep vein thrombosis: prophylaxis omitted more often and pulmonary embolism more frequent.

Background: Hospitalized patients with medical illness are especially susceptible to the development of venous thromboembolism (VTE).

Methods: To improve our understanding of the demographics, comorbidities, risk factors, clinical presentation, prophylaxis, and treatment of hospitalized medical patients with deep vein thrombosis (DVT), we evaluated hospitalized medical patients in a prospective registry of 5,451 consecutive ultrasound-confirmed DVT patients at 183 institutions in the United States.

Results: Of those patients who participated in the registry, 2,609 (48%) were hospitalized medical patients.