Clinical pharmacology of caplacizumab for the treatment of patients with acquired thrombotic thrombocytopenic purpura.

: Caplacizumab is a humanized anti-von Willebrand Factor (vWF) Nanobody® for the treatment of acquired Thrombotic Thrombocytopenic Purpura (aTTP). Caplacizumab targets the A1-domain of vWF, inhibiting the interaction between vWF and platelets. Clinical studies conducted in aTTP patients confirmed the rapid and sustained complete suppression of the vWF activity using an initial intravenous dose of 10 mg, and a maintenance subcutaneous 10 mg daily dosing regimen, with corresponding favorable efficacy and safety profiles.

Predicting Responders to Reslizumab after 16 Weeks of Treatment Using an Algorithm Derived from Clinical Studies of Patients with Severe Eosinophilic Asthma.

Rationale: Reslizumab is a humanized anti-IL-5 monoclonal antibody used as add-on maintenance treatment for patients with uncontrolled eosinophilic asthma.

Objectives: To predict response and nonresponse to intravenous reslizumab at 52 weeks with an algorithm we developed based on clinical indicators from pivotal clinical trials.

Methods: Patients aged 18 years and older who met Global Initiative for Asthma 4 or 5 criteria and received intravenous reslizumab (n = 321) in two trials ( www.

Evaluation of inhaler technique and achievement and maintenance of mastery of budesonide/formoterol Spiromax® compared with budesonide/formoterol Turbuhaler® in adult patients with asthma: the Easy Low Instruction Over Time (ELIOT) study.

Background: Incorrect inhaler technique is a common cause of poor asthma control. This two-phase pragmatic study evaluated inhaler technique mastery and maintenance of mastery with DuoResp® (budesonide-formoterol [BF]) Spiromax® compared with Symbicort® (BF) Turbuhaler® in patients with asthma who were receiving inhaled corticosteroids/long-acting β2-agonists.

Methods: In the initial cross-sectional phase, patients were randomized to a 6-step training protocol with empty Spiromax and Turbuhaler devices.

Stratification of eosinophilic asthma patients treated with reslizumab and GINA Step 4 or 5 therapy.

Reslizumab, an anti-interleukin-5 monoclonal antibody, significantly reduces exacerbation frequency and improves lung function, asthma control and quality of life in adults with severe eosinophilic asthma, as demonstrated in Phase III studies. This secondary analysis assessed reslizumab's efficacy in patients receiving baseline treatment per Global Initiative for Asthma (GINA) Step 4 and Step 5 guidelines. Pooled data from duplicate, Phase III, reslizumab placebo studies in patients with severe eosinophilic asthma (blood eosinophils ≥400 cells·µL) were stratified by baseline therapy.

Clinical efficacy of omalizumab in chronic spontaneous urticaria is associated with a reduction of FcεRI-positive cells in the skin.

Treatment with omalizumab, a humanized recombinant monoclonal anti-IgE antibody, results in clinical efficacy in patients with Chronic Spontaneous Urticaria (CSU). The mechanism of action of omalizumab in CSU has not been elucidated in detail. To determine the effects of omalizumab on levels of high affinity IgE receptor-positive (FcεRI) and IgE-positive (IgE) dermal cells and blood basophils.

Effect of omalizumab on angioedema in H1 -antihistamine-resistant chronic spontaneous urticaria patients: results from X-ACT, a randomized controlled trial.

Background: Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied.

Objective: The primary objective was to evaluate the efficacy of omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire.

Revision of omalizumab dosing table for dosing every 4 instead of 2 weeks for specific ranges of bodyweight and baseline IgE.

The dosing level and frequency of omalizumab are guided by a dosing table based on total serum immunoglobulin E (IgE) and bodyweight. Using a validated, mathematical simulation model (based on concentration data from 8 studies), we evaluated the impact of a revised omalizumab dosing table (every 4 weeks dosing regimen) on the pharmacokinetic and pharmacodynamic profiles of free and total IgE. Safety analysis, in patients with high levels of exposure to omalizumab, was done using data from the clinical and post-marketing databases.

Healthcare Resource Utilization in Patients Receiving Omalizumab for Allergic Asthma in a Real-World Setting.

Introduction: Inadequately controlled asthma is associated with increased healthcare resource utilization. The eXpeRience registry was initiated to evaluate real-world outcomes in patients receiving omalizumab for uncontrolled persistent allergic asthma. The current analysis of data from the eXpeRience registry focuses on healthcare resource utilization and on absences from work or school.

Omalizumab in asthma: an update on recent developments.

IgE is central to the pathophysiology of allergic asthma. Omalizumab, a humanized anti-IgE mAb, specifically binds free IgE and interrupts the allergic cascade by preventing binding of IgE with its high-affinity FcεRI receptors on mast cells, antigen-presenting cells, and other inflammatory cells. The clinical efficacy of omalizumab has been well documented in a number of clinical trials that involve adults, adolescents, and children with moderate-to-severe and severe allergic asthma.

Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study.

ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed doses. Patients aged 12-75 years with CIU/CSU who remained symptomatic despite treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary end point was change from baseline in weekly itch severity score (ISS) at week 12.

Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy.

Background: Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H1-antihistamines along with 1 or more add-on therapies.

Objectives: We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H₁-antihistamines at up to 4 times the approved dose plus H₂-antihistamines, leukotriene receptor antagonists, or both.

Methods: In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period.

Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria.

Background: Many patients with chronic idiopathic urticaria (also called chronic spontaneous urticaria) do not have a response to therapy with H-antihistamines, even at high doses. In phase 2 trials, omalizumab, an anti-IgE monoclonal antibody [corrected] that targets IgE and affects mast-cell and basophil function, has shown efficacy in such patients.

Methods: In this phase 3, multicenter, randomized, double-blind study, we evaluated the efficacy and safety of omalizumab in patients with moderate-to-severe chronic idiopathic urticaria who remained symptomatic despite H-antihistamine therapy (licensed doses).

Omalizumab and the risk of malignancy: results from a pooled analysis.

Background: Since initial registration, the omalizumab clinical trial database has expanded considerably, with a doubling of patients exposed in the clinical trial environment. Previous pooled data (2003) from phase I to III studies of omalizumab showed a numeric imbalance in malignancies arising in omalizumab recipients (0.5%) compared with control subjects (0.

Familial seropositive rheumatoid arthritis in North American Native families: effects of shared epitope and cytokine genotypes.

Objective: A number of North American native (NAN) populations have high prevalence rates of both rheumatoid arthritis (RA) and the shared epitope (SE). We examined the phenotype and familial incidence of RA in a NAN population, and investigated how the SE and cytokine genes may affect disease risk within affected families.

Methods: NAN patients with seropositive RA or polyarthritis rheumatoid factor (RF) positive juvenile idiopathic arthritis (JIA) were identified from clinical databases.

A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study.

Objective: To evaluate the efficacy and safety of adding intramuscular (IM) gold to the treatment regimen of patients with rheumatoid arthritis (RA) who have a suboptimal response to methotrexate (MTX).

Methods: A randomized, double-blind, double-observer, placebo-controlled multicenter trial of 48 weeks was conducted. Sixty-five RA patients who had a suboptimal response to >/=12 weeks of MTX therapy were randomly assigned to receive weekly IM gold or placebo in addition to MTX.

Glucosamine sulfate and cartilage type II collagen degradation in patients with knee osteoarthritis: randomized discontinuation trial results employing biomarkers.

Objective: To determine whether glucosamine sulfate has an effect on cartilage type II collagen degradation in patients with knee osteoarthritis (OA).

Methods: A randomized, double blind, placebo controlled glucosamine discontinuation trial was conducted in 137 subjects with knee OA, who had had at least moderate relief of knee pain after starting glucosamine. Subjects were randomized to glucosamine at prestudy dose or placebo at an equivalent dose.

Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis.

Objective: To assess the efficacy of glucosamine sulfate in knee osteoarthritis (OA).

Methods: A 4-center, 6-month, randomized, double-blind, placebo-controlled glucosamine discontinuation trial was conducted in 137 current users of glucosamine with knee OA who had experienced at least moderate improvement in knee pain after starting glucosamine. Study medication dosage was equivalent to the dosage of glucosamine taken prior to the study (maximum 1,500 mg/day).

Therapeutic potential of targeting IL-1 and IL-18 in inflammation.

Interleukin (IL)-1 and IL-18 are cytokines that play a major role in autoimmune and inflammatory human disease. Both cytokines drive a wide range of pro-inflammatory effector networks in many cell types and use common signal transduction cascades. IL-1, IL-18 and other members of the IL-1 superfamily are expressed at elevated levels in tissue and fluid samples isolated from patients with many chronic inflammatory diseases.

Site specificity of regular health club exercise on muscle strength, fitness, and bone density in women aged 29 to 45 years.

Objective: To determine the effect of regular exercise with use of stepper or skier machines on muscle strength, cardiovascular fitness, bone mineral density, and markers of bone turnover in women aged 29 to 45 years.

Subjects And Methods: We evaluated 14 women: 5 who used a stepper machine for at least 3 hours each week for 2 years, 4 who used a skier machine for at least 3 hours each week for 2 years, and 5 who did not exercise (controls). All women were healthy, had no history of disease or medication use known to affect bone metabolism, and had normal levels of estradiol-17beta.

Infrared spectroscopy: shedding light on synovitis in patients with rheumatoid arthritis.

Objectives: It is difficult to determine the extent of synovial involvement early in the course of rheumatoid arthritis. A spectroscopic technique was used to characterize the synovium of the small finger joints in both early and late rheumatoid arthritis. This synovium was also compared against normal joints.

Contact activation in shock caused by invasive group A Streptococcus pyogenes.

Objectives: The aim of this study was to characterize abnormalities of coagulation in mice with experimental, invasive group A, streptococcal shock, in an attempt to explain the prolongation of the activated partial thromboplastin time identified in patients with streptococcal toxic shock syndrome.

Design: A longitudinal descriptive animal model study of coagulation times and single coagulation factors in mice infected with Streptococcus pyogenes. This was followed by an experimental study to determine whether streptococci or streptococcal products could activate the human contact system in vitro.