Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura.

Background: In acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia, and tissue ischemia. Caplacizumab, an anti-von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, inhibits interaction between von Willebrand factor multimers and platelets.

Methods: In this double-blind, controlled trial, we randomly assigned 145 patients with TTP to receive caplacizumab (10-mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter.

Efficacy and safety of sublingual tablets of house dust mite allergen extracts: Results of a dose-ranging study in an environmental exposure chamber.

Background: In a natural field study, sublingual tablets of house dust mite (HDM) allergen extracts (STG320) were efficacious in treating HDM-associated allergic rhinitis.

Objectives: We sought to assess the efficacy and safety of 3 doses of STG320 in an environmental exposure chamber.

Methods: In this randomized, double-blind study, adults with HDM-associated allergic rhinitis were given a daily sublingual tablet containing placebo or STG320 at a dose of 500IR, 300IR, or 100IR (IR, index of reactivity) for 6 months.

Sustained efficacy and safety of a 300IR daily dose of a sublingual solution of birch pollen allergen extract in adults with allergic rhinoconjunctivitis: results of a double-blind, placebo-controlled study.

Background: Allergic rhinoconjunctivitis (ARC) due to birch pollen is a growing health concern in Europe. Here, we report the efficacy and safety of 300IR birch pollen sublingual solution administered discontinuously for 2 consecutive years to patients with birch-associated allergic rhinoconjunctivitis.

Methods: Birch pollen-allergic adults were randomized in this double blind study to 300IR birch pollen sublingual solution or placebo, daily, starting 4 months before and continuing through the pollen season for two pollen seasons.

Efficacy and safety of sublingual tablets of house dust mite allergen extracts in adults with allergic rhinitis.

Background: Preliminary studies have suggested the efficacy of sublingual tablets of house dust mite (HDM) extracts in adults with allergic rhinitis.

Objectives: We sought to assess the efficacy and safety of 2 doses of HDM sublingual tablets over 1 treatment year and the subsequent immunotherapy-free year.

Methods: Adults with HDM-associated allergic rhinitis were randomized in a double-blind, placebo-controlled study to receive 500 index of reactivity (IR) tablets, 300IR tablets, or placebo administered once daily for 1 year and were followed for the subsequent year.

Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: the importance of allergen-specific serum IgE.

Background: Previous trials have demonstrated the efficacy, safety, and optimal dosage of the 5-grass pollen sublingual tablet for adults and children with grass pollen-induced allergic rhinoconjunctivitis.

Objectives: We sought to evaluate the efficacy and safety of 300 index of reactivity (IR) 5-grass pollen sublingual tablet in US adults.

Methods: Adults with grass pollen allergy and Rhinoconjunctivitis Total Symptom Scores of 12 or greater (scale, 0-18) during the previous grass pollen season were randomized in a double-blind, placebo-controlled study to receive 300IR 5-grass pollen sublingual tablet or placebo starting 4 months before and continuing through the pollen season.

Automated telecommunication to obtain longitudinal follow-up in a multicenter cross-sectional COPD study.

Background: It can be challenging to maintain longitudinal follow-up of subjects in clinical studies. COPDGene is a multicenter, observational study designed to identify genetic factors associated with COPD and to characterize COPD-related phenotypes. To obtain follow-up data on patient's vital status and outcomes, the COPDGene Longitudinal Follow-up (LFU) Program was developed to supplement its parent study.

Effectiveness of omalizumab in reducing corticosteroid burden in patients with moderate to severe persistent allergic asthma.

Background: Asthma guidelines advocate maintaining asthma control while minimizing corticosteroid exposure.

Objective: To assess the reduction in corticosteroid burden during long-term treatment and the corresponding impact of this reduction on asthma control, lung function, and inflammation in patients with moderate to severe allergic asthma.

Methods: We conducted a pooled analysis (N = 1,071) of 2 similarly designed, randomized, double-blind, placebo-controlled omalizumab trials and their extension phases.

Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma.

Background: Although specific immunotherapy is a valuable treatment option for patients with allergic asthma, the potential for systemic allergic reactions has limited its use, especially for patients with symptomatic disease.

Objective: To evaluate omalizumab's effect on the tolerability of specific immunotherapy in patients with symptomatic persistent asthma not adequately controlled with inhaled corticosteroids.

Methods: This multicenter, double-blind, parallel-group study randomized patients to treatment with omalizumab or placebo, after which they received specific immunotherapy to at least 1 of 3 perennial aeroallergens (cat, dog, and house dust mite) according to a 4-week, 18-injection cluster regimen, followed by 7 weeks of maintenance therapy.

Efficacy of omalizumab in cat-allergic patients with moderate-to-severe persistent asthma.

Cat allergen (Fel d 1) is a pervasive and common trigger of exacerbations in sensitized patients with IgE-mediated asthma. This study was designed to evaluate the effect on asthma-related outcome measures of adding omalizumab to current treatment in patients with moderate-to-severe persistent asthma and cat allergen sensitivity. A pooled analysis was conducted of two double-blind, placebo-controlled, 28-week pivotal U.

Treatment of chronic autoimmune urticaria with omalizumab.

Background: Approximately 45% of patients with chronic urticaria have an IgG autoantibody directed to the alpha-subunit of the high-affinity IgE receptor (chronic autoimmune urticaria, CAU) leading to cutaneous mast cell and basophil activation. Treatment of allergic asthma with omalizumab produces rapid reduction in free IgE levels and subsequent decrease in Fc epsilon RI expression on mast cells and basophils. If this occurs in CAU, cross-linking of IgE receptors by autoantibody would be less likely, reducing cell activation and urticaria/angioedema.

Efficacy of montelukast during the allergy season in patients with chronic asthma and seasonal aeroallergen sensitivity.

Background: Montelukast has proven efficacy in the treatment of chronic asthma and seasonal allergic rhinitis, but it has not been evaluated in the subpopulation of asthmatic patients with seasonal asthma symptoms.

Objective: To determine the effectiveness of montelukast treatment in improving the control of asthma symptoms during the allergy season in patients with active asthma and seasonal aeroallergen sensitivity.

Methods: Adults with a history of chronic asthma who are also symptomatic during the allergy season and with skin test sensitivity to seasonal aeroallergens were enrolled in a randomized, parallel-group, multicenter study with a 1-week, single-blind, placebo run-in period followed by 3 weeks of double-blind treatment during the spring of 2004.

Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor therapy in HIV-infected patients.

Boosted protease inhibitor regimens combine ritonavir with a second, 'boosted' protease inhibitor to enhance patient exposure to the latter agent, thereby preventing or overcoming resistance and allowing less frequent dosing, potentially improving adherence. The advantages offered by ritonavir boosting are primarily attributable to the drug's pharmacokinetic properties. Ritonavir's inhibition of the cytochrome P-450 CYP3A4 enzyme reduces the metabolism of concomitantly administered protease inhibitors and changes their pharmacokinetic parameters, including area under the curve (AUC), maximum concentration (Cmax), minimum concentration (Cmin) and half-life (t1/2).

Open-label study of a twice-daily indinavir 800-mg/ritonavir 200-mg regimen in HIV-infected adults failing a protease inhibitor regimen.

There is no standard treatment of HIV-infected patients who fail protease inhibitor (PI)-containing antiretroviral therapy. This open-label, noncomparative 24-week study with a 24-week extension evaluated the efficacy, safety, and tolerability of twice-daily indinavir/ritonavir 800/200 mg plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) in this population. Presented here are the results of the 24-week study.

Open-label study of a twice-daily indinavir 800-mg/ritonavir 100-mg regimen in protease inhibitor-naive HIV-infected adults.

Low-dose ritonavir can boost plasma levels of indinavir, thereby enhancing its antiretroviral activity despite less frequent dosing. In this open-label, noncomparative, 24-week trial with a 24-week extension phase, HIV-infected protease inhibitor (PI)- and lamivudine-naive adults received indinavir/ritonavir 800 mg/100 mg plus stavudine and lamivudine every 12 hours. The proportions of patients achieving plasma HIV RNA (vRNA) <400 and <50 copies/mL were analyzed with data as observed (DAO) and intention-to-treat models using generalized estimating equations (GEE) or counting noncompleters as failures (NC = F).

A multicenter, randomized, double-blind, placebo-controlled, 8-week trial of the efficacy and tolerability of once-daily losartan 100 mg/hydrochlorothiazide 25 mg and losartan 50 mg/hydrochlorothiazide 12.5 mg in the treatment of moderate-to-severe essential hypertension.

Background: Many patients with moderate-to-severe hypertension require multiple drug therapy to achieve blood-pressure goals. Fixed-dose combination therapy with losartan and hydrochlorothiazide may be useful in this population.

Objective: This study was conducted to obtain additional data on the antihypertensive efficacy and tolerability of once-daily, fixed-dose combinations of losartan and hydrochlorothiazide.

The effect of a losartan-based treatment regimen on isolated systolic hypertension.

This study was conducted to compare the antihypertensive efficacy and tolerability, over 12 weeks, of a losartan-based treatment regimen and placebo in patients with isolated systolic hypertension. Three hundred eight patients > or =35 years of age with isolated systolic hypertension, defined as trough sitting blood pressure between 140 and 200 mm Hg systolic and between 70 and 89 mm Hg diastolic, were randomized to losartan 50 mg (n=157) or placebo (n=151) once daily, with titration as necessary to achieve a goal trough sitting systolic blood pressure (SBP) <140 mm Hg. At baseline, mean trough sitting SBP was 140-159 mm Hg in 20.