Efficacy and safety of inhaled extrafine beclomethasone dipropionate in adults with asthma: a randomized, parallel-group, dose-ranging study (BEAM).

Introduction: This manuscript describes a Phase II, dose-ranging, randomized, double-blind, placebo- and active-controlled, parallel-group study conducted to identify the appropriate dose of beclomethasone dipropionate (BDP) to be used in a single-inhaler extrafine formulation triple combination of BDP, formoterol fumarate and glycopyrronium.Methods: Patients aged 18-75 years with poorly-controlled asthma, receiving low/medium-dose inhaled corticosteroid (ICS), and who had forced expiratory volume in the 1st second (FEV1) 50-85% predicted, were randomized to inhale BDP 50, 200 or 400 µg twice daily (BID; total daily doses of 100, 400 and 800 µg), placebo, or the active comparator QVAR® 160 µg BID, all via pressurized metered-dose inhalers for 8 weeks. The primary objective was to evaluate superiority of BDP over placebo for change from baseline in pre-dose morning FEV1 at Week 8. ClinicalTrials.gov: NCT03084718.Results: Of 610 patients randomized, 559 (91.6%) completed the study. For pre-dose morning FEV1 at Week 8, BDP 200 µg BID was superior to placebo, with a statistically significant difference of 113 ml (95% CI 18, 209); differences vs placebo for BDP 50 and 400 µg BID were not significant (44 [-52, 140] and 93 [-3, 188] ml, respectively). Secondary efficacy endpoint results supported the primary endpoint in identifying BDP 200 µg BID as the appropriate dose. Adverse events were experienced by 23.5, 25.0 and 30.6% patients with BDP 50, 200 and 400 µg BID, 34.7% with placebo, and 30.6% with the active comparator.Conclusion: In this dose-ranging study, BDP 200 µg BID offered the optimal balance of efficacy and safety in patients with asthma poorly controlled on low/medium-dose ICS.Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Biologic targeted therapy in allergic asthma.

OBJECTIVE: To review the structure, function, clinical utility, and safety of current biologic targeted therapies being used for the treatment of asthma. DATA SOURCES: Medical literature obtained from PubMed and OVID searches from June to November 2013. STUDY SELECTIONS: Studies were selected based on article impact, relevance, and clinical significance. Particular emphasis was placed on articles discussing therapies targeted at IgE, interleukin (IL)-4, IL-4 receptor, IL-5, IL-13, tumor necrosis factor-α, CRTh2, and toll-like receptors 7 and 9. RESULTS: Since the approval of omalizumab in 2003, the development of biologic asthma therapies has grown at a remarkable pace. With approximately 30 drugs currently in clinical trials and dozens more in development, the future of asthma biologic therapies is promising. Despite several well-publicized setbacks, researchers remain focused on elucidating the complex pathophysiology of asthma. The hope is that asthma biologic therapies will eventually be tailored to an individual's asthma phenotype. With more than 300 million people worldwide affected by asthma and with roughly 5% to 10% of this population living with severe, uncontrolled asthma, the need for new biologic therapies is great. CONCLUSION: The introduction of each new biologic therapy into clinical trials has been associated with great anticipation, but the outcome of these trials, in many cases, has led to disappointment. Given the lack of overwhelming positive responses, these results have emphasized that asthma is a complex clinical syndrome with multiple underlying genotypes and clinical phenotypes. It has become abundantly clear that it is very unlikely that there is one "magic bullet" to cure all patients with asthma.

The mechanisms, causes, and treatment of anaphylaxis.

Anaphylaxis is a severe life-threatening systemic reaction that offers many challenges to the clinician. The incidence of anaphylaxis is significant in the general population and an important cause of morbidity and mortality. While the most common causes of anaphylaxis include drugs, foods, and venoms, other important etiologies must be considered. The etiology of anaphylaxis is classically based on IgE mediated hypersensitivity but multiple mechanisms may be involved. The clinical presentation of anaphylaxis may be extremely variable with a broad differential diagnosis which will be outlined. Although the diagnosis of anaphylaxis can many times be based on a careful history and physical examination, there are laboratory and skin tests which may be helpful in establishing a diagnosis in some cases. The cornerstone of treatment of anaphylaxis remains epinephrine. Other supportive therapies will be discussed.

Allergies to sulfonamide antibiotics and sulfur-containing drugs.

OBJECTIVE: To provide a literature review and clinical summary of the evaluation and management of sulfonamide drug reactions. DATA SOURCES: Published English-language medical literature. STUDY SELECTION: Selected trials of drug desensitization protocols. RESULTS: Obtaining a detailed history is invaluable in assessing a history of reactions to sulfonamide medications, because allergy to these drugs remains a clinical diagnosis at present. Numerous efficacious drug desensitization protocols for management have been published and are reviewed in detail. CONCLUSIONS: The term sulfa allergy is imprecise and misleading and therefore should be discouraged. There are important distinctions between sulfonylarylamines (antimicrobial sulfonamides), nonarylamine (nonantimicrobial) sulfonamides, and sulfones, with regard to allergic and other adverse drug reactions. Most reactions to sulfonylarylamines probably result from multifactorial immunologic and toxic metabolic mechanisms, whereas less is known about the precise mechanisms of reactions to other sulfur-containing drugs.