Literature Review: Managing Asthma

Literature Review: Managing Asthma: A Challenge for Stakeholders

Asthma is a chronic disease that causes inflammation in the airways of the lungs, with multifactorial pathophysiology.1 According to the Centers for Disease Control and Prevention, asthma affects an estimated 18.9 million adults and 7.1 million children.2 Asthma is a costly disease to treat; the economic burden on society, providers, and payers is substantial. The total annual direct and indirect cost of asthma was $56 billion (2009 dollars) in 2007.2

Despite advances in asthma care and management, asthma remains an unpredictable disease with profound public health implications.3 This underscores the need for improvements in the management and control of asthma. For this literature review, First Report Managed Care (FRMC) identified 2 studies3,4 that examine potential new treatment options for asthma and provide an overview of the findings, including the recently FDA-approved mepolizumab. The interleukin (IL)-5 antagonist is indicated for add-on maintenance treatment of patients with severe asthma who are age 12 years or older and with an eosinophilic phenotype.5

 ASTHMA DRUGS IN THE PIPELINE

McIvor et al4 reviewed a number of therapeutic options for the treatment of symptomatic asthma that are currently in development. Therapies that are in phase 2 and phase 3 development and include: anti-IL agents (benralizumab, re­slizumab, dupilumab, brodalumab, lebrikizumab, and mepolizumab); a chemoattractant receptor-homolo­gous molecule expressed on T-help­er type 2 lymphocyte antagonists (OC000459); a phosphodiesterase-4 inhibitor (roflumilast); and a long-acting muscarinic antagonists (LAMAs [glycopyrronium bromide, umecli­dinium bromide, and tiotropium bromide]).

 For this literature review, FRMC highlights therapies in the anti-IL and LAMA drug classes.

Reslizumab (anti-IL-5) and du­pilumab (anti-IL-4) are 2 anti-IL agents being investigated. In the first phase 3 trial of 953 adult and adolescent patients with moderate-to-severe eosinophilic asthma, results showed that monthly intravenous reslizumab significantly decreased asthma exacerbations (P<.0001) and had a similar adverse event profile compared with placebo. In a 12-week, phase 2 study of 104 patients with moderate-to-severe eosinophilic asthma, results showed that once-weekly subcutaneous administration of dupilumab 300 mg also significantly decreased the incidence of asthma exacerbations compared with placebo (P<.001).4

There are 3 LAMAs being investi­gated in clinical trials of asthma. The tiotropium bromide clinical trial pro­gram is currently the most advanced, according to researchers. Tiotropium bromide, a long-acting anticholinergic bronchodilator, is FDA approved for the treatment of chronic obstructive pulmonary disease.4

Phase 2 and phase 3 studies have shown that the oral bronchodilator is an efficacious add-on to at least inhaled corticosteroid (ICS) mainte­nance therapy across severities of symptomatic asthma. For example, in a 3-way, crossover study of 210 patients with uncontrolled asthma, once-daily tiotropium bromide at 18 μg via an inhaler significantly improved asthma symptoms (P<.001) and lung function compared with a doubling of the ICS dose, and was noninferior to salmeterol in patients with symptomatic asthma.4

Researchers concluded that the results of ongo­ing and future studies of these and other agents may help to address the current unmet need in asthma patients and to determine where these emerging therapies will fit in future asthma treat­ment guidelines.4

 STUDY EXAMINES CHARACTERIZATION OF RESPONSE TO MEPOLIZUMAB

In the second study, Ortega et al3 used a supervised cluster analysis from the DREAM (Dose Ranging Efficacy and Safety With Mepolizumab) study to identify clusters associated with exacerbation rates among 616 patients in mepolizumab and placebo treatment arms.

Blood eosinophils, airway reversibility, and body mass index (BMI) were 3 predictors identified in 4 primary clusters. The results showed that reduction in exacerbations were significantly greater in patients who received mepolizumab (clusters 2, 3, and 4) with raised airway eosinophils. Patients in cluster 2 (n=186), where the main distinctive feature was low airway reversibility (mean, 11%), achieved a 53% reduction in exacerbations with me-polizumab vs placebo. Clusters with higher airway reversibility (mean, 28%) were further divided by BMI. The nonobese and obese (cluster 3 [n=179] and 4 [n=102]) had a 35% and 67% reduction in exacerbations with mepolizumab, respectively, vs placebo. Cluster 4 also had a higher proportion of reported comorbid conditions, including weight gain (24.5%), hypertension (46.1%), and anxiety (16.7%).3—Eileen Koutnik-Fotopoulos

 1. National Heart, Lung, and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma Full Report 2007. National Asthma Education and Prevention Program. US Department of Health & Human Services; National Institutes of Health. www. nhlbi.nih.gov/files/docs/guidelines/asthgdln. pdf. Accessed November 23, 2015.

2. Centers for Disease Control and Prevention. Asthma Facts—CDC’s National Asthma Control Program Grantees. July 2013. www.cdc.gov/ asthma/pdfs/asthma_facts_program_grantees. pdf. Accessed November 23, 2015.

3. Ortega H, et al Cluster analysis and characteriza­tion of response to mepolizumab. A step closer to personalized medicine for patients with severe asthma. Ann Am Thorac Soc. 2014;11(7):1011-1017.

4. McIvor RA. Emerging therapeutic options for the treatment of patients with symptom­atic asthma. Ann Allergy Asthma Immunol. 2015;115(4):265-271.

      5. Nucala [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2015.