A chronic inflammatory disease of the airways, asthma affects approximately 315 million people worldwide. With 5 – 10% (≈15 – 31.5 million) of these people suffering from severe asthma, research into treatments for the disease is ongoing. A study recently looked at an alternative treatment to help manage severe asthma in patients relying upon oral glucocorticoids.
Asthma is typically characterized by an ongoing inflammatory process in the airways, where eosinophils (white blood cells which play an important role in fighting diseases) have been found to be a part of the pathological process. Sputum eosinophils are used as biomarkers of airway inflammation and a tool for assessing and diagnosing asthma patients, along with disease severity and treatment outcome.
In order to manage symptoms, people suffering from severe asthma rely heavily on frequent or maintenance use of oral glucocorticoids. During an asthma attack, the inside walls of the airways swell and narrow resulting in difficulty breathing. Oral glucocorticoids are able to reduce inflammation and swelling in the airways, making them an excellent treatment for asthma sufferers. However, oral glucocorticoids adversely affect the health of patients and their quality of life.The main issue with oral glucocorticoids is they are distributed to all parts of the body as opposed to inhaled corticosteroids (glucocorticoids are a class of corticosteroids) which only go to the lungs. Therefore, long term use can lead to multiple side effects such as peptic ulcers, weight gain, glucose intolerance, bloating, elevated blood pressure and osteoporosis.
In a 28-week randomized, double-blind study published in The New England Journal of Medicine by Nair and colleagues, the use of benralizumab (shown to significantly reduce the incidence of asthma exacerbations) as an effective therapy to reduce reliance on oral glucocorticoids and manage severe asthma was investigated.
Prior to the trial, all patients were treated continuously for 6 months with oral glucocorticoids. During the trial, 220 patients with severe asthma underwent treatment with either benralizumab (administered subcutaneously for the first 3 doses every 4 weeks), then the treatment group was divided and patients received subsequent treatments either every 4 weeks or 8 weeks or placebo. The effects of treatment versus placebo on the reduction of a patient’s oral glucocorticoid dose whilst maintaining control of their asthma were assessed.
Patients were required to record daily their lung function measurements using a handheld spirometer and asthma symptoms (including morning assessment, number of nighttime awakenings, rescue medication use and evening assessment of activity impairment). Blood and induced sputum samples were taken from a subset of patients (60 random patients) to analyze sputum eosinophil levels.
The primary outcome observed in this trial were patients who relied on oral glucocorticoids and were receiving benralizumab treatment were able to significantly reduce their dose of oral glucocorticoids whilst maintaining control of their asthma compared to those receiving the placebo. The odds of reducing oral glucocorticoid treatment was more than four times higher for the treatment group as opposed to those in the placebo group.
Furthermore, those patients receiving treatment as opposed to the placebo also had substantially lower asthma exacerbation rates and less exacerbation-related hospital visits. Also, compared to the placebo group, annual exacerbation rates were lowered by 55% in patients who received treatment every 4 weeks and 70% in patients who received it every 8 weeks.
Nair and colleagues noted that limitations of this study included the study was only run for 28 weeks and longer-term trials involving asthma patients dependent on oral glucocorticoids would be needed to draw definitive conclusions on the efficacy and safety of benralizumab use as a potential alternative treatment to oral glucocorticoids. Also, in 20% of patients in the treatment group, there was no reduction seen in oral glucocorticoids and it remains unclear why. Future studies may also be needed to assess the long-term safety and efficacy of benralizumab on eosinophil depletion as opposed to normalization of eosinophil counts.
For the millions of people suffering from severe asthma, this study provides hope to reduce the use of oral glucocorticoids by possibly replacing treatment with benralizumab to control and maintain their condition. Thus, potentially improving quality of life to patients who are also affected by the adverse side effects known to occur due to long-term use of oral glucocorticoids.
Written by Lacey Hizartzidis, PhD
Parameswaran Nair, M.D., Ph.D., Sally Wenzel, M.D., Klaus F. Rabe, M.D., Ph.D., Arnaud Bourdin, M.D., Ph.D., Njira L. Lugogo, M.D., Piotr Kuna, M.D., Ph.D., Peter Barker, Ph.D., Stephanie Sproule, M.Math., Sandhia Ponnarambil, M.D., and Mitchell Goldman, M.D., for the ZONDA Trial Investigators. Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma, N Engl J Med 2017; 376:2448-2458, June 22, 2017DOI: 10.1056/NEJMoa1703501.
Bandyopadhyay A, Roy PP, Saha K, Chakraborty S, Jash D, Saha D. Usefulness of induced sputum eosinophil count to assess severity and treatment outcome inasthma patients. Lung India. 2013 Apr;30(2):117-23. doi:10.4103/0970-2113.110419. PubMed PMID: 23741092; PubMed Central PMCID:PMC3669551.
George L, Brightling CE. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease. Ther Adv Chronic Dis. 2016 Jan;7(1):34-51.doi: 10.1177/2040622315609251. Review. PubMed PMID: 26770668; PubMed CentralPMCID: PMC4707428.
Oral Corticosteroids. Palo Alto Medical Foundation website www.pamf.org. Accessed June 29, 2017.