Currently, steroids are the main treatment option for asthma and COPD exacerbations. Each exacerbation increases loss of lung function, and some patients may never return to their baseline after an exacerbation. However, recent research suggests clinicians may not need to automatically recommend glucocorticoids when patients with asthma or COPD have severe exacerbations. Biologics such as benralizumab can effectively treat patients with high blood eosinophil counts.

Indeed, researchers at the University of Oxford have found that a single 100 mg subcutaneous injection of benralizumab can reduce exacerbations and readmissions for at least 90 days in patients with eosinophilic inflammation. High-dose benralizumab reduced the odds of treatment failing by 74% compared with the usual steroid burst.

“This is a game changer, a paradigm shift in how we think about treating exacerbations,” said Dharani K. Narendra, MD, FCCP, Assistant Professor of Pulmonary, Critical Care, and Sleep Medicine at Baylor College of Medicine and a member of the CHEST Physician Editorial Board. “It will change our treatment strategies and focus on personalized medicine. It may no longer be one-size-fits-all when we are treating exacerbations.”

Benralizumab and other biologics have dramatically reduced the incidence of exacerbations for patients with asthma, if not yet in COPD, Dr. Narendra noted. But not all patients who could benefit from biologics get them, and not all biologics are 100% effective in preventing exacerbations for all patients. Patient individualization and drug selection are key.

The only approach to treat severe exacerbations has long been systemic steroids and perhaps antibiotics. Then came case reports of patients for whom glucocorticoids were contraindicated but who found relief from benralizumab. All had eosinophilic inflammation.

The phase 2 Acute exacerbations treated with BenRAlizumab (ABRA) trial compared a single 100 mg dose of benralizumab with standard of care prednisone 30 g/daily for five days. Patients were recruited from hospital urgent care and emergency departments in the United Kingdom. All had acute exacerbations of asthma or COPD, and all had blood eosinophil counts of at least 300 cells/μl.

The trial included 158 patients, with 53 randomized to prednisone, 53 to benralizumab, and 52 to prednisone plus benralizumab. Just more than half the population (54%) was female, with a mean age of 57 and a mean of four exacerbations yearly. About half the patients (56%) had asthma, 32% had COPD, and 12% had mixed asthma and COPD. Virtually all were on inhalation therapy and typically some combination of glucocorticoids (99%), long-acting bronchodilators (97%), or long-acting antimuscarinics (46%).

At 90 days, 74% of the prednisone group had experienced treatment failure, defined as death, hospitalization, or need for retreatment with systemic glucocorticoids or antibiotics, vs 45% for the pooled benralizumab groups.

There were no fatal adverse events, and benralizumab was well tolerated. Hyperglycemia and sinusitis or sinus infection were associated only with prednisone.

“The main aim with biologics has always been to prevent exacerbations in asthma and COPD,” Dr. Narendra said. “This is the first-ever study to look at a precision medicine target-specific population with high eosinophilic inflammation during an exacerbation. It’s the first time we may have found an alternative to steroids. Even one or two courses of systemic steroids can have dramatic side effects. Patients with recurrent exacerbations require more steroids, and the side effects compound.”

There are two dominant patterns of airway inflammation in acute exacerbations: infection-associated neutrophilic airway inflammation and noninfection-associated eosinophilic airway inflammation. Both are seen in asthma and COPD and can be distinguished only through blood eosinophil count.

Benralizumab depletes eosinophils quickly and is the longest-acting biologic that has been shown to reduce exacerbations in patients with asthma. Dr. Narendra said it is almost always used in the outpatient setting, typically by self-injection.

“Getting benralizumab for patients with exacerbations is challenging right now with insurance approval and cost,” she said. “I’m not sure if we can start it as routine practice, as we need larger trials to show similar benefit in this subset of patients with high eosinophils and frequent exacerbations. If further studies confirm these findings, benralizumab could become a first-line treatment option for eosinophilic exacerbations, leading to changes in asthma and COPD management guidelines. If we can prevent one future exacerbation, that is highly beneficial for the patient, the hospital, and the health care system.”