Stepping Up to Asthma Care: New Biologics and Multidisciplinary Management Offer the Prospect of Better Control

By Kartik Shenoy, MD

Benralizumab binds to eosinophils, inhibiting binding of IL-5 and inducing apoptosis.

Only 3 to 10 percent of asthma cases are considered severe or difficult to control, yet those cases are responsible for more than 60 percent of asthma expenditures.1 Over the last few years, options for patients with severe asthma have both improved and become a great deal more complex for physicians due to the advent of personalized medicine and enhanced understanding of the disease. New biologic therapies may help those with truly resistant asthma, but due to their cost, physicians should first consider optimizing standard-of-care therapies and treating comorbidities that may be exacerbating the disease. A multidisciplinary differential diagnosis process can help identify the treatments most likely to be effective and affordable.

Addressing treatment adherence and proper inhaler use results in improvement for a substantial proportion of patients who at first appeared to have uncontrollable asthma.2 A multidisciplinary specialist team can then help pinpoint other important factors—for example, uncontrolled sleep apnea, gastrointestinal disorders, and unrecognized allergies—that may be worsening the patient’s symptoms. Some patients may not even have asthma at all—upper airway issues like laryngeal spasms may mimic asthma attacks, and can be diagnosed and treated by ear, nose and throat physicians. A team treatment paradigm, employed at specialty centers like Temple, may help patients avoid costlier treatments and improve their overall health by bringing in specialists from multiple fields to help improve asthma care. It also helps identify patients who do require additional advanced interventions like biologics, bronchial thermoplasty or clinical trials.

Biologic therapies for asthma continue to evolve, especially for TH2-high asthma (characterized by high type 2 T-helper-cell activity, high eosinophil levels in bodily fluids and elevated IgE levels, sometimes accompanied by allergic symptoms or positive allergy tests). Patients with severe TH2-high asthma were, until recently, reliant solely on Xolair® (omalizumab), an anti-IgE agent to which some did not respond. Lately, researchers have found that targeting the eosinophil and interleukin-5 (IL-5) pathways may help reduce exacerbations and improve the condition of patients whose symptoms do not improve with standard treatments. In recent years, mepolizumab (Nucala®), reslizumab (Cinqair®) and benralizumab (Fasenra®), have come onto the market, targeting the IL-5 pathway. All three have been shown to reduce asthma exacerbations and improve asthma quality of life. Both benralizumab and reslizumab additionally have shown mild improvement in lung function.3,4

There are yet other patients with TH2-high asthma who do not respond to any FDA-approved biologic treatments. New research is exploring pathways a step or two above the IL-5 pathway, which may tackle multiple disease mechanisms and have potential for broader impact. In a Phase 2 trial of a few hundred patients, subcutaneous tezepelumab decreased asthma exacerbation rates by an average of 61 to 71 percent (depending on dosage), regardless of the patient’s blood eosinophil level. Patients receiving tezepelumab also performed better in tests of forced expiratory volume.5 Temple will soon be enrolling patients who are steroid-dependent asthmatics for a Phase 3 trial of tezepelumab called the SOURCE trial (ClinicalTrials.gov Identifier: NCT03406078).

Finally, some asthma patients may be eligible for bronchial thermoplasty, in which radiofrequency energy is used to ablate smooth muscle in the airway wall, reducing asthma attacks and improving quality of life in people with difficult-to-control asthma. Temple was the first in the Philadelphia region to offer this technique commercially. With continued research into biologics, we will see improved personalized medical therapy for asthma soon. By combining innovative treatments with comprehensive, multidisciplinary care, we can bring relief to patients who had thought their condition unmanageable.


References

1 Israel, E.I., and Reddel, H.K. (2017). Severe and Difficult-to-Treat Asthma in Adults. N Engl J Med. 377 (10): 965–976.
2 Israel and Reddel 2017.
3 Cinqair [package insert]. (2016). Teva Respiratory LLC, Frazer, PA.
4 Ferguson, G.T., et al. (2017). Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 5 (7): 568–576. doi: 10.1016/S2213-2600(17)30190-X.
5 Corren, J., et al. (2017). Tezepelumab in Adults with Uncontrolled Asthma. N Engl J Med. 377 (10): 936–946.