The FDA approved omalizumab (Xolair) in 2003 to treat patients with asthma and an elevated IgE level. Recently, the FDA approved mepolizumab (brand name Nucala) as a treatment for patients with asthma. Nucala was approved for patients aged 12 and above as add-on maintenance therapy for severe asthma with an eosinophilic phenotype.
Mepolizumab is a humanized interleukin 5 antagonist monoclonal antibody. IL-5 is the major cytokine responsible for the growth and differentiation (as well as recruitment and activation) of eosinophils. The only approved dosage is 100 mg subcutaneously every 4 weeks. Because of the possibility of a hypersensitivity reaction, it should be administered in a health care setting appropriate for biological agents. The most commonly reported manifestations of hypersensitivity reactions in the clinical trials of Nucala have included rash, angioedema, bronchospasm, hypotension and urticaria. However the rates of these reactions were comparable to the placebo group.
Because eosinophils are involved in the immune response to helminthic infections, it is recommended to treat such an infection before starting mepolizumab therapy, and to consider discontinuation of therapy if such an infection occurs while a patient is on Nucala. Two patients in the mepolizumab clinical trials experienced serious adverse reactions of herpes zoster (versus none in the placebo group); therefore varicella-zoster vaccination should be considered prior to starting Nucala therapy. Injection site reactions (such as pain, swelling, itching or burning) occurred in 8% of the mepolizumab group versus 3% of the placebo group.
A total of 1,327 subjects with asthma were included in three randomized, placebo controlled multicenter studies of 24 to 52 weeks duration. The vast majority (1,192) of these patients had two or more asthma exacerbations in the 12 months prior to study enrollment despite being on high dose inhaled corticosteroids plus an additional controller therapy (which could include a long acting beta agonist, a leukotriene receptor antagonist, or theophylline). 135 of the subjects actually required daily oral corticosteroids in addition to using high dose inhaled steroids and an additional controller medication. The patients were required to have blood eosinophil levels of at least 150 cells/mcL within 6 weeks of dosing OR at least 300 cells/mcL within 12 months of enrollment.
The patients who received mepolizumab in the clinical trials had significantly less exacerbations (approximately 47% less) and a significantly lower exposure to systemic steroids. There were also fewer exacerbations requiring hospitalization and/or emergency department visits in the mepolizumab group versus placebo. In some studies, the FEV1 improved by about 100 ml on mepolizumab. In the patients who were on maintenance oral steroids there was a significant decrease in their dose requirement overall with mepolizumab. The likelihood of a reduction of the glucocorticoid dose was 2.39 times greater in the mepolizumab group (95% Cl 1.25-4.56) and the mean reduction from baseline was 50 percent compared with no reduction in the placebo group.
It is interesting to note that only about 30% of subjects enrolled in the mepolizumab studies met the prescribing criteria for omalizumab. Therapy such as omalizumab directed against IgE for asthma has not been evaluated in “non-allergic” patients. Asthma can be characterized as “allergic” and “non-allergic”. Allergic asthmatic patients are, in general, younger and have a better response to therapy. Non-allergic asthmatic patients are often adult onset and this is associated with non-allergic co-morbidities, such as rhinosinusitis and gastro-esophageal reflux and does not respond as well to therapy. The use of other currently available asthma treatments does not distinguish between allergic and non-allergic patients. At this point, there is no data regarding concomitant use of mepolizumab and omalizumab. As the science of asthma therapy advances, clinicians will need to learn more about the different asthma phenotypes and their response to these targeted therapies.
By Daniel T. Layish, MD, FACP, FCCP, FAASM
Daniel Layish, MD, graduated magna cum laude from Boston University Medical School in 1990. He then completed an Internal Medicine Residency at Barnes Hospital (Washington University) in St.Louis, Missouri and a Pulmonary/Critical Care/Sleep Medicine Fellowship at Duke University in Durham, North Carolina. Since 1997, he has been a member of the Central Florida Pulmonary Group in Orlando. He serves as Co-director of the Adult Cystic Fibrosis Program in Orlando. He may be contacted at 407-841-1100 or by visiting CFPulmonary.com.