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FDA has approved mepolizumab for adjunctive maintenance treatment of severe asthma in patients 12 years of age and older with markers of eosinophilic asthma.
Kathryn WheelerOn November 4, 2015, mepolizumab (Nucala; GlaxoSmithKline, Inc.) was approved by FDA for adjunctive maintenance treatment of severe asthma in patients 12 years of age and older with markers of eosinophilic asthma.
Mepolizumab is a humanized interleukin-5 antagonist monoclonal antibody. It binds and inhibits the activity of interleukin-5, which is essential to the proper development, activation, and survival of eosinophils.
Eosinophils contribute significantly to the inflammatory pathology of asthma in some patients, resulting in an eosinophilic phenotype. Use of mepolimumab in patients with eosinophilic asthma can decrease severe asthma attacks.
FDA based its approval of mepolizumab as adjunctive therapy for eosinophilic asthma on three randomized double-blind placebo-controlled trials. In all trials, mepolizumab was administered monthly as add-on therapy to appropriate maintenance treatments for asthma control.
The first trial determined an appropriate dose range and assessed impact of mepolizumab on frequency of exacerbations.
A second trial also assessed the impact of mepolizumab on exacerbations in patients with a history of two or more exacerbations within the previous year despite maximized inhaled corticosteroid maintenance therapy and blood eosinophil counts ≥ 150 cells/mcL within six weeks of the patient’s receiving a dose of trial medication, or a blood eosinophil count ≥300 cells/mcL within the previous year.
An exacerbation was defined as a need for systemic corticosteroids, a hospitalization, or an emergency department visit. In these trials, participants receiving mepolizumab experienced significantly fewer exacerbations compared to participants receiving placebo.
Of note, the participants with historical eosinophil counts of≤300 cells/mcL within the previous year but who also had blood eosinophil counts of ≤150 cells/mcL within the previous six weeks, did not demonstrate similar benefit of exacerbation reduction despite receiving mepolizumab.
A third trial assessed the effect of meoplizumab 100 mg on corticosteroid use in participants with blood eosinophil counts of 150 cells/mcL or more within the previous six weeks, who required daily oral corticosteroid doses in addition to maximized asthma control therapy including high-dose inhaled corticosteroids.
The primary endpoint of this trial was the percent reduction of oral steroid dose during weeks 20 through 24 compared to the baseline dose while control of asthma symptoms was also maintained.
Participants receiving mepolizumab demonstrated greater reductions in oral steroid doses compared to those receiving placebo.
None of the trials demonstrated an improvement in lung function with use of mepolizumab.
In trials, the adverse effects most commonly associated with mepolizumab included headache, back pain, fatigue, and injection-site reactions.
Allergic reactions including angioedema, bronchospasm, hives, rash, and hypotension have occurred with use of mepolizumab. Reactions may occur within hours to days of administration.
Herpes zoster infections have occurred in patients administered mepolizumab. If medically appropriate, varicella vaccination should be considered.
Mepolizumab may interfere with immunological response to helminth infections. Patients with helminth infections should be treated prior to initiation of mepolizumab. Patients infected while on mepolizumab and not responding to anti-helminthic treatment should discontinue mepolizumab until the infection resolves.
Mepolizumab is not intended for treatment of acute bronchospasm.
Mepolizumab is administered as a 100-mg dose by subcutaneous injection once every four weeks. It may be administered in the thigh, abdomen, or upper arm.
The vial of Nucala must be reconstituted with 1.2 mL of sterile water for injection to achieve a final concentration of 100 mg/mL of mepolizumab. Do not shake the vial, as this can result in foaming or precipitation of the product.
There are limited data on use of mepolizumab in patients with renal or hepatic impairment. However, mepolizumab is not renally eliminated and is degraded by enzymes not limited to the liver.
Corticosteroids should not be abruptly discontinued with initiation of mepolizumab. If appropriate, the corticosteroid dose may be gradually decreased.
Kathryn Wheeleris associate clinical professor, Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Conn.