The investigational humanized monoclonal antibody mepolizumab had a significant glucocorticoid-sparing effect in patients with severe eosinophilic asthma, researchers report.
Severe asthma patients who added mepolizumab to their maintenance dose of oral glucocorticoids were 2.39 times more likely to tolerate a reduction in glucocorticoid dosage, compared with the placebo group (95% confidence interval, 1.25-4.56; P = .008), Dr. Elisabeth H. Bel and her colleagues from the University of Amsterdam’s department of respiratory medicine found.
The findings of their industry-sponsored Steroid Reduction with Mepolizumab (SIRIUS) study were presented at the annual congress of the European Respiratory Society and published simultaneously in the New England Journal of Medicine.
The phase III trial included 135 adults with severe asthma who had at least a 6-month history of glucocorticoid treatment. Eosinophilic inflammation was defined as a blood eosinophil level of 300 cells/mcL or more before the study, or 150 cells/mcL or more during the optimization phase (doi: 10.1056/NEJMoa1403291).
In the first of four phases, glucocorticoid use was reduced weekly to establish the lowest dose needed to maintain asthma control. In the induction phase, patients were randomized to receive either a 100-mg dose of mepolizumab or placebo, in addition to their optimized glucocorticoid dose. Then, in the reduction phase (weeks 4 to 20), this glucocorticoid dose was gradually reduced by 1.25-10 mg per day every 4 weeks, based on asthma control and adrenal insufficiency. Finally, in the maintenance phase (weeks 20-24), no additional modifications were made to the glucocorticoid dose, and a follow-up safety visit was scheduled. Patients used an electronic diary to record data on peak expiratory flow, asthma symptoms, and scores on the Asthma Control Questionnaire 5 (ACQ-5).
Efficacy was measured by the percentage reduction in daily oral glucocorticoid dose during the maintenance phase, compared with the optimized dose in the first phase.
The primary analysis showed that 23% of patients in the mepolizumab group had a glucocorticoid dose reduction of 90%-100%, compared with just 11% of patients in the placebo group. Additionally, 17% of mepolizumab patients saw a reduction of 70% to less than 90%, compared with 8% of placebo patients. A total of 56% of patients in the placebo group had no reduction in glucocorticoid dose, showed a lack of asthma control, or pulled out of the trial, versus 36% of patients in the mepolizumab group.
Because the use of oral glucocorticoid treatment can lead to serious adverse effects, many patients with severe eosinophilic asthma may take lower doses than is needed to adequately maintain symptom control, the investigators said in the report. The results of this study suggest that adding mepolizumab to this regimen may be a viable option to allow for use of lower glucocorticoid doses in these patients while still achieving symptom control and mitigating severe complications, they added.
Mepolizumab is not currently approved anywhere in the world.
Among potential limitations of their small study, the authors wrote, was that they "assumed a relationship between a worsening of symptoms and an increase in eosinophilic airway inflammation, which may not be valid for all patients. It is possible that if we had mandated evidence of eosinophilic inflammation in the optimization phase, a different drug effect would have been seen."
Several researchers disclosed financial relationships with industry firms, including mepolizumab developer GlaxoSmithKline, the sponsor and designer of the study.
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