A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma.
BACKGROUND
Accumulation of eosinophils in the bronchial mucosa of individuals with asthma is considered to be a central event in the pathogenesis of asthma. In animal models, airway eosinophil recruitment and airway hyperresponsiveness in response to allergen challenge are reduced by specific targeting of interleukin-5. A previous small dose-finding study found that mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, had no effect on allergen challenge in humans.


OBJECTIVE
To investigate the effect of three intravenous infusions of mepolizumab, 250 or 750 mg at monthly intervals, on clinical outcome measures in 362 patients with asthma experiencing persistent symptoms despite inhaled corticosteroid therapy (400-1,000 mug of beclomethasone or equivalent).


METHODS
Multicenter, randomized, double-blind, placebo-controlled study.


RESULTS
Morning peak expiratory flow, forced expiratory volume in 1 second, daily beta(2)-agonist use, symptom scores, exacerbation rates, and quality of life measures. Sputum eosinophil levels were also measured in a subgroup of 37 individuals. Mepolizumab was associated with a significant reduction in blood and sputum eosinophils in both treatment groups (blood, P < 0.001 for both doses; sputum, P = 0.006 for 250 mg and P = 0.004 for 750 mg). There were no statistically significant changes in any of the clinical end points measured. There was a nonsignificant trend for decrease in exacerbation rates in the mepolizumab 750-mg treatment group (P = 0.065).


CONCLUSIONS
Mepolizumab treatment does not appear to add significant clinical benefit in patients with asthma with persistent symptoms despite inhaled corticosteroid therapy. Further studies are needed to investigate the effect of mepolizumab on exacerbation rates, using protocols specifically tailored to patients with asthma with persistent airway eosinophilia.
Flood-Page
Patrick
P
F.R.C.P., London Chest Hospital, Bonner Road, London E2 9JX, UK.
Swenson
Cheri
C
Faiferman
Isidore
I
Matthews
John
J
Williams
Michael
M
Brannick
Lesley
L
Robinson
Douglas
D
Wenzel
Sally
S
Busse
William
W
Hansel
Trevor T
TT
Barnes
Neil C
NC
D000280:Administration, Inhalation; D000322:Adrenergic Agonists / Q000627:therapeutic use; D058666:Adrenergic beta-2 Receptor Agonists; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D001507:Beclomethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D011788:Quality of Life; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology; D017211:Treatment Failure
D000322:Adrenergic Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C434107:mepolizumab; D001507:Beclomethasone