title: Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study.
abstract: Antagonizing the effect of interleukin (IL)-5 is a potential new treatment strategy in allergic disorders. We evaluated the safety, biological activity, and pharmacokinetics of SCH55700, a humanized anti-human IL-5 antibody, in subjects with severe persistent asthma treated with oral or high doses of inhaled steroids. In a double-blind, randomized, multicenter trial, a rising single dose of SCH55700 (0.03 mg/kg [n = 2], 0.1 mg/kg [n = 4], 0.3 mg/kg [n = 6], or 1.0 mg/kg [n = 12]) or placebo (n = 8) was administered intravenously. SCH55700 dose dependently reduced circulating eosinophil counts. At a dose of 1.0 mg/kg, the decrease remained significant up to Day 30 [(0.07 +/- 0.01) x 10(9)/L versus (0.23 +/- 0.04) x 10(9)/L at baseline] (mean +/- SEM) (p = 0.05). After administration of SCH55700 at 0.3 and 1.0 mg/kg, a trend toward improvement in baseline FEV1 was observed, which reached significance 24 hours after the 0.3-mg/kg dose (p = 0.019 versus placebo). No significant changes occurred in other clinical indices of disease activity. Adverse events were not different between active treatment and placebo. We conclude that SCH55700 is a biologically active anti-human IL-5 antibody that can be safely used in severe steroid-treated asthma. Its therapeutic potential needs to be addressed in specifically designed efficacy trials.
authors.affiliation: Department of Respiratory Diseases, Ghent University Hospital, De Pintelaan 185, B 9000 Ghent, Belgium. johan.kips@rug.ac.be
authors.forename: Johan C
authors.initials: JC
authors.lastname: Kips
authors.forename: Brian J
authors.initials: BJ
authors.lastname: O'Connor
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Langley
authors.forename: Ashley
authors.initials: A
authors.lastname: Woodcock
authors.forename: Huib A M
authors.initials: HA
authors.lastname: Kerstjens
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Mel
authors.initials: M
authors.lastname: Danzig
authors.forename: Francis
authors.initials: F
authors.lastname: Cuss
authors.forename: Romain A
authors.initials: RA
authors.lastname: Pauwels
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D018927:Anti-Asthmatic Agents / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D016903:Drug Monitoring; D004802:Eosinophilia / Q000097:blood / Q000209:etiology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D010865:Pilot Projects; D012449:Safety; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018927:Anti-Asthmatic Agents; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015848:Interleukin-5