Nasal IL-5 levels determine the response to anti–IL-5 treatment in patients with nasal polyps

• Published in: Journal of Allergy and Clinical Immunology 2006-11, Vol.118 (5), p.1133-1141
• Main Authors: Gevaert, Philippe, Lang-Loidolt, Doris, Lackner, Andreas, Stammberger, Heinz, Staudinger, Heribert, Van Zele, Thibaut, Holtappels, Gabriele, Tavernier, Jan, van Cauwenberge, Paul, Bachert, Claus
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; anti–IL-5; Biological and medical sciences; Chronic rhinosinusitis; Clinical trials; Double-Blind Method; Drug therapy; eosinophils; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; IL-5; IL-5 receptor α; Immunopathology; Injections, Intravenous; Interleukin-5 - antagonists & inhibitors; Interleukin-5 - biosynthesis; Interleukin-5 - immunology; Interleukin-5 - metabolism; Male; Medical sciences; Middle Aged; Nasal Mucosa - immunology; Nasal Mucosa - metabolism; nasal polyps; Nasal Polyps - immunology; Nasal Polyps - metabolism; Nasal Polyps - therapy; Otolaryngology; Surgery
• ISSN: 0091-6749; 1097-6825; 1365-2567
• DOI: 10.1016/j.jaci.2006.05.031

Chronic rhinosinusitis with nasal polyps is characterized by an eosinophilic inflammation and high IL-5 levels. Antagonizing the effect of IL-5 is a potential new treatment strategy in patients with nasal polyps. In a double-blind, placebo-controlled, randomized, 2-center safety and pharmacokinetic study, 24 subjects with bilateral nasal polyps were randomized to receive a single intravenous infusion of reslizumab, a humanized anti-human IL-5 mAb, at 3 mg/kg or 1 mg/kg or placebo. We evaluated the safety and pharmacokinetics of reslizumab, and biologic activity was assessed by means of endoscopic evaluation of polyp size, symptoms, peripheral eosinophil counts, peripheral and local IL-5 levels, eotaxin levels, and eosinophil cationic protein levels. We demonstrated that a single injection of reslizumab up to 3 mg/kg is safe and well tolerated. Blood eosinophil numbers and concentrations of eosinophil cationic protein were reduced up to 8 weeks after treatment in serum and nasal secretions. Individual nasal polyp scores improved only in half of the treated patients for 4 weeks. Responders had increased IL-5 concentrations in nasal secretions at baseline compared with nonresponders, and logistic regression analysis revealed that increased nasal IL-5 levels (>40 pg/mL) predict the response to anti-IL-5 treatment. A single injection of anti–IL-5 reduces the size of nasal polyps for 4 weeks in half of the patients, and nasal IL-5 levels predict the response to anti–IL-5 treatment. Intravenous administration of a humanized anti-human IL-5 mAb is safe and reduces the size of nasal polyps in half of the patients.