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

Gevaert, Philippe MD, PhD
Lang-Loidolt, Doris MD
Lackner, Andreas MD
Stammberger, Heinz MD
Staudinger, Heribert MD, PhD
Van Zele, Thibaut MD
Holtappels, Gabriele
Tavernier, Jan PhD
van Cauwenberge, Paul MD, PhD
Bachert, Claus MD, PhD

^aUpper airways Research Laboratory, Ghent, Belgium
^dDepartment of Medical Protein Research, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium
^bDepartment of Otorhinolaryngology, University Medical School, Graz, Austria
^cSchering-Plough Research Institute, Kenilworth, NJ

Reprint requests: Philippe Gevaert, MD, PhD, Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium. E-mail: [email protected].

Supported by Schering-Plough Research Institute, Kenilworth, NJ.

Disclosure of potential conflict of interest: H. Staudinger is employed by and owns stock in Schering-Plough Corp. The rest of the authors have declared that they have no conflict of interest.

Received for publication November 29, 2005; revised May 3, 2006; accepted for publication May 24, 2006. Available online September 28, 2006.

Journal of Allergy & Clinical Immunology 118(5):p 1133-1141, November 2006.

Background

Chronic rhinosinusitis with nasal polyps is characterized by an eosinophilic inflammation and high IL-5 levels.

Objectives

Antagonizing the effect of IL-5 is a potential new treatment strategy in patients with nasal polyps.

Methods

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.

Results

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.

Conclusion

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.

Clinical implications

Intravenous administration of a humanized anti-human IL-5 mAb is safe and reduces the size of nasal polyps in half of the patients.