Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps.
BACKGROUND
Chronic rhinosinusitis with nasal polyps is characterized by an eosinophilic inflammation and high IL-5 levels.


OBJECTIVE
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.


CONCLUSIONS
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.


CONCLUSIONS
Intravenous administration of a humanized anti-human IL-5 mAb is safe and reduces the size of nasal polyps in half of the patients.
Gevaert
Philippe
P
Upper airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium. philippe.gevaert@UGent.be <philippe.gevaert@UGent.be>
Lang-Loidolt
Doris
D
Lackner
Andreas
A
Stammberger
Heinz
H
Staudinger
Heribert
H
Van Zele
Thibaut
T
Holtappels
Gabriele
G
Tavernier
Jan
J
van Cauwenberge
Paul
P
Bachert
Claus
C
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism*; D009298:Nasal Polyps / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015848:Interleukin-5; C515492:reslizumab