Interleukin-4 receptor in moderate atopic asthma: A phase I/II randomized, placebo-controlled trial

• Published in: American journal of respiratory and critical care medicine 1999-12, Vol.160 (6), p.1816-1823
• Main Authors: BORISH, L. C, NELSON, H. S, LANZ, M. J, CLAUSSEN, L, WHITMORE, J. B, AGOSTI, J. M, GARRISON, L
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adult; Aged; Asthma - drug therapy; Asthma - immunology; Asthma - physiopathology; Biological and medical sciences; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hypersensitivity, Immediate - complications; Immunoglobulin E - blood; Intercellular Adhesion Molecule-1 - blood; Male; Maximal Midexpiratory Flow Rate; Medical sciences; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Pharmacology. Drug treatments; Quality of Life; Receptors, Interleukin-4 - administration & dosage; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Respiratory system; Vascular Cell Adhesion Molecule-1 - blood
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.160.6.9808146

Interleukin-4 mediates important proinflammatory functions in asthma, including induction of the IgE isotype switch, expression of VCAM-1 on endothelium, mucin production, 15-lipoxygenase activity, and Th2 lymphocyte stimulation leading to the secondary synthesis of IL-4, IL-5, and IL-13. Soluble recombinant human IL-4 receptor (IL-4R; Nuvance; altrakincept) inactivates naturally occurring IL-4 without mediating cellular activation. Nebulized IL-4R has a serum half-life of approximately 1 wk. In this double-blind, placebo-controlled trial, 25 patients with moderate asthma requiring inhaled corticosteroids were randomly assigned to receive a single nebulized dose of IL-4R 1,500 microg, IL-4R 500 microg, or placebo after stopping inhaled corticosteroids. No drug-related toxicity was observed. Treatment with IL-4R produced significant improvement in FEV(1) on Day 4 (1,500 microg versus placebo; p < 0.05) and in FEF(25-75) on Days 2 and 4 (1,500 microg versus placebo; p < 0.05). Asthma symptom scores stabilized among patients treated with IL-4R 1, 500 microg, despite abrupt withdrawal of corticosteroids, but not in the IL-4R 500 microg group or the placebo group (p < 0.05). Patients in the IL-4R 1,500 microg group also required significantly less beta(2)-agonist rescue use (p < 0.05). Anti-inflammatory effects were further demonstrated by significantly reduced exhaled nitric oxide (p < 0.05). A single dose of IL-4R appears safe and effective in moderate asthma. The 1,500 microg dose appears as safe but significantly more effective than the 500 microg dose.