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


CONCLUSIONS
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.
Borish
L C
LC
Department of Medicine, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, Colorado 80206, USA. BorishL@NJC.org
Nelson
H S
HS
Lanz
M J
MJ
Claussen
L
L
Whitmore
J B
JB
Agosti
J M
JM
Garrison
L
L
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications*; D007073:Immunoglobulin E / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008450:Maximal Midexpiratory Flow Rate; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010366:Peak Expiratory Flow Rate; D011788:Quality of Life; D019948:Receptors, Interleukin-4 / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007073:Immunoglobulin E