Efficacy of soluble IL-4 receptor for the treatment of adults with asthma.
BACKGROUND
IL-4 mediates important proinflammatory functions in asthma, including induction of the IgE isotype switch, increased expression of vascular cell adhesion molecule 1 and promotion of eosinophil transmigration across the endothelium, stimulation of mucus production, and T(H)2 lymphocyte differentiation, leading to release of IL-4, IL-5, IL-9, and IL-13.


OBJECTIVE
The current study evaluated the therapeutic potential of inhaled recombinant human soluble interleukin-4 receptor (IL-4R) as an IL-4 antagonist.


METHODS
This study was a randomized, double-blind, placebo-controlled study in 62 subjects involving 12 once weekly nebulizations of 0.75, 1.5, or 3.0 mg of IL-4R or placebo. During screening, subjects documented dependence on inhaled corticosteroids by an exacerbation in asthma induced by one or two 50% dose reductions at 2-week intervals. After restabilization for 2 weeks on the dose above which their asthma flared, inhaled steroids were discontinued, patients were randomized, and study medication was started on day 0.


RESULTS
IL-4R was well tolerated. Efficacy was demonstrated by a decline in FEV(1) observed in the placebo group (-0.4 L and -13% predicted), which did not occur in the group receiving 3.0 mg of IL-4R (-0.1 L and -2% predicted; P =.05 over the 3-month treatment period). Daily patient-measured morning FEV(1) also demonstrated a significant decline in the placebo group (-0.5 L and -18% predicted), which did not occur in the group receiving 3.0 mg of IL-4R (-0.1 L and -4% predicted; P =.02 over the 3-month treatment period). The efficacy of IL-4R was further confirmed by the absence of increase in asthma symptom scores in the group receiving 3.0 mg of IL-4R (Delta 0.1) compared with that seen in the placebo group (Delta 1.4 over 1 month; P =.07). Study discontinuation for asthma exacerbation was not significantly different between groups (placebo, 56%; 3.0 mg of IL-4R, 47%; P = not significant).


CONCLUSIONS
These promising data suggest that IL-4R is safe and effective in the treatment of moderate persistent asthma.
Borish
L C
LC
National Jewish Medical and Research Center, University of Colorado, Health Sciences Center, Denver, CO, USA.
Nelson
H S
HS
Corren
J
J
Bensch
G
G
Busse
W W
WW
Whitmore
J B
JB
Agosti
J M
JM
D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D019948:Receptors, Interleukin-4 / Q000097:blood / Q000235:genetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012995:Solubility
D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D015847:Interleukin-4