Efficacy of soluble IL-4 receptor for the treatment of adults with asthma.

Abstract

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).

CONCLUSION:

These promising data suggest that IL-4R is safe and effective in the treatment of moderate persistent asthma.

• Authors: L C Borish, H S Nelson, J Corren, G Bensch, W W Busse, J B Whitmore, J M Agosti, IL-4R Asthma Study Group
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 107 Issue 6 Pg. 963-70 (Jun 2001) ISSN: 0091-6749 [Print] United States
• PMID: 11398072 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Receptors, Interleukin-4
• Recombinant Proteins
• Interleukin-4

Topics

• Adult
• Aged
• Asthma (drug therapy)
• Double-Blind Method
• Female
• Forced Expiratory Volume
• Humans
• Interleukin-4 (antagonists & inhibitors, metabolism)
• Male
• Middle Aged
• Nebulizers and Vaporizers
• Receptors, Interleukin-4 (blood, genetics, therapeutic use)
• Recombinant Proteins (therapeutic use)
• Solubility