Interleukin-4 Receptor in Moderate Atopic Asthma

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Abstract
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 μ g, IL-4R 500 μ g, or placebo after stopping inhaled corticosteroids. No drug-related toxicity was observed. Treatment with IL-4R produced significant improvement in FEV1 on Day 4 (1,500 μ g versus placebo; p < 0.05) and in FEF25–75 on Days 2 and 4 (1,500 μ g versus placebo; p < 0.05). Asthma symptom scores stabilized among patients treated with IL-4R 1,500 μ g, despite abrupt withdrawal of corticosteroids, but not in the IL-4R 500 μ g group or the placebo group (p < 0.05). Patients in the IL-4R 1,500 μ g group also required significantly less β2-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 μ g dose appears as safe but significantly more effective than the 500 μ g dose. Borish LC, Nelson HS, Lanz MJ, Claussen L, Whitmore JB, Agosti JM, Garrison L. Interleukin-4 receptor in moderate atopic asthma: a phase I/II randomized, placebo-controlled trial.

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