Omalizumab for Aspirin Hypersensitivity and Leukotriene Overproduction in Aspirin-exacerbated Respiratory Disease. A Randomized Controlled Trial

Abstract

Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, non-steroidal anti-inflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic corticosteroid therapy does not completely suppress lifelong aspirin-hypersensitivity. Omalizumab efficacy against aspirin-exacerbated respiratory disease has not been investigated in a randomized manner. Objectives: To evaluate omalizumab efficacy against aspirin-hypersensitivity, leukotriene E₄ overproduction, and symptoms during oral aspirin challenge in aspirin-exacerbated respiratory disease using a randomized design. Methods: We performed a double-blind, randomized, cross-over, placebo-controlled, single-centre study at Sagamihara National Hospital between August 2015 and December 2016. Atopic patients aged 20–79 years with aspirin-exacerbated respiratory disease diagnosed by systemic aspirin challenge were randomized (1:1) to 3-month treatment with omalizumab or placebo, followed by >18-week washout period (cross-over design). The primary endpoint was the difference in area under logarithm level of urinary leukotriene E₄ concentration vs time curve in the intention-to-treat population during oral aspirin challenge. Measurements and Main Results: Sixteen patients completed the study and were included in the analysis. The area under the logarithm level of urinary leukotriene E₄ concentration vs time curve during oral aspirin challenge in the omalizumab phase (median [interquartile range], 51.1 [44.5–59.8]) was significantly lower compared with the placebo phase (80.8 [interquartile range, 65.4–87.8]) (p4 overproduction and upper/lower respiratory tract symptoms during oral aspirin challenge, resulting in aspirin tolerance in 62.5% of aspirin-exacerbated respiratory disease patients. Clinical trial registration available at https://www.umin.ac.jp/ctr/index.htm, ID: UMIN000018777.