Omalizumab for aspirin hypersensitivity and leukotriene overproduction in aspirin-exacerbated respiratory disease

Hiroaki Hayashi, Yuma Fukutomi, Chihiro Mitsui, Keiichi Kajiwara, Kentaro Watai, Yosuke Kamide, Yuto Nakamura, Yuto Hamada, Yasuhiro Tomita, Kiyoshi Sekiya, Takahiro Tsuburai, Kenji Izuhara, Keiko Wakahara, Naozumi Hashimoto, Yoshinori Hasegawa, Masami Taniguchi

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

Abstract

Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, nonsteroidal antiinflammatory 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 an oral aspirin challenge in patients with aspirin-exacerbated respiratory disease using a randomized design. Methods: We performed a double-blind, randomized, crossover, placebo-controlled, single-center study at Sagamihara National Hospital between August 2015 and December 2016. Atopic patients (20–79 yr old) with aspirin-exacerbated respiratory disease diagnosed by systemic aspirin challenge were randomized (1:1) to a 3-month treatment with omalizumab or placebo, followed by a .18-week washout period (crossover design). The primary endpoint was the difference in area under logarithm level of urinary leukotriene E4 concentration versus time curve in the intent-to-treat population during an 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 versus time curve during an oral aspirin challenge was significantly lower in the omalizumab phase (median [interquartile range], 51.1 [44.5–59.8]) than in the placebo phase (80.8 [interquartile range, 65.4–87.8]) (P, 0.001). Ten of 16 patients (62.5%) developed oral aspirin tolerance up to cumulative doses of 930 mg in the omalizumab phase (P, 0.001). Conclusions: Omalizumab treatment inhibited urinary leukotriene E4 overproduction and upper/lower respiratory tract symptoms during an oral aspirin challenge, resulting in aspirin tolerance in 62.5% of the patients with aspirin-exacerbated respiratory disease.

Original languageEnglish
Pages (from-to)1488-1498
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume201
Issue number12
DOIs
Publication statusPublished - 15-06-2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Fingerprint

Dive into the research topics of 'Omalizumab for aspirin hypersensitivity and leukotriene overproduction in aspirin-exacerbated respiratory disease'. Together they form a unique fingerprint.

Cite this