Omalizumab Relieves Aspirin-Exacerbated Respiratory Disease

By Will Boggs MD

April 07, 2020

NEW YORK (Reuters Health) - Omalizumab reduces aspirin hypersensitivity and lowers leukotriene E4 (LTE4) levels in patients with aspirin-exacerbated respiratory disease (AERD), researchers in Japan report.

AERD manifests as asthma, hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs, chronic rhinosinusitis, mast cell activation, and overproduction of cysteinyl leukotrienes. Systemic corticosteroid treatment can attenuate symptoms, but no anti-asthma medications completely suppress aspirin hypersensitivity, which can continue throughout life.

Dr. Masami Taniguchi of the National Hospital Organization Sagamihara National Hospital, in Sagamihara, and Shonan Kamakura General Hospital, in Kamakura, and colleagues previously showed that 12 months of treatment with omalizumab reduced upper and lower respiratory tract symptoms and urinary levels of LTE4 in patients with AERD.

In the current study, they evaluated the efficacy of omalizumab against the overproduction of LTE4 following aspirin challenge, severe upper and lower respiratory symptoms, and aspirin hypersensitivity in a crossover trial of 16 patients (median age, 53 years) with AERD.

Compared with the placebo phase, there was a significant reduction in the overall production of LTE 4 following oral aspirin challenge, the primary endpoint, during the omalizumab phase, the researchers report in the American Journal of Respiratory and Critical Care Medicine.

The urinary levels of LTE4 at each time point after oral aspirin challenge were significantly lower in the omalizumab phase than in the placebo phase.

The median cumulative provocation dose of aspirin in the placebo phase was 150 mg, whereas 10 of 16 patients did not show a positive reaction to aspirin in the omalizumab phase even after the highest cumulative dose of 930 mg was administered.

In four of the six patients who still had a positive response, the cumulative provocation dose increased from 90 mg to 210 mg. The provocation dose was unchanged in the other two patients.

Seven of 16 patients reported a response to treatment within seven days of beginning omalizumab treatment, and 11 of 16 patients had a response at month three. Three patients responded within the first day of the omalizumab treatment. Two of 16 patients responded during the placebo phase.

During the omalizumab phase, patients experienced significant improvements in respiratory symptoms and all respiratory functions except for forced vital capacity (% predicted) and fractional exhaled nitric oxide.

"These findings indicate that omalizumab has efficacy against the key pathogenic features of AERD and might be an important therapeutic candidate for AERD," the authors conclude.

Dr. Hae-Sim Park of Ajou University School of Medicine, in Suwon, South Korea, who recently reviewed the management of AERD, told Reuters Health by email, "This study demonstrates the beneficial effect of this drug on AERD."

"We can expect the beneficial effects of omalizumab via suppressing mast cells and eosinophilic inflammation of upper and lower airway mucosa in AERD patients," said Dr. Park, who was not involved in the study.

Dr. Anne Y. Liu, who directs the aspirin-desensitization program at Stanford University, in Stanford, California, told Reuters Health by email, "In our normal clinical practice: a) omalizumab can facilitate difficult desensitizations, including for food and medications, but usually we reserve it for situations in which normal desensitization procedures don't work; b) aspirin desensitization can be safely done with the vast majority of AERD patients with premedication with montelukast or zileuton, and we rarely run into situations in which a patient cannot be desensitized to the goal dose."

"The clinical need might be to know whether omalizumab could facilitate difficult aspirin desensitizations in which patients keep reacting despite premedication with montelukast or zileuton, both oral medications that are fairly readily available (and montelukast is quite inexpensive)," said Dr. Liu, who also was not part of the new research. "I would imagine it would be helpful, but that is not what was studied here - these were patients with milder AERD who did not get any premedication for desensitization."

"Another clinical need might be to know whether omalizumab could replace aspirin for control of AERD, which is also not what was studied here; while it worked for their asthma (which is the FDA-approved indication), sinus disease was essentially excluded (and the literature suggests it doesn't work well for AERD-related sinus disease)," Dr. Liu said.

The study had no commercial funding. One of the authors reports financial ties to Novartis, which markets omalizumab as Xolair with Genentech.

Dr. Taniguchi did not respond to a request for comments.

SOURCE: American Journal of Respiratory and Critical Care Medicine, online March 6, 2020.