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Omalizumab Inhibits Aspirin-Provoked Respiratory Reaction in Patients with Aspirin Exacerbated Respiratory Disease
Saturday, March 5, 2016: 2:15 PM
Room 515A (Convention Center)
David M Lang, MD, , , , ,
Rationale: Omalizumab has anti-inflammatory properties beyond having an impact on IgE (AJRCCM 2004;170:583-93).  We performed a double-blind randomized trial to evaluate the hypothesis that omalizumab can attenuate aspirin-provoked respiratory reaction in patients with aspirin exacerbated respiratory disease (AERD).

Methods: Subjects with AERD who fulfilled FDA-label criteria for omalizumab were randomized 2:1 to receive omalizumab:placebo based on body weight and IgE level for 16 weeks, prior to undergoing aspirin desensitization (AD).  The primary outcome was respiratory reaction (decline in FEV1) during AD; urinary LTE4 levels were also assessed.

Results: Of 72 potential subjects, 56 were excluded mainly based on non-fulfillment of criteria for AERD or FDA-label.  Of 16 enrolled, 11 completed participation.  For placebo:omalizumab groups, mean age (42.7 vs. 45.7 years) and IgE level (65 vs. 121 IU/ml) did not differ significantly (p=NS).  All 4 randomized to placebo had respiratory reactions, including 2 with bronchospasm (FEV1 decline ≥ 20%); 2 of 7 randomized to omalizumab had isolated upper airway reactions, 5 had no respiratory reaction (p = 0.036, Fisher Exact Test).  Assuming a “false-negative” rate of 16% (JACI 1983;71:574-9), the probability these 5 subjects were non-AERD patients and were all randomized to omalizumab is 0.0017 (Exact Binomial Test).  No remarkable differences were observed in urinary LTE4 levels (p=NS).

Conclusions: This is the first randomized trial describing a pharmacologic agent that can completely inhibit aspirin-provoked respiratory reaction in AERD patients.  The mechanism for this protective effect is unclear. Further investigation exploring the therapeutic utility of omalizumab in AERD patients undergoing AD is indicated based on these data.