Omalizumab eases extra-respiratory symptoms in aspirin-exacerbated respiratory disease

Key takeaways:

• The percentage of patients experiencing chest pain exacerbations fell from 6% to 0%.
• Daily inhaled corticosteroid doses fell from 800 to 400 µg.
• Omalizumab attenuated symptoms during aspirin challenges.

The extra-respiratory symptoms of aspirin-exacerbated respiratory disease improved with omalizumab at baseline and during aspirin challenges, according to a study published in The Journal of Allergy & Clinical Immunology.

This treatment may enable patients to reduce or eliminate their use of corticosteroids in treating these symptoms, Hiroaki Hayashi, MD, PhD, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, and colleagues wrote in the study.

During the retrospective, observational study, 27 patients (mean age, 60 years; 85.2% female) with aspirin-exacerbated respiratory disease (AERD) received omalizumab (Xolair; Genentech, Novartis) at Sagamihara National Hospital between July 2009 and March 2019.

Also, 21 (77.8%) of these patients were receiving systemic corticosteroid therapy at the start of the omalizumab treatment, which had a median monthly dose of 300 mg (interquartile range [IQR], 150 mg-600 mg).

During the year before omalizumab treatment, 16 (59.3%) patients experienced episodic AERD-related extra-respiratory chest symptoms including angina-like chest pain; gastrointestinal (GI) symptoms including abdominal pain, nausea or diarrhea; or cutaneous symptoms including pruritic, macular eruption, flushing or rash.

Six (22.2%) patients had one or more exacerbations in their chest symptoms, nine (33.3%) patients had one or more GI symptom exacerbations, and 16 (59.3%) patients had one or more cutaneous symptom exacerbations.

After a year of omalizumab treatment, the percentages of patients experiencing one or more exacerbations fell to 0% (P < .001) in the chest group, 7.4% (P = .016) in the GI group and 7.4% (P < .001) in the cutaneous group. The numbers of exacerbations in the chest (P = .035), GI (P = .009) and cutaneous (P < .001) groups fell as well.

The researchers further noted significant reductions in urinary leukotriene E4 (LTE4) concentration (P < .001) and in numbers of asthma exacerbations (P < .001) and hospitalizations (P = .013), daily systemic (P < .001) and inhaled (P = .006) corticosteroid doses and all nasal and asthma-related symptom scores (P < .001 for all).

When the researchers applied Global Evaluation of Treatment Effectiveness guidelines, they found that 24 (88.9%) of the patients — including all 16 who experienced extra-respiratory symptoms — responded to omalizumab.

Also, three patients who had no extra-respiratory symptoms were nonresponders to omalizumab and discontinued treatment. Their respiratory symptoms were less severe than those experienced by the patients who responded to omalizumab, and none of them switched to another biologic after discontinuing their omalizumab treatment.

The 16 patients who experienced extra-respiratory symptoms additionally had higher doses of inhaled corticosteroids (median of fluticasone equivalents per day, 800 µg; IQR, 485 µg-1,000 µg) than those who did not experience extra-respiratory symptoms (median per day, 400 µg; IQR, 320 µg-640 µg; P = .022) at omalizumab initiation.

The extra-respiratory symptom group had higher visual analog scale scores of anosmia (median: 9.6; IQR, 8.7-10 vs. 5; IQR, 3.1-8.4; P = .011) and higher levels of urinary LTE₄ (median level of creatine: 1,074 pg/mg; IQR, 606.9-2,260.3 vs. 427.3 pg/mg; IQR, 197.1-1,386.1) at the beginning or omalizumab treatment as well.

These findings suggest that patients with AERD and extra-respiratory symptoms had more severe disease, the researchers said.

In a follow-up study, the researchers examined three of the 16 patients with extra-respiratory symptoms who also experienced extra-respiratory symptoms during aspirin challenges. All three of these patients experienced cutaneous symptoms during the placebo phase of the challenges.

One of the patients experienced angina-like chest pain. During administration of omalizumab, the amount of aspirin required to induce extra-respiratory symptoms increased from 90 mg to 210 mg.

The second patient experienced abdominal pain but did not experience any symptoms during the omalizumab phase, even after administration of 930 mg of omalizumab, which was the highest cumulative dose.

Finally, the third patient did not experience any extra-respiratory symptoms after 210 mg of omalizumab. 

Based on these findings, the researchers said that treatment with omalizumab suppressed extra-respiratory symptoms during the systemic aspirin challenge.

Overall, the researchers said that omalizumab may stabilize AERD by suppressing systemic mast cell activation. Considering the challenges of aspirin desensitization and desires to reduce corticosteroid usage, the researchers continued, omalizumab may be an effective alternative therapy, although further randomized studies are needed to confirm its efficacy.