Earlier Reduction of Allergic Response With Omalizumab in Moderate to Severe Allergic Asthma

Results of a small single-center study published in Allergy showed that omalizumab led to reductions in allergic response much earlier than previously observed.¹

The study was led by researchers from the division of allergology, pulmonology, and cystic fibrosis at University Hospital Frankfurt in Germany.

The monoclonal antibody omalizumab received US Food and Drug Administration (FDA) approval in 2003 for the treatment of moderate to severe allergic asthma. Initial research on the drug found a significant reduction of the early allergic response (EAR) after 4 weeks.² However, the dosing and route of administration used at that time were different from current recommendations. Further studies have primarily examined the effects of omalizumab on EAR and late allergic response (LAR) after 8 weeks or longer, and European recommendations suggest a treatment period of at least 12 to 16 weeks.³

More recent research found a decrease in seasonal allergy exacerbations after 4 weeks of omalizumab therapy, indicating that it may be a promising short-term treatment strategy for seasonal allergies.^4,5 “Additionally, the combination of allergen-specific immunotherapy (SIT) for asthma after treatment with omalizumab is a promising novel therapeutic approach,” the study investigators noted.¹ Elucidating the onset of effects “would strengthen these novel approaches, especially considering omalizumab currently remains the only approved anti-IgE [immunoglobulin E] drug.”

Jordis Trischler, MD, and colleagues aimed to identify the time course of EAR and LAR, as well as basophil activation and exhaled nitric oxide (eNO), in 10 adult patients (6 men; 4 women; median age 24.5) taking omalizumab. Inclusion criteria were mild, well-controlled asthma; no recent exacerbation or corticosteroid treatment; serum immunoglobulin E (IgE) between 300 and 700 IU/mL; and non-smoking status.

Bronchial airway provocation was performed at the screening visit and then at weeks 1, 2, 4, and 8. Participants received the initial omalizumab dose within 24 hours of provocation and subsequent doses every 2 weeks for the remaining 8-week study period. In addition, basophil activation was analyzed to measure allergic IgE-sensitization, and eNO was measured to assess airway inflammation.

The results revealed a significant decrease in EAR after 4 weeks (change in forced expiratory volume in 1 second (ΔFEV₁) 28% vs 11%; P <.001), and a reduction in LAR after 1 week (ΔFEV₁ 26% vs 13%, P <.05). Further reductions in LAR were noted after 2 weeks [6.9% (5.3%-33.3%), P <.05] and 4 weeks [1.2% (−9.9% to 8.2%), P <.001], with sustained improvement after 8 weeks [3.6% (−4.7% to 13.8%), P <.001]. Basophil activation (CD63 expression: 79% vs 32%, P <.05) and eNO (86 vs 53 ppb; P <.05) were reduced after 2 weeks.

These findings “might improve the clinical applications of omalizumab by showing the onset of the protective effect in allergic asthma after 4 weeks of treatment,” the investigators concluded.

Study Limitations:

• The current study did not measure exacerbations as a clinical parameter
• Generalizability may be limited as the study examined a small cohort with mild asthma

References

1. Trischler J, Lieb A, Arnold M, et al. Omalizumab effectively protects against early- and late allergic responses in asthma after 4 weeks [published online June 28, 2017]. Allergy. doi:10.1111/all.13217
2.  Boulet LP, Chapman KR, Côté J, et al, Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Am J Respir Crit Care Med. 1997;155(6):1835-1840. doi:10.1164/ajrccm.155.6.9196083
3. Bousquet J, Wenzel S, Holgate S, Lumry W, Freeman P, Fox H. Predicting response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. Chest. 2004;125(4):1378-1386. doi:10.1378/chest.125.4.1378
4. Busse WW, Morgan WJ, Gergen PJ, et al., Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364(11):1005-1015. doi:10.1056/NEJMoa1009705
5. Teach SJ, Gill MA, Togias A, et al. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol. 2015;136(6):1476-1485. doi:10.1016/j.jaci.2015.09.008
6. Kopp, M.V., et al., Combination of omalizumab and specific immunotherapy is superior to immunotherapy in patients with seasonal allergic rhinoconjunctivitis and co-morbid seasonal allergic asthma. Clin Exp Allergy. 2009;39(2):271-279. doi:10.1111/j.1365-2222.2008.03121.x