Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 14:17:1173-1186.
doi: 10.2147/JAA.S423256. eCollection 2024.

Japanese Patients with Severe Asthma Identified as Responders to Omalizumab Treatment at 2 Years Based on the GETE Score Continued Treatment for an Extended Period

Ai Goto  1 , Sonoko Harada  1   2 , Hitoshi Sasano  1 , Yuuki Sandhu  1 , Yuki Tanabe  1 , Sumiko Abe  1 , Shoko Ueda  1 , Tomohito Takeshige  1 , Kei Matsuno  1 , Tetsutaro Nagaoka  1 , Jun Ito  1 , Ryo Atsuta  1 , Kazuhisa Takahashi  1   3 , Norihiro Harada  1   2   3
Affiliations

Japanese Patients with Severe Asthma Identified as Responders to Omalizumab Treatment at 2 Years Based on the GETE Score Continued Treatment for an Extended Period

Ai Goto et al. J Asthma Allergy. .

Abstract

Purpose: Omalizumab, the anti-IgE monoclonal antibody used to treat severe asthma, reduces asthma exacerbations, hospitalizations, and corticosteroid use. Although allergic asthma is a therapeutic target of omalizumab, omalizumab is not effective in all patients with severe allergic asthma and is not always available for long-term use. We retrospectively investigated factors related to long-term (≥2 years) use of omalizumab for severe asthma.

Patients and methods: Of the 116 patients treated with omalizumab for severe asthma at our hospital between 2009 and 2017, 82 were included in this retrospective analysis. Thirty-four were excluded because of adverse events, financial difficulties, or hospital transfers. The number of asthma exacerbations, unscheduled visits, corticosteroid doses, asthma control test scores, pulmonary function test results, and fractional exhaled nitric oxide levels were evaluated.

Results: The median age of the study population was 58 years, with 66% female and 26% taking regular oral corticosteroids. After 2 years of treatment, 52 responders were identified using the global evaluation of treatment effectiveness (GETE) score. Improvements in asthma control test scores, airflow limitation, exacerbations, and oral corticosteroid use were observed in the responders. Multivariate analysis revealed that a peripheral blood eosinophil count of ≥200 or a perennial antigen-specific IgE antibody positivity of ≥2 predicted a response at the 2-year mark. However, Kaplan-Meier analysis demonstrated that neither high eosinophil counts nor perennial antigen-specific IgE positivity influenced the prolongation of treatment beyond 2 years, and responders at 2 years underwent omalizumab treatment for a significantly longer period than non-responders (HR = 9.89, p < 0.001), with GETE at 2 years being the only predictor of long-term omalizumab use.

Conclusion: In this retrospective study the GETE after 2 years of omalizumab therapy emerged as the most meaningful predictor of the long-term effectiveness of omalizumab treatment in patients with severe asthma, highlighting the benefits of prolonged therapy in certain populations. These findings may guide future therapeutic strategies for severe asthma.

Keywords: GETE; antigen-specific IgE antibody; predictive biomarker.

PubMed Disclaimer

Conflict of interest statement

NH reports personal fees from AstraZeneca, GlaxoSmithKline, Kyorin, Novartis, and Sanofi and grants from AstraZeneca, Daikin, Kao Corporation, Sanofi, and TOSOH outside the submitted work. KT reports grants from Asahi Kasei Pharma Corporation, Bayer Yakuhin, Chugai, Daiichi Sankyo, Eli Lilly, Kyorin, Kyowa Kirin, Nippon Boehringer Ingelheim, Nippon Kayaku, Nippon Shinyaku, Nipro, Novartis, Ono, Pfizer, Sanofi, Shionogi, Taiho, Takeda, Teijin, and Tsumura; and personal fees from Abbott Japan, AstraZeneca, Bristol-Myers, Chugai, Eli Lilly, Janssen, Kyorin, Meiji Seika, Merck, MSD, Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis, Ono, Pfizer, Sumitomo Dainippon Pharma, Taiho, Takeda, Thermo Fisher Scientific, and Viatris outside the submitted work. Furthermore, KT has a patent (P6840330) on the method of detecting cells, managed by Juntendo University in Japan. He is also part of the Board of Directors of The Japan Lung Cancer Society and The Japanese Respiratory Society. All other authors declare that they have no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Use of OCS over time in responders and ROC curve to predict responders to omalizumab treatment. (A) The median reduction in the dose of OCS in the responders, determined by the GETE score after 2 years of omalizumab treatment. The bars indicate the median values. *p < 0.05. (B and C) The cut-off values for the number of eosinophils of 196 (sensitivity, 59%; specificity, 73%; AUC, 0.622; p = 0.07) (B) and positive perennial antigen-specific IgE antibodies of 1.5 (sensitivity, 87%; specificity, 70%; AUC, 0.822; p < 0.001) (C) to differentiate between responders and non-responders are indicated with arrows.
Figure 2
Figure 2
Kaplan–Meier estimates of cumulative rates of time to discontinuation of omalizumab treatment. The patients were divided into two groups: those with peripheral blood eosinophils of ≥200 and those with <200 before omalizumab treatment (A–C); or those with ≥2 positive IgE for perennial specific antigens and those with ≤1 (D–F). Kaplan–Meier analysis for the period leading up to 2 years (A and D), beyond the 2-year mark (B and E), and beyond the 2-year mark excluding patients who transferred and discontinued hospital visits (C and F), respectively.
Figure 3
Figure 3
Kaplan–Meier estimates of cumulative rates of time to discontinuation of omalizumab treatment. The patients were divided into responders and non-responders based on their GETE scores at 1 (A–C) and 2 years (D–F). Kaplan–Meier analysis for the period leading up to 2 years (A and D), beyond the 2-year mark (B and E), and beyond the 2-year mark excluding patients who transferred and discontinued hospital visits (C and F), respectively.
See this image and copyright information in PMC

References

    1. Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet. 2018;391(10122):783–800. doi:10.1016/S0140-6736(17)33311-1 - DOI - PubMed
    1. Papi A, Ryan D, Soriano JB, et al. Relationship of inhaled corticosteroid adherence to asthma exacerbations in patients with moderate-to-severe asthma. J Allergy Clin Immunol Pract. 2018;6(6):1989–98e3. doi:10.1016/j.jaip.2018.03.008 - DOI - PubMed
    1. Borish L, Culp JA. Asthma: a syndrome composed of heterogeneous diseases. Ann Allergy Asthma Immunol. 2008;101(1):1–8. doi:10.1016/S1081-1206(10)60826-5 - DOI - PubMed
    1. Humbert M, Busse W, Hanania NA, et al. Omalizumab in asthma: an update on recent developments. J Allergy Clin Immunol Pract. 2014;2(5):525–36e1. doi:10.1016/j.jaip.2014.03.010 - DOI - PubMed
    1. McGregor MC, Krings JG, Nair P, Castro M. Role of biologics in asthma. Am J Respir Crit Care Med. 2019;199(4):433–445. doi:10.1164/rccm.201810-1944CI - DOI - PMC - PubMed