Introduction
Severe asthma affects 5–10% of all individuals with asthma1–4 and poses a significant therapeutic challenge. A large proportion of these patients exhibit high type-2 inflammation, characterized by eosinophilic inflammation and IgE-mediated atopic responses.5 The introduction of biologics has enhanced the management of severe asthma by targeting these inflammatory pathways.6 However, the high cost of biologics raises concerns regarding healthcare resource allocation and limits access to these treatments. This issue could be resolved by accurately identifying appropriate patients and treating them with omalizumab (OML), the oldest and one of the most widely used anti-IgE biologics for severe asthma.
OML, like other biologics, has well-established efficacy in reducing exacerbations and systemic corticosteroid use in severe asthma patients.7,8 However, unlike other biologics, OML dosing is dependent on body weight and serum IgE levels. This unique characteristic raises the possibility of achieving good asthma control in some patients with relatively lower doses of OML. Additionally, OML has shown efficacy in treating allergic rhinitis (AR), a common comorbidity and a known risk factor for poor asthma control.9,10 Considering these factors, some patients with long-term asthma control on omalizumab (OML) appear to achieve effective management of both asthma and exacerbation-related comorbidities such as allergic rhinitis with relatively low doses of OML. In such cases, the healthcare costs associated with biologic therapy may be substantially reduced. Nonetheless, despite prior studies analyzing patient characteristics associated with the clinical benefits of OML,11–13 few studies have specifically examined the relationships among disease control, dosage, and cost-effectiveness.
Therefore, the aim of this study was to clarify the clinical characteristics of patients with severe asthma who maintain long-term control on omalizumab (OML), focusing on both clinical profiles and healthcare cost considerations. We hypothesize the existence of a subgroup that combines clinical efficacy with a reduced economic burden. We aimed to advance personalized medicine by providing new insights into the optimal use of medical resources, complementing current strategies for biological selection.
Materials and Methods
Study Design and Participants
This was a retrospective, observational, multicenter cohort study. This study included patients who were receiving ongoing biologic therapy for severe asthma at Kyoto University Hospital, Kindai University Hospital, and Kindai University Nara Hospital between 2021 and 2023, and who had a history of omalizumab treatment. Patients were excluded if they were current smokers, had significant respiratory comorbidities, or were deemed unsuitable by their physician. This study was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the institutional review boards of all the participating hospitals (R4011). Informed consent was obtained in accordance with ethical guidelines for retrospective studies.
Measurements
We collected clinical data prior to the initiation of biologic therapy. These data included anthropometric measurements (height, weight, and BMI), blood test results (eosinophil count and serum IgE level), lung function test results, fractional exhaled nitric oxide (FeNO) concentrations, when available, inhaled corticosteroid (ICS) dose (fluticasone equivalent), oral corticosteroid (OCS) use, history of AR or eosinophilic chronic rhinosinusitis (ECRS), and data on exacerbations. At enrollment, we also collected data on exacerbations in the past year, history of biologics treatments, and OML dosage. Asthma exacerbations were defined as events requiring systemic corticosteroid treatment. For each type and dose of biologic used at enrollment, we also calculated monthly personal payments on the basis of the Japanese health insurance system (Supplementary Figure 1). The actual prices of biologics were derived from the syringe formulation drug prices as of December 2023. Currency conversion from yen (JPY) to US dollars (USD) was performed using the market exchange rate on December 31, 2023 (1 USD = 142 JPY).
Decisions to switch biologics are made by pulmonology and allergy specialists based on clinical judgment of poor control in exacerbations requiring systemic corticosteroid or symptoms that significantly impair daily functioning. Patients who continued OML for at least four months at enrollment were classified into the C-OML group. Patients who had previously been treated with OML but were not receiving it at enrollment due to a change to other biologics were classified into the S-OML group (Supplementary Figure 2). Type-2 inflammation severity was categorized on the basis of the blood eosinophil count and FeNO level. Patients with an elevated blood eosinophil count (≥ 300/μL) or increased FeNO levels (≥ 50 ppb) were classified as having severe type-2 inflammation; all others were classified as having nonsevere type-2 inflammation.
Statistical Analysis
The C-OML and S-OML groups were compared using the chi-square test, t test, or Wilcoxon rank-sum test, as appropriate. The same statistical methods were used to compare the characteristics of patients with severe and nonsevere type-2 inflammation. A p value < 0.05 was considered to indicate statistical significance. All analyses were performed using JMP version 12 (SAS Institute Inc., Tokyo, Japan). The data are presented as the means ± SDs or medians (ranges).
Results
Patients’ Characteristics
A total of 47 were eligible for inclusion in this study (Supplementary Figure 2). The mean age was 64 ± 16 years, and 72% of the participants were female. The median blood eosinophil count was 243/μL (range: 148–632), the serum IgE level was 144 IU/mL (49–478), and the FeNO level (measured in 38 patients) was 37 ppb (25–75) before biologics were administered. Twenty-five patients (55%) had C-OML status, whereas 22 (45%) had S-OML status. Patients who discontinued omalizumab were subsequently treated with mepolizumab, benralizumab, or dupilumab (Table 1). Most of the reasons for the changes from OML to other medicines were exacerbations or poor disease control, including patients requiring treatment for eosinophilic pneumonia. In one patient, OML was switched to dupilumab to manage ECRS. Both groups were stably continuing their respective biologics for more than four months at the time of enrollment. The median personal payment of biologic therapy was 123 USD (62–247) per month across all subjects.
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Table 1 Patient Characteristics
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Comparison of the C-OML and S-OML Groups
The median duration of omalizumab use in the C-OML group was 40 months. There were no significant differences between the two groups in baseline ICS dose, pulmonary function, or exacerbation history prior to biologic initiation (Table 2). On the otherhand, compared with the S-OML group, the C-OML group presented a significantly greater prevalence of overweight (BMI ≥ 25) (40% vs 14%, p = 0.04), a lower frequency of comorbid ECRS (8% vs 41%, p < 0.01), lower FeNO levels (median 25 ppb vs 57 ppb, p < 0.01), and trends toward a higher frequency of comorbid AR (76% vs 50%, p = 0.06) and lower blood eosinophil counts (median 220/μL vs 452/μL, p = 0.08) (Table 2). In the multivariate analysis including these factors, only ECRS remained significantly different between the groups. In a subgroup analysis excluding patients with ECRS, elevated FeNO (p = 0.03) and comorbid AR (p = 0.01) were significantly more frequent in the C-OML group. At the time of enrollment, ie, while on biologics, the C-OML group achieved exacerbation control comparable to that of the S-OML group, with a median OML dose of 300 mg/month, and had significantly lower monthly personal payments for biologics than did the S-OML group (median: $62 [57 to 154] vs $225 [123 to 249], p < 0.01; Table 2 and Figure 1).
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Table 2 Clinical Characteristics of the C-OML and S-OML Groups
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Figure 1 Comparison of monthly personal payments for biologics between the C-OML and S-OML groups. Abbreviations: US, United States; C-OML, continued omalizumab; S-OML, switched from omalizumab. Notes: The boxes represent the interquartile range, encompassing the middle 50% of the data. The lines within the box indicate the median value. The whiskers depict the range of the data, extending from the lower to the upper quartiles.
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Type-2 Inflammation and OML Response
The status of type 2 inflammation prior to biologic initiation, assessed by eosinophil count or FeNO, was available for 40 patients. Among these, 26 patients (65%) were classified into the severe type-2 inflammation group (eosinophils ≥ 300/μL or FeNO ≥ 50 ppb), whereas 14 patients (35%) were classified into the nonsevere type-2 inflammation group (Table 3). In the nonsevere type-2 inflammation group, a significantly greater proportion of C-OML cases was observed (Figure 2 and Table 3, 79% vs 31%, p < 0.01). Additionally, monthly biologic costs were significantly lower in this group (median: $62 [41–195] vs $166 [106–249], p = 0.02). The proportion of patients who experienced exacerbations in the year prior to enrollment was similar between the two groups.
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Table 3 Clinical Background of the Nonsevere Vs Severe Type-2 Inflammatory Groups
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Figure 2 Distribution of C-OML and S-OML subjects according to type-2 inflammation status. Abbreviations: FeNO, fractional exhaled nitric oxide; C-OML, continued omalizumab; S-OML, switched from omalizumab. Notes: The distributions of C-OML and S-OML subjects according to type-2 inflammation are shown. Subjects with blood eosinophils ≥ 300/μL or FeNO ≥ 50 ppb at enrollment were classified into the severe type-2 inflammation group, whereas those meeting neither criterion were classified into the nonsevere type-2 inflammation group. Dots represent individual patient data, illustrating the distribution. The red panel indicates severe type-2 inflammatory status, whereas the blue panel indicates nonsevere type-2 inflammatory status.
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Discussion
In this study, we compared patients who responded well to omalizumab with those who required switching to other biologics and identified characteristics of the former group. These patients were more likely to have allergic rhinitis and relatively higher BMI, and they incurred significantly lower out-of-pocket costs for biologic therapy. Our findings suggest that considering these clinical characteristics could help optimize biologic selection and enhance cost-effectiveness in severe asthma management.
While biologics are highly effective in controlling severe asthma and reducing exacerbations,6,14 their high cost remains a significant concern.15 In countries such as Japan, where insurance systems result in personal payments that vary depending on treatment regimens, the financial burden of biologics remains a significant barrier.16 The monthly cost of 300 mg of OML for users in the 30%-payer group of the Japanese insurance system, the largest group in this study, was 17,488 yen (123.2 USD). In comparison, the costs of other drugs were at least double the cost: mepolizumab at 47,967 yen (337.8 USD), benralizumab at 47,901 yen (337.3 USD), and dupilumab at 35,265 yen (248.3 USD). Conversely, the costs of other agents are comparable to those of 600 mg of OML. Among biologics, OML has demonstrated good cost-effectiveness in several studies, as evaluated using quality-adjusted life years (QALYs)17 and the incremental cost-effectiveness ratio (ICER).18 This study extends previous research by identifying a population that can be effectively controlled with relatively low-dose OML (median 300 mg/month), offering a potential solution to this economic issue. Biologics have become indispensable in the management of severe asthma. To ensure access for all eligible patients, it is essential to develop strategies that address not only disease pathophysiology and therapeutic efficacy but also economic considerations.
Our study identified patients with nonsevere type-2 inflammation as a population sensitive to OML. Numerous studies have described the characteristics of responders and nonresponders to biologics in severe asthma,19,20 generally reporting that biologics, including OML, are more effective in patients with high type-2 inflammation.19 However, one study reported that the efficacy of OML is not influenced by blood eosinophil counts.21 Furthermore, a network meta-analysis indicated that OML demonstrated relatively mild effects compared with other biologics in terms of exacerbation suppression, symptom improvement, and lung function improvement in patients with eosinophilic (≥ 300/μL) asthma.22 Our findings align with these reports, suggesting that the efficacy of OML appears to be limited in patients with excessively elevated type-2 inflammation but is effective in patients with nonsevere type-2 inflammation.
Another characteristic of patients in whom OML was effective was increased BMI. Overweight and obesity have been linked to poorer responses to biologics,19 possibly because severe type-2 inflammation is more commonly observed in leaner patients,23,24 and neutrophilic systemic inflammation in obesity may hinder the response to biologics.25,26 Indeed, patients who were overweight tended to be more likely to be in the nonsevere type 2 inflammation group in this study. However, most of the patients with a BMI ≥ 25 were classified as having “relatively increased body weight” rather than being severely obese, suggesting that systemic nontype-2 inflammation was likely mild in this study of Japanese participants. One might assume that the cost of OML in obese patients increases since the dose of OML increases with weight gain. However, 300 mg/month OML can still be administered to patients weighing up to 90 kg if their IgE levels are less than 200 IU/mL. Taken together, this population may be treated with OML in a cost-effective manner.
The high prevalence of comorbid AR in this cohort is also important to consider. A previous study revealed that the coexistence of AR and overweight (BMI ≥ 25) worsens lung function and airway inflammation.27 Continued OML treatment in overweight or obese patients may have contributed to better AR management,26 which in turn likely improved asthma control. AR is associated with exacerbated mood disorders, reduced activity levels,28 and increased sleep disturbances,29 all of which are risk factors for asthma exacerbations. This study suggests that even when factors such as nonsevere type-2 inflammation or overweight seemingly indicate poor responsiveness to biologics, addressing coexisting treatable traits can help maximize the therapeutic potential of biologic treatments.
The ultimate goal in severe asthma management is off-treatment remission.30 However, ongoing biologic therapy is crucial, as discontinuation increases the risk of exacerbations and symptom worsening.31–34 Sustained use of biologics minimizes these risks, enhances remission rates, and stabilizes asthma control.35 While the high cost of biologics often hinders their use, OML’s affordability and strong safety profile36–39 make it a practical option for continued treatment of severe asthma.
This study has several limitations. First, since this was a retrospective analysis, a prospective study is needed to confirm whether the identified phenotype truly benefits from OML treatment. Second, medical cost evaluations may lack accuracy. In Japan, a high-cost medical expense system covers costs exceeding a threshold on the basis of income, but this was not accounted for in the present study. We also focused solely on costs related to the use of biologics, and we excluded expenses related to severe asthma exacerbations. However, even in hypothetical evaluations where the S-OML group used the high-cost medical system, the C-OML group incurred less expenses (data not shown). Moreover, as exacerbation frequencies were similar between the groups, the results are unlikely to be significantly affected. Third, in the present study, we defined effectiveness as the stable continuation of OML, whereas clinical remission has become the treatment goal.30 These may be insufficient as clinical indicators. However, this study emphasizes economic aspects, and we confirmed that there was no significant difference in exacerbation history between the two groups. Fourth, the small sample size may limit the reliability of the results. To address this limitation, we performed an analysis using data from multiple institutions; however, further studies with larger cohorts and external validation are needed to strengthen the generalizability of the findings.
Conclusion
In conclusion, this study clarified the characteristics of patients with severe asthma who achieved long-term stability with omalizumab (OML). These patients exhibited relatively high BMI and mild type 2 inflammation, and were associated with a lower treatment burden related to biologic therapy. Further investigation with a larger sample size and validation are necessary, but these findings suggest the importance of considering both clinical and economic factors when personalizing biologic therapy for severe asthma.
Abbreviations
OML, omalizumab; FeNO, fractional exhaled nitric oxide; ICS, inhaled corticosteroid; OCS, oral corticosteroid; AR, allergic rhinitis; ECRS, eosinophilic chronic rhinosinusitis; C-OML, patients who continued omalizumab; S-OML, patients who switched from omalizumab; USD, United States dollars; JPY, Japanese yen.
Data Sharing Statement
The datasets used in this study can be obtained from the corresponding author upon reasonable request.
Ethics Approval and Informed Consent
The study protocol was approved by the institutional review boards of all the participating hospitals (R4011). Informed consent was obtained in accordance with ethical guidelines for retrospective studies.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; have drafted or written, or substantially revised or critically reviewed the article; have agreed on the journal to which the article will be submitted; reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage; Agree to take responsibility and be accountable for the contents of the article.
Disclosure
HS and SS belong to an endowed course funded by donations from Fukuda Denshi, Fukuda Lifetec Keiji and ResMed. HM has received lecture fees from AstraZeneca, GlaxoSmithKline, Sanofi, Novartis and Kyorin unrelated to this study. KN has received lecture fees from AstraZeneca and Sanofi unrelated to this study. TO has received lecture fees from Glaxo Smith Kline, AstraZeneca, Boehringer Ingelheim, and Kyowa Kirin unrelated to this study. SS has received grants from Nippon Boehringer Ingelheim and FujiFilm outside this study. HT lecture fees from AstraZeneca, Sanofi, and Nippon Boehringer Ingelheim unrelated to this study. The rest have no conflicts of interest to disclose regarding this study.
References
1. Hekking PPW, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015;135(4):896–902. doi:10.1016/j.jaci.2014.08.042
2. Nagase H, Adachi M, Matsunaga K, et al. Prevalence, disease burden, and treatment reality of patients with severe, uncontrolled asthma in Japan. Allergol Int. 2020;69(1):53–60. doi:10.1016/j.alit.2019.06.003
3. Kimura Y, Suzukawa M, Jo T, et al. Epidemiology of patients with severe asthma in Japan: a nationwide descriptive study. ERJ Open Res. 2024:10. doi:10.1183/23120541.00122-2024.
4. Chupp G, Murphy KR, Gandhi HN, Gilbert I, Bleecker ER. Asthma control in the United States: relationships between short-acting β2-agonist and systemic corticosteroid use. Ann Allergy Asthma Immunol. 2024;133:302–309. doi:10.1016/j.anai.2024.05.003
5. Frøssing L, Silberbrandt A, Von Bülow A, Backer V, Porsbjerg C. The prevalence of subtypes of type 2 inflammation in an unselected population of patients with severe asthma. J Allergy Clin Immunol Pract. 2021;9(3):1267–1275. doi:10.1016/j.jaip.2020.09.051
6. Agache I, Akdis CA, Akdis M, et al. EAACI Biologicals Guidelines-Recommendations for severe asthma. Allergy. 2021;76(1):14–44. doi:10.1111/all.14425
7. Humbert M, Beasley R, Ayres J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 2005;60(3):309–316. doi:10.1111/j.1398-9995.2004.00772.x
8. Hanania NA, Wenzel S, Roseń K, et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med. 2013;187(8):804–811. doi:10.1164/rccm.201208-1414OC
9. Oka A, Matsunaga K, Kamei T, et al. Ongoing allergic rhinitis impairs asthma control by enhancing the lower airway inflammation. J Allergy Clin Immunol Pract. 2014;2(2):172–178. doi:10.1016/j.jaip.2013.09.018
10. Casale TB, Condemi J, LaForce C, et al. Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA. 2001;286(23):2956–2967. doi:10.1001/jama.286.23.2956
11. Kallieri M, Papaioannou AI, Papathanasiou E, Ntontsi P, Papiris S, Loukides S. Predictors of response to therapy with omalizumab in patients with severe allergic asthma – a real life study. Postgrad Med. 2017;129(6):598–604. doi:10.1080/00325481.2017.1321945
12. Li B, Huang M, Huang S, et al. Prediction of clinical response to omalizumab in moderate-to-severe asthma patients using the change in total serum IgE level. J Thorac Dis. 2020;12(12):7097–7105. doi:10.21037/jtd-20-2073
13. Djukanović R, Brinkman P, Kolmert J, et al. Biomarker predictors of clinical efficacy of the anti-IgE biologic omalizumab in severe asthma in adults: results of the SoMOSA study. Am J Respir Crit Care Med. 2024;210(3):288–297. doi:10.1164/rccm.202310-1730OC
14. Kyriakopoulos C, Gogali A, Markozannes G, Kostikas K. Biologic agents licensed for severe asthma: a systematic review and meta-analysis of randomised controlled trials. Eur Respir Rev. 2024;33(172). doi:10.1183/16000617.0238-2023
15. Domínguez-Ortega J, Phillips-Anglés E, Barranco P, Quirce S. Cost-effectiveness of asthma therapy: a comprehensive review. J Asthma. 2015;52(6):529–537. doi:10.3109/02770903.2014.999283
16. Tamada T, Sugiura H. Addressing therapeutic inertia for asthma biologics: lessons from the KOFU study. Respir Investig. 2023;61(6):815–823. doi:10.1016/j.resinv.2023.09.001
17. Brown R, Turk F, Dale P, Bousquet J. Cost-effectiveness of omalizumab in patients with severe persistent allergic asthma. Allergy. 2007;62(2):149–153. doi:10.1111/j.1398-9995.2006.01310.x
18. Arrobas A, Barbosa MP, Rabiais S, Vandewalle B, Félix J. Cost-effectiveness of omalizumab in real world uncontrolled allergic asthma patients. Pulmonology. 2021;27(2):124–133. doi:10.1016/j.pulmoe.2020.03.001
19. McDowell P, McDowell R, Busby J, et al. Clinical remission in severe asthma with biologic therapy: an analysis from the UK severe asthma registry. Eur Respir J. 2023;62(6):2300819. doi:10.1183/13993003.00819-2023
20. Oishi K, Hamada K, Murata Y, et al. A real-world study of achievement rate and predictive factors of clinical and deep remission to biologics in patients with severe asthma. J Clin Med. 2023;12(8):2900. doi:10.3390/jcm12082900
21. Humbert M, Taillé C, Mala L, Le Gros V. Omalizumab effectiveness in patients with severe allergic asthma according to blood eosinophil count: the STELLAIR study. Available from: https://erj.ersjournals.com/content/51/5/1702523.short.
22. Pitre T, Jassal T, Angjeli A, et al. A comparison of the effectiveness of biologic therapies for asthma: a systematic review and network meta-analysis. Ann Allergy Asthma Immunol. 2023;130(5):595–606. doi:10.1016/j.anai.2022.12.018
23. Sunadome H, Matsumoto H, Petrova G, et al. IL4Rα and ADAM33 as genetic markers in asthma exacerbations and type-2 inflammatory endotype. Clin Exp Immunol. 2017;47(8):998–1006. doi:10.1111/cea.12927
24. Izuhara K, Nunomura S, Nanri Y, Ono J, Takai M, Kawaguchi A. Periostin: an emerging biomarker for allergic diseases. Allergy. 2019;68:1–13. doi:10.15036/arerugi.68.1
25. Shore SA. Obesity and asthma: possible mechanisms. J Allergy Clin Immunol. 2008;121(5):
26. Scott H, Ng SH, McLoughlin R, et al. Effect of obesity on airway and systemic inflammation in adults with asthma: a systematic review and meta-analysis. Thorax. 2023;78:957–965. doi:10.1136/thorax-2022-219268
27. Ciprandi G, Ricciardolo FLM, Signori A, et al. Increased body mass index and bronchial impairment in allergic rhinitis. Am J Rhinol Allergy. 2013;27(6):e195–201. doi:10.2500/ajra.2013.27.3979
28. Lee GN, Koo HYR, Han K, Lee YB. Analysis of quality of life and mental health in patients with atopic dermatitis, asthma and allergic rhinitis using a nation-wide database, KNHANES VII. Allergy Asthma Immunol Res. 2022;14(2):273–283. doi:10.4168/aair.2022.14.2.273
29. Muñoz-Cano R, Ribó P, Araujo G, Giralt E, Sanchez-Lopez J, Valero A. Severity of allergic rhinitis impacts sleep and anxiety: results from a large Spanish cohort. Clin Transl Allergy. 2018;8:23. doi:10.1186/s13601-018-0212-0
30. Menzies-Gow A, Bafadhel M, Busse WW, et al. An expert consensus framework for asthma remission as a treatment goal. J Allergy Clin Immunol. 2020;145(3):757–765. doi:10.1016/j.jaci.2019.12.006
31. Ledford D, Busse W, Trzaskoma B, et al. A randomized multicenter study evaluating Xolair persistence of response after long-term therapy. J Allergy Clin Immunol. 2017;140(1):162–169.e2. doi:10.1016/j.jaci.2016.08.054
32. Vennera MDC, Sabadell C, Picado C, Spanish Omalizumab Registry. Duration of the efficacy of omalizumab after treatment discontinuation in “real life” severe asthma. Thorax. 2018;73(8):782–784. doi:10.1136/thoraxjnl-2017-210017
33. Hamada K, Oishi K, Murata Y, Hirano T, Matsunaga K. Feasibility of discontinuing biologics in severe asthma: an algorithmic approach. J Asthma Allergy. 2021;14:1463–1471. doi:10.2147/JAA.S340684
34. Kimura H, Konno S, Makita H, et al. Prospective predictors of exacerbation status in severe asthma over a 3-year follow-up. Clin Exp Allergy. 2018;48(9):1137–1146. doi:10.1111/cea.13170
35. Chipps BE, Lugogo N, Carr W, et al. On-treatment clinical remission of severe asthma with real-world longer-term biologic use. J Allergy Clin Immunol Glob. 2025;4(1):100365. doi:10.1016/j.jacig.2024.100365
36. Ohta K, Miyamoto T, Amagasaki T, Yamamoto M, 1304 Study Group. Efficacy and safety of omalizumab in an Asian population with moderate-to-severe persistent asthma. Respirology. 2009;14(8):1156–1165. doi:10.1111/j.1440-1843.2009.01633.x
37. Mansur AH, Srivastava S, Mitchell V, Sullivan J, Kasujee I. Longterm clinical outcomes of omalizumab therapy in severe allergic asthma: study of efficacy and safety. Respir Med. 2017;124:36–43. doi:10.1016/j.rmed.2017.01.008
38. Di Bona D, Fiorino I, Taurino M, et al. Long-term “real-life” safety of omalizumab in patients with severe uncontrolled asthma: a nine-year study. Respir Med. 2017;130:55–60. doi:10.1016/j.rmed.2017.07.013
39. Adachi M, Kozawa M, Yoshisue H, et al. Real-world safety and efficacy of omalizumab in patients with severe allergic asthma: a long-term post-marketing study in Japan. Respir Med. 2018;141:56–63. doi:10.1016/j.rmed.2018.06.021