Clinical and Cost-Effectiveness of Omalizumab in Concomitant Asthma and Chronic Rhinosinusitis with Nasal Polyps: A Real-World Exploratory Study

Abstract

Purpose

Severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) frequently coexist, representing the severe “United Airway Disease” (UAD) phenotype. Although omalizumab is approved for both conditions individually, real-world evaluations of its clinical and economic viability for this concomitant phenotype remain limited. We evaluated the cost-effectiveness of omalizumab add-on therapy in Chinese adults with UAD.

Methods

This 52-week exploratory study compared omalizumab add-on therapy (n=23) with standard care (n=17) in patients with concomitant asthma and CRSwNP. Clinical outcomes included acute exacerbations (AEs), endoscopic sinus surgery (ESS) requirements, asthma control test (ACT) scores, sinus CT Lund-Mackay (LM) scores, corticosteroid and antibiotic exposure. Cost-effectiveness was analyzed from a healthcare provider perspective using 2024 constant prices, with decision uncertainty assessed via 1000-iteration bootstrapping. Scenario analyses evaluated the economic impact of recently approved domestic biosimilars.

Results

At week 52, compared with standard care, the omalizumab add-on group achieved significant reductions in annual AEs (median 0 [IQR 1.00] vs 1.0 [IQR 2.00]; P = 0.037) and ESS rates (8.70% vs 41.18%; P = 0.016). Although cross-sectional ACT scores at week 52 were comparable, omalizumab demonstrated superior peak efficacy with higher best ACT scores (median 25.0 [IQR 1.00] vs 24.0 [IQR 3.00]; P = 0.029) and greater maximum improvement from baseline (mean 7.52 [SD 4.90] vs 4.47 [SD 2.83]; P = 0.018). Omalizumab also produced significantly lower LM scores (median 12.92 [IQR 2.50] vs 18.00 [IQR 0]; P < 0.001) and a profound antibiotic-sparing effect (median duration 0.0 [IQR 8.5] vs 23.0 [IQR 24.0] days; P < 0.001). Total direct medical costs were approximately 7-fold higher (¥44,681.09 [IQR 47,780.91] vs ¥6282.25 [IQR 16,179.90]; P < 0.0001), primarily driven by biologic acquisition costs. Baseline incremental cost-effectiveness ratios (ICERs) for the reference originator were ¥64,223.84 per AE avoided and ¥114,398.72 per ESS avoided, with 0% probability of cost-effectiveness at strict willingness-to-pay thresholds. Substituting the originator with the lowest-priced domestic biosimilar substantially reduced the ICERs to ¥42,943.60 and ¥76,493.28, respectively.

Conclusion

Omalizumab provides superior multi-domain clinical control and profound antibiotic-sparing effects. While the reference originator is not cost-effective over a 52-week horizon at its baseline price in China, stepwise price reductions through centralized procurement and the emergence of affordable biosimilars provides a highly viable economic pathway. Future optimization requires dynamic value-based pricing and targeting high-burden UAD phenotypes.

Plain Language Summary

Patients with asthma often experience chronic rhinosinusitis with nasal polyps (CRSwNP). This combined condition, called “United Airway Disease”, is difficult to treat. Omalizumab is a biologic medication approved to treat both conditions, but we wanted to see if it provides effective and economically valuable treatment in China.

We observed 40 adults with asthma and CRSwNP over one year. Twenty-three received omalizumab plus standard care, while 17 received only standard care. We tracked their asthma flare-ups, sinus surgeries, breathing symptoms, medication use and medical costs.

Omalizumab was highly effective. Patients taking it had significantly fewer asthma flare-ups, needed fewer sinus surgeries and antibiotics. Even though symptoms can fluctuate, people taking omalizumab reached a much higher level of peak symptom relief during the year. However, because the brand-name medication is very expensive, the total treatment costs were significantly higher, meaning it does not currently save money for the healthcare system. This higher cost was primarily driven by the high price of the omalizumab themselves. Fortunately, when we calculated the costs using the prices of newer, more affordable versions of the medication (called biosimilars) recently approved in China, the treatment became a much better financial value.

Overall, omalizumab is an excellent treatment for people with both asthma and CRSwNP. While the original drug is not currently cost-saving over a one-year period, recent price drops and the lower-cost biosimilars greatly improve its financial value. Moving forward, focusing these treatments on the most severely ill patients will ensure the best value for healthcare systems.

Introduction

Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) frequently coexist and are increasingly recognized as manifestations of united airway disease (UAD), in which inflammatory processes involve both the upper and lower airways.^1–3 Up to 65% of individuals have asthma and CRSwNP as comorbid conditions, ranging from 10–30% in patients with mild asthma and 70–90% in patients with moderate to severe asthma.^4–8 Moreover, approximately 20–60% of individuals with type 2 CRSwNP present with coexisting asthma.^9,10 This comorbidity significantly worsens disease outcomes.¹¹ Large-scale real-world registries, including the International Severe Asthma Registry (ISAR), the Global Allergy and Asthma European Network (GALEN) cohort and the Italian Severe Asthma Network (SANI), have systematically captured and monitored this comorbid phenotype, demonstrating that CRSwNP frequently co-occur with severe asthma, are associated with distinct T2-inflammatory biomarker patterns, and independently increase exacerbation frequency and long-term oral corticosteroid use, while longitudinal surveillance further reveals dynamic shifts in these clinical and biological markers over time.^12–14 Consistent with these observations, our recent multimorbidity analysis of 849 asthma patients identified a predominantly respiratory cluster—encompassing CRSwNP—as independently predictive of ICU admission, mechanical ventilation, and recurrent emergency department visits, framing such comorbidities as treatable traits that warrant targeted intervention.¹⁵ Compared with patients with asthma alone, those with both asthma and CRSwNP experience more severe airflow limitations (86.0% vs 48.9%, P <0.001),¹⁶ a 2.3 times greater exacerbation risk,¹⁷ and a greater likelihood of developing corticosteroid dependence (4% vs 1%, P < 0.05).⁷ Furthermore, these patients face a higher recurrence rate of nasal polyps (73.9% vs 29.2%; P < 0.01), and more than 20% of them require four or more surgical interventions, significantly impairing quality of life and increasing the healthcare burden.^18,19

Currently employed treatment strategies for asthma and CRSwNP are largely focused on managing each condition separately: inhaled corticosteroids (ICS) for asthma and nasal corticosteroids for CRSwNP, with oral corticosteroids (OCS) and endoscopic sinus surgery (ESS) reserved for severe cases.^20–24 However, these therapies often fail to fully control symptoms, especially in patients with both conditions.^5,25 Additionally, repeated use of OCS can lead to significant side effects, and patients often require recurrent surgeries or other interventions, contributing to a substantial burden on both the healthcare system and the individual.²⁶ These limitations highlight the inadequacy of traditional symptom-centered strategies, which lack interventions targeting shared inflammatory pathways across the upper and lower airways.²⁷

Building on the “One Airway, One Disease” paradigm, biologic therapies targeting type 2 inflammation represent emerging treatment options for UAD.^28,29 Omalizumab, an anti-IgE monoclonal antibody, has been proven effective at reducing asthma exacerbations and improving control in patients with allergic asthma.³⁰ Moreover, omalizumab has demonstrated efficacy in patients with CRSwNP, significantly improving nasal symptoms and reducing polyp burden.^31,32 It was approved for asthma treatment in 2003, and more recently, it received approval for use in CRSwNP in 2020.³³ Despite the promising dual benefit on asthma symptoms and sinonasal disease, real-world evidence on the effectiveness and burden of omalizumab in UAD is limited. Most studies have focused on asthma or CRSwNP separately, and excluded the heterogeneous treatment responses, variable adherence patterns, and concurrent medication use observed in routine clinical practice.^31,34–36 Real-world evidence is therefore essential for UAD, where cross-airway inflammatory interactions introduce temporal variability that protocol-driven trials cannot replicate.

Furthermore, omalizumab treatment markedly increases direct medical costs, drawing attention to the economic implications of biologic therapy.³⁷ In China, while biologics have become more accessible because of price negotiations (67% price reduction), the affordability of such therapies remains a significant concern for patients and payers alike.³⁸ Concurrently, omalizumab biosimilars have been successfully launched, promising further price competition and broader accessibility.³⁹ However, the cost-effectiveness data for omalizumab, particularly in Asian UAD populations, remain scarce.⁴⁰ Healthcare systems in China face different challenges, including higher out-of-pocket costs and variations in insurance coverage, which make it crucial to generate localized evidence on the cost-effectiveness of biologic treatments such as omalizumab to inform reimbursement decisions.

Therefore, we conducted a single-center, retrospective exploratory cohort study comparing omalizumab add-on therapy with standard therapy in patients with asthma and comorbid CRSwNP over 52 weeks. This study aims to provide real-world evidence on the clinical effectiveness and cost-effectiveness of omalizumab to guide clinical decision-making and inform reimbursement strategies for biologic therapies in the treatment of UAD.

Methods

Study Design

This was a single-center, exploratory, retrospective, real-world cohort study embedded within an established asthma patient registry at the Peking University Third Hospital. Patients with concomitant severe asthma and CRSwNP who received treatment and completed at least 52 weeks of follow-up between January 1, 2019, and December 31, 2024, were evaluated. This study was designed to compare the clinical effectiveness and cost-effectiveness of omalizumab add-on therapy versus standard therapy alone in adults with concomitant asthma and CRSwNP in routine clinical practice. Baseline clinical traits and 52-week longitudinal clinical and cost data were retrospectively extracted from the electronic medical records. The study reporting follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

This study was approved by the Ethics Committee of the Peking University Third Hospital (Approval No. 2024–102-01), and the research was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants before enrollment.

Participants

Patients aged ≥18 years with a diagnosis of asthma, confirmed according to the Global Strategy for Asthma Management and Prevention, and CRSwNP, defined on the basis of the diagnostic criteria established in the Chinese Guidelines for Diagnosis and Treatment of Chronic Rhinosinusitis, were eligible for inclusion.^3,20 All the participants had received standardized therapy at our institution for at least 12 months before enrollment. The exclusion criteria included the use of other biologic therapies (eg, mepolizumab or dupilumab) in the 6 months prior to enrollment, a history of severe allergic reactions to monoclonal antibodies, active tuberculosis or other severe infections, and pregnancy. Patients with significant comorbidities that could interfere with study outcomes, such as malignancies or uncontrolled cardiovascular diseases, were also excluded. Patients without complete baseline or 52-week follow-up data were excluded from the final analyses. Instead of formal propensity matching, which was precluded by the exploratory cohort size, patients in the two treatment groups were carefully evaluated by clinical investigators to ensure baseline comparability in disease severity and treatment intensity. The detailed patient screening and enrollment process is illustrated in the STROBE flow diagram (Figure 1).

Figure 1.

Study flow diagram of patient enrollment and treatment allocation.

Abbreviation: CRSwNP, chronic rhinosinusitis with nasal polyps.

Treatment Groups

Eligible participants were assigned to either the omalizumab add-on cohort or the standard therapy cohort without randomization. The decision to initiate omalizumab was driven by real-world clinical indications, shared decision-making, and the patients’ willingness and ability to pay for biologic therapy. The omalizumab add-on group received omalizumab (Xolair^®, administered subcutaneously every 2 to 4 weeks at doses of 150–600 mg based on body weight and baseline serum IgE levels) as an add-on therapy. The standard care group received only conventional guideline-directed treatments, including ICSs combined with β₂-agonists, nasal corticosteroids, and other supportive measures, such as anticholinergics, theophylline, low-dose oral corticosteroids, antihistamines, and antileukotrienes, and ESS, without the addition of biologics.

Outcomes

The primary clinical outcome was the annual frequency of acute exacerbations over 52 weeks. Acute exacerbations were defined as follows: (i) events requiring systemic corticosteroids (oral or intravenous) for at least 3 days, or (ii) acute care visits/inpatient care due to worsening asthma.⁴¹ Cardinal sinonasal symptoms include nasal congestion/obstruction, facial pain/pressure, anterior/posterior rhinorrhea, and hyposmia/anosmia.²⁶ Exacerbations starting <7 days after a previous episode were considered a single exacerbation.

Secondary clinical outcomes included the following:

Asthma control was assessed by the Asthma Control Test (ACT, score range 5–25). Beyond cross-sectional scores at week 52, we evaluated the best ACT score achieved during the follow-up and the maximum clinical improvement (defined as the net delta change from baseline to the best achieved ACT score) to capture peak therapeutic efficacy. Well-controlled asthma defined as an ACT ≥20.⁴² Paranasal sinus computed tomography Lund–Mackay scores were recorded at baseline and 52 weeks.⁴³ The proportion of patients requiring systemic corticosteroids (SCS) therapy and the incidence of ESS required during the follow-up period.

Exploratory clinical outcomes included the following:

ICS dose step-down and classification (no use and low dose, medium dose, or high dose) at week 52, based on daily budesonide equivalent doses (low 200–400 μg; medium >400–800 μg; and high >800 μg).⁴⁴

Intranasal corticosteroids (NCS) prescription rate was recorded at baseline and 52 weeks.

Antibiotic prescription rate and total duration (days) of systemic antibiotic use for respiratory indications during follow-up.

Cost-Effectiveness Analysis (CEA) and Sensitivity Analysis

The CEA was performed according to both the Chinese Guidelines for Pharmacoeconomic Evaluations (2025) and the Good Practices for Real-World Data Studies of Treatment and/or Comparative Effectiveness developed by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR).^45,46

Direct medical costs, including the costs of hospitalization, outpatient visits, medications, and surgeries, were collected from hospital records over the 52-week follow-up period. Indirect costs (eg, transportation, absenteeism and productivity loss) were not captured and, therefore, were excluded from the base-case analysis. Cost-effectiveness was assessed by calculating incremental cost-effectiveness ratios (ICERs) for prespecified endpoints. The ICER was defined as the difference in the mean total direct medical costs between the omalizumab and standard therapy groups (Δ Cost) divided by the corresponding difference in effectiveness (Δ Effectiveness):

The effectiveness metrics in the CEA included the exacerbation frequency and events of ESS during the follow-up period.

All costs are expressed in Chinese yuan (CNY, ¥). To eliminate the impact of significant price fluctuations for omalizumab between 2019 and 2024 (eg, from ¥3600 to ¥1204 per injection), all medical expenditures were standardized to 2024 constant prices. Discounting was not applied as the individual follow-up period did not exceed one year. ICERs were then re-estimated to reflect current reimbursement conditions.

Uncertainty in the joint distribution of incremental costs and effects was addressed by using nonparametric bootstrap resampling with 1000 iterations. The results are displayed on cost-effectiveness planes, and cost-effectiveness acceptability curves (CEACs) were constructed to show the probability that omalizumab is cost effective across a range of willingness-to-pay (WTP) thresholds per unit of effectiveness gained. To provide a pragmatic and clinically grounded economic interpretation, we adopted event-based treatment costs as the primary benchmarks for WTP. Specifically, the thresholds were set at the average direct medical cost of managing a single acute exacerbation (AE) episode (¥1745.73) and the average cost of an ESS (¥19,431.92). For CEACs interpretation, at a given WTP threshold, the probability of cost-effectiveness was calculated as the proportion of bootstrap replications in which the incremental net benefit was positive. For instance, if the WTP is set at the actual treatment cost of an AE (¥1745.73), and 0% of bootstrap iterations satisfy the cost-effectiveness criterion, it indicates that omalizumab is unlikely to be cost-saving on the basis solely of the immediate direct medical cost-offset of that single event.

Scenario Analysis

To address the rapidly evolving pharmaceutical pricing landscape and the paradigm shift introduced by domestic anti-IgE biosimilars in China, a deterministic scenario analysis was incorporated into the economic analysis. Because marketed biosimilars of omalizumab demonstrate clinical equivalence to the brand-name reference, the incremental clinical effectiveness (Δ Effectiveness) was held constant (−0.57 for AE; −0.32 for ESS).^47,48 Four dynamic pricing scenarios for the omalizumab 150 mg formulation were tested: Scenario 0 utilized the initial study-period price of the brand-name drug (¥1204.00); Scenario 1 applied the 2026-updated National Reimbursement Drug List (NRDL) price (¥986.00); Scenario 2 evaluated the domestic biosimilar omalizumab alpha (Aomaishu^®, ¥900.00); and Scenario 3 utilized the lowest-priced domestic biosimilar omalizumab (Enyetan^®, ¥788.00). The total direct medical costs and corresponding ICERs were systematically re-estimated to determine the shift in economic viability. In March 2025, the US. Food and Drug Administration granted approval to Omlyclo^® (omalizumab-igec, Celltrion) as the first—and currently only—interchangeable omalizumab biosimilar, with full indication parity to the originator, including CRSwNP. However, it has not been submitted for regulatory review in China, and no timeline for Chinese market entry has been announced. Consequently, omalizumab-igec is not included in our scenario analysis.

Statistical Analyses

All the statistical analyses were conducted by using SPSS 27.0 (IBM Corp., Armonk, NY, USA), Microsoft Excel 2021(Microsoft Corp., Redmond, WA, USA), and GraphPad Prism 10.0 (GraphPad Software, San Diego, CA, USA).

Continuous variables were first assessed for normality by using the Shapiro–Wilk test. Normally distributed continuous variables are presented as the mean (standard deviation [SD]), and between-group comparisons were conducted by using the independent Student’s t test; within-group changes from baseline were assessed by using paired t tests. Nonnormally distributed continuous variables are reported as medians (interquartile ranges [IQRs]) and were compared between groups with the Mann–Whitney U-test and within groups with the Wilcoxon signed-rank test. Categorical variables are summarized as counts and percentages (%) and were analyzed using the chi-square or Fisher’s exact test. Although multiple imputation was pre-specified for handling missing data, complete longitudinal datasets were successfully obtained for all 40 enrolled patients. Consequently, all analyses were performed entirely on the observed complete-case dataset. A two-tailed P value < 0.05 was defined as the threshold for statistical significance.

For the economic evaluation, 95% confidence intervals (CIs) for incremental costs, effects, and ICERs were derived from the bootstrap replications. No formal adjustment for multiple comparisons was applied, and findings from secondary and exploratory analyses were interpreted with appropriate caution.

Results

Study Population and Baseline Characteristics

A total of 40 patients with asthma and comorbid CRSwNP were included in the final analysis (omalizumab add-on group, n=23; standard therapy group, n=17). Baseline demographic and clinical characteristics were well-balanced between the two cohorts (all P > 0.05). Specifically, there were no significant between-group differences in terms of age, sex, BMI, type 2 inflammatory biomarkers, baseline acute exacerbation frequency, pulmonary function parameters, ACT scores, Lund-Mackay scores, prior ESS frequency, and maintenance topical corticosteroids use (Table 1).

Table 1.

Baseline Characteristics of Patients with Asthma and Comorbid CRSwNP

	Omalizumab Add-On Group, N=23	Standard Care Group, N=17	P value
Age, years
Mean (SD)	46.17 (13.67)	46.11 (11.05)	0.989
Gender, no. (%)
Female	13.00 (56.52)	6.00 (35.29)	0.157
BMI, kg/m2
Mean (SD)	24.26 (3.45)	23.85 (2.64)	0.685
Serum total IgE, IU/mL
Median (IQR)	312.00 (427.25)	287.00 (310.00)	0.420
Blood eosinophils count, cells/μL
Mean (SD)	491.74 (246.42)	449.41 (227.52)	0.582
Tobacco use, no. (%)
Never	20 (86.96)	14 (82.35)	0.499
Current smoker	0 (0)	1 (5.88)
Former smoker	3 (13.04)	2 (11.76)
Total no. of AEs
Median (IQR)	0 (1.00)	1.00 (1.00)	0.295
ACT scores
Mean (SD)	17.09 (5.09)	18.88 (3.67)	0.225
Well-controlled asthmaa, no. (%)	9 (39.13)	8 (47.06)	0.621
Sinus CT Lund-Mackay score
Median (IQR)	17.00 (7.00)	18.00 (3.00)	0.611
Lung Function
FEV1/FVC, % [mean (SD)]	71.10 (10.35)	66.51 (12.53)	0.213
FEV1%pred, % [mean (SD)]	82.40 (20.38)	73.61 (19.38)	0.177
Total ESS events, median (IQR)	0 (0.50)	0 (1.00)	0.818
ICS doseb, μg/d
Median (IQR)	640.00 (320.00)	640.00 (320.00)	0.690
NCS, no. (%)	17.00 (73.91)	14.00 (82.35)	0.406

Notes: Data are presented as the mean (SD), median (IQR), or n (%), as indicated. P values are for between-group comparisons at baseline (omalizumab add-on vs standard care). ^aWell-controlled asthma was defined as ACT ≥20. ^bICS dose based on daily budesonide equivalent dosage.

Abbreviations: ACT, asthma control test; AEs, Acute exacerbations; BMI, body mass index; CRSwNP, chronic rhinosinusitis with nasal polyps; ESS, endoscopic sinus surgery; ICS, inhaled corticosteroid; IQR, interquartile range; NCS, intranasal corticosteroids; SD, standard deviation.

Clinical Effectiveness

After 52 weeks, compared with the standard care group, the omalizumab add-on group demonstrated superior outcomes across multiple clinical domains (Table 2).

Table 2.

Clinical Outcomes After 52 Weeks of Follow-Up

Clinical Outcome	Omalizumab Add-On Group (n=23)	Standard Care Group (n=17)	P value
Asthma Control
Total no. of AEs	14	20
Median (IQR)	0 (1)	1 (2)	0.037
Mean (SD)	0.61 (1.08)	1.18 (1.07)
Patients with ≥1 AE, no. (%)	8 (34.78)	12 (70.59)	0.027
ACT score, median (IQR)	24.00 (3.00)	23.00 (4.00)	0.157
ACT score, mean (SD)	22.78 (3.20)	21.94 (2.95)
Best ACT score, median (IQR)	25.00 (1.00)	24.00 (3.00)	0.029
Maximum ACT improvement from baseline, mean (SD)	7.52 (4.90)	4.47 (2.83)	0.018
Well-controlled asthmaa, no. (%)	20 (86.96)	13 (76.47)	0.394
Sinonasal Outcomes
Total ESS events, no. (%)	2 (8.70)	7 (41.18)	0.016
Sinus CT Lund-Mackay score, median (IQR)	12.92 (2.50)	18.00 (0)	<0.001
Sinus CT Lund-Mackay score, mean (SD)	12.98 (4.00)	18.18 (2.19)
Medication-Sparing Effects
SCS use, no. (%)	9 (39.13)	11 (64.71)	0.1
ICS daily doseb, μg/d [median (IQR)]	160.00 (520.00)	640.00 (320.00)	0.072
Change of ICS daily doseb, μg/d [median (IQR)]	−160 (400)	0 (160)	0.201
No use or low dose of ICSc, no. (%)	16 (69.57)	7 (41.18)	0.110
Medium dose of ICSc, no. (%)	6 (26.09)	10 (58.82)
High dose of ICSc, no. (%)	1 (4.35)	0
NCS use, no. (%)	13 (56.52)	14 (82.35)	0.082
Antibiotics use, no. (%)	10 (43.48)	12 (92.31)	<0.001
Duration of antibiotic use, days [median (IQR)]	0 (8.5)	23.00 (24.00)	<0.001

Notes: Data are presented as the mean (SD), median (IQR), or n (%), as indicated. P values are for between-group comparisons at week 52 (omalizumab add-on vs standard care). ^aWell-controlled asthma was defined as ACT ≥20. ^bICS dose based on daily budesonide equivalent dosage. ^cICS dose classification based on daily budesonide equivalent doses: No use or low ≤400 μg; medium >400–800 μg; and high >800 μg.

Abbreviations: ACT, asthma control test; AEs, Acute exacerbations; ESS, endoscopic sinus surgery; ICS, inhaled corticosteroid; IQR, interquartile range; NCS, intranasal corticosteroids; SCS, systemic corticosteroids; SD, standard deviation.

Exacerbations

Compared with the standard care group, the omalizumab add-on group experienced fewer acute exacerbations at follow-up (median 0 [IQR 1.00] vs 1.0 [IQR 2.00]; P =0.037). Consistent with this frequency reduction, the proportion of patients who experienced at least one exacerbation event during the 52-week period was significantly lower in the omalizumab cohort (34.78% vs 70.59%; P = 0.027),

Asthma Control

With respect to symptom control, both groups demonstrated longitudinal improvements in ACT scores over the 52-week study period. Compared to the standard care group, the omalizumab add-on group achieved a significantly higher best ACT score (median 25.0 [IQR 1.00] vs 24.0 [IQR 3.00]; P = 0.029) and higher maximum improvement —defined as the net delta change from baseline to the best achieved ACT score (mean 7.52 [SD 4.90] vs 4.47 [SD 2.83]; P = 0.018). Although cross-sectional ACT scores at week 52 did not differ significantly between groups (P = 0.157), the final proportion of patients who achieved well-controlled asthma (ACT ≥20) increased and was numerically greater in the omalizumab add-on group (86.96% vs 76.47%).

Sinonasal Outcomes

A marked improvement in objective sinonasal outcomes was observed. Compared with the standard care group, the requirement for ESS was significantly lower in the omalizumab add-on group (8.70% vs 41.18%; P = 0.016) during the study period. Furthermore, this clinical benefit was corroborated by radiographic evidence, as the omalizumab add-on group had significantly lower sinus CT Lund–Mackay scores at follow-up (median 12.92[IQR 2.50] vs 18.00[IQR 0]; P < 0.001).

Medication Sparing Effect

Omalizumab demonstrated a substantial steroid-sparing and antibiotic-sparing effects over the 52-week period. The proportion of patients requiring systemic corticosteroids was numerically lower in the omalizumab add-on group than in the standard care group (39.13% vs 64.71%; P = 0.1). Regarding maintenance therapies, the de-escalation of ICS reliance was statistically comparable between the two groups over the 52-week period. The absolute change in daily ICS dosage from baseline did not differ significantly between the omalizumab add-on and standard care groups (median −160 [IQR 400] vs 0 [IQR 160]; P = 0.201). Similarly, the number of patients who successfully stepped down to low-dose ICS or discontinued ICS use entirely was statistically similar between the cohorts (n = 6 vs n = 4; P = 0.730). A similar favorable trend was observed in NCS prescription rates (56.52% vs 82.35%, P = 0.082) and antibiotic prescription rates (43.48% vs 92.31%, P < 0.001). Furthermore, omalizumab exhibited a profound protective effect against respiratory infections: the antibiotic prescription rate was markedly lower (43.5% vs 92.3%; P < 0.001), and the overall duration of antibiotic exposure was significantly shorter compared with standard therapy (median 0.0 [IQR 8.5] vs 23.0 [IQR 24.0] days; P < 0.001).

Direct Cost Comparison

Over the 52-week follow-up, the median total direct medical costs were significantly higher in the omalizumab add-on group than in the standard care group (¥44,681.09 [IQR 47,780.91] vs ¥6282.25 [IQR 16,179.90]; P < 0.0001) (Table 3). This difference was driven primarily by overall medication expenditures (mean ¥39,498.49 [SD 21,675.26] vs ¥4003.38 [SD 2077.41]; P < 0.0001), with biologic acquisition costs (mean ¥35,106.26 [SD 20,096.42]) constituting the vast majority of total expenses in the omalizumab cohort. Costs related to systemic corticosteroids were minimal and comparable between the groups (P = 0.615).

Table 3.

Breakdown of Annual Direct Medical Costs per Patient Over 52 Weeks

Cost Category, (CNY ¥)	Omalizumab Add-On Group (n=23)	Standard Care Group (n=17)	P value
Total costs, median (IQR)	44,681.09 (47,780.91)	6282.25 (16,179.90)	<0.0001
Medication costs, mean (SD)	39,498.49 (21,675.26)	4003.38 (2077.41)	<0.0001
Biologic costs, mean (SD)	35,106.26 (20,096.42)	0 (0)	<0.0001
Systemic steroid costs, median (IQR)	0 (50.34)	0 (49.52)	0.615
Antibiotic-related costs, median (IQR)	0 (207.76)	245.70 (289.05)	0.010
Outpatient visit/consultation, median (IQR)	1418.50 (799.50)	1086.00 (1568.00)	0.036
Inpatient care costs, median (IQR)	0 (0)	0 (14,344.95)	0.243
Surgery procedure costs, median (IQR)	0 (0)	0 (14,344.95)	0.197
Nursing and clinical service costs, median (IQR)	0 (0)	0 (435.00)	0.183
Laboratory and diagnostic costs, median (IQR)	1484.60 (2540.58)	2200.42 (2656.43)	0.223

Notes: All costs are expressed in Chinese yuan (¥). The median and IQR are used for descriptive statistics because of the skewed distribution of the cost data.

Abbreviation: IQR, interquartile range.

Additionally, outpatient visit and consultation costs were significantly higher in the omalizumab add-on group (median ¥1418.50 [IQR 799.50] vs ¥1086.00 [IQR 1568.00]; P = 0.036). In contrast, meaningful cost offsets were observed across several categories of healthcare resource utilization, corroborating the clinical and medication-sparing benefits of omalizumab. Antibiotic-related costs were significantly reduced in the omalizumab add-on group (median ¥0 [IQR 207.76] vs ¥198.72 [IQR 289.05]; P = 0.010). Numerical reductions that did not reach statistical significance were also observed in costs related to systemic corticosteroids, inpatient care, laboratory and diagnostic care in the omalizumab add-on group.

Cost-Effectiveness Analysis

In the base-case analysis, when the original observed costs were used, omalizumab add-on therapy was more effective at an increased cost than standard therapy. ICERs were calculated on the basis of a mean incremental cost of ¥36,607.59 (95% CI: ¥25,153.86 to ¥49,648.78). Combining this with the clinical outcomes, the base-case ICER for the reference originator was ¥64,223.84 per acute exacerbation avoided and ¥114,398.72 per ESS avoided (Table 4).

Table 4.

Incremental Cost-Effectiveness Ratio (ICER) of the Omalizumab Add-on and Standard Care Groups

Clinical Outcomes	Omalizumab Add-On Group	Standard Care Group	ΔCost (¥) [95% CI]	ΔEffectiveness [95% CI]	ICER (¥/Event Avoided)
Acute exacerbations (episodes/year)	0.61	1.18	36,607.59 [25,153.86, 49,648.78]	−0.57 [−1.17, 0.067]	64,223.84
ESS (events/year)	0.09	0.41	36,607.59 [25,153.86, 49,648.78]	−0.32 [−0.58, −0.066]	114,398.72

Notes: Incremental cost-effectiveness ratios (ICERs) were calculated as follows: ICER = ΔCost/ΔEffectiveness, where ΔCost represents the difference in direct medical costs between groups (omalizumab minus standard therapy), and ΔEffectiveness represents the corresponding difference in effectiveness for each indicator. The 95% CIs for ΔCost and ΔEffectiveness were derived from 1,000 nonparametric bootstrap iterations. Negative values in ΔEffectiveness indicate a reduction in the occurrence of clinical events (exacerbations or ESS) in the omalizumab add-on group compared to the standard care group.

Abbreviations: CI, confidence interval; ESS, endoscopic sinus surgery; ICER, incremental cost-effectiveness ratio.

Scenario Analysis: Impact of Biosimilar Introduction

The scenario analysis demonstrated that stepwise price reductions radically altered the cost-effectiveness profile based on current institutional procurement databases (Table 5). Compared to the baseline study-period price (S0), applying the 2026 NRDL price (S1) decreased the ICERs to ¥53,072.17 per AE avoided and ¥94,534.81 per ESS avoided.

Table 5.

Scenario Analyses Reflecting Dynamic Pricing and the Impact of Biosimilar on Cost-Effectiveness

Scenario	Product	Unit Price (¥/150mg)	Price Reduction from Study Baseline	Total Cost in Biologic Group [¥, Median (IQR)]	ICER (¥/AE Avoided)	ICER (¥/ESS Avoided)
S0	Originator omalizumab (study-period price)	1204.00	0%	44,681.09 (47,780.91)	64,223.84	114,398.72
S1	Originator omalizumab (2026 NRDL price)	986.00	18.11%	38,254.07 (455,64.32)	53,072.17	94,534.81
S2	Omalizumab alpha	900.00	25.25%	35,718.64 (44,446.32)	48,672.89	86,698.59
S3	Omalizumab biosimilar	788.00	34.55%	31,694.73 (41,458.41)	42,943.60	76,493.28

Notes: Incremental cost-effectiveness ratios (ICERs) were calculated as follows: ICER = ΔCost/ΔEffectiveness, where ΔCost represents the difference in direct medical costs between groups (omalizumab minus standard therapy), and ΔEffectiveness represents the corresponding difference in effectiveness for each indicator. The total direct medical cost in the standard care group remained constant at ¥12,326.22 across all scenarios. Because clinical efficacy is assumed to be equivalent among the originator and its biosimilars, the incremental effects (ΔEffectiveness) remained constant across all scenarios: −0.57 (95% CI: −1.17 to 0.067) for avoiding acute exacerbations, and −0.32 (95% CI: −0.58 to −0.066) for avoiding ESS. Scenarios were defined as follows: S0, originator omalizumab at the study-period price (¥1204.00/150 mg); S1, originator omalizumab at the 2026 NRDL price (¥986.00/150 mg); S2, omalizumab alfa, domestic biosimilar (¥900.00/150 mg); S3, omalizumab biosimilar (¥788.00/150 mg). The 95% confidence intervals for costs were derived from 1000-iteration nonparametric bootstrap resampling.

Abbreviations: AE, acute exacerbations; CI, confidence interval; ESS, endoscopic sinus surgery; ICER, incremental cost-effectiveness ratio; IQR, interquartile range; NRDL, National Reimbursement Drug List.

Furthermore, substituting the reference originator with domestic biosimilars significantly improved economic viability. Under Scenario 3 (¥788.00), representing a 34.55% reduction in unit drug acquisition costs, the ICERs plummeted to ¥42,943.60 for avoiding one AE and ¥76,493.28 for avoiding one ESS. However, it is crucial to note that despite this significant downward shift of approximately 33%, the revised ICERs remain strictly higher than the predefined WTP thresholds. This indicates that while biosimilars markedly improve economic viability, a complete direct cost-offset is still mathematically unachievable under the current pricing structure.

Sensitivity Analysis

For the brand-name drug (Scenario 0), the cost-effectiveness plane (Figure 2A and C) confirmed that omalizumab is a “more effective but more expensive” strategy, as 100% of the bootstrap iterations for all four effectiveness indicators—annual AEs and ESS times— were in the northeast quadrant. The CEACs (Figure 2B and D) indicated that when the WTP threshold was set to the actual treatment costs (¥1745.73 for AE and ¥19,431.92 for ESS), the probability of omalizumab being cost-effective was near 0%. The reference therapy reached a 50% probability of being cost-effective only when the macroeconomic WTP thresholds were elevated to approximately ¥90,000 per AE avoided and ¥115,000 per ESS avoided.

Figure 2.

Probabilistic sensitivity analysis of the reference originator omalizumab (Scenario 0). (A) Scatter plot of the incremental cost-effectiveness ratios for acute exacerbations (AE) avoided; (B) Cost-effectiveness acceptability curve (CEAC) illustrating the probability of the originator strategy being cost-effective across varying willingness-to-pay (WTP) thresholds for AE avoided; (C) Scatter plot for endoscopic sinus surgeries (ESS) avoided; (D) CEAC for ESS avoided over a 52-week horizon. The solid red vertical lines in the CEACs and the solid Orange lines in the scatter plots represent the predefined, event-driven cost-offset WTP thresholds (¥1745.73 for AE and ¥19,431.92 for ESS). The 95% confidence ellipses are shaded in blue in the scatter plots.

Abbreviations: AE, acute exacerbation; CEAC, cost-effectiveness acceptability curve; ESS, endoscopic sinus surgery; WTP, willingness-to-pay.

When the PSA was extended to the biosimilar pricing scenarios, identical structural trends were observed regarding the absolute cost-offset limit, but with markedly improved macroscopic economic viability (Figure 3 and Supplementary Figures S1–S2). Under the most affordable scenario (Scenario 3), all 1000 bootstrap iterations robustly remained in the northeast quadrant (Figure 3A and C). While the probability of achieving cost-effectiveness at the strict event-driven WTP thresholds (¥1745.73 and ¥19,431.92) remained 0%, the introduction of biosimilar pricing substantially shifted the CEACs leftward. Specifically, the 50% probability inflection point plummeted to approximately ¥70,000 for both avoiding one AE and avoiding one ESS (Figure 3B and D). This demonstrates that while a direct short-term cost-offset is not completely achieved, the integration of biosimilars significantly accelerates the probability of economic viability under broader societal thresholds.

Figure 3.

Probabilistic sensitivity analysis of the optimal biosimilar scenario (Scenario 3). (A) Scatter plot of the incremental cost-effectiveness ratios for acute exacerbations (AE) avoided; (B) Cost-effectiveness acceptability curve (CEAC) illustrating the probability of the biosimilar add-on strategy being cost-effective across varying willingness-to-pay (WTP) thresholds for AE avoided; (C) Scatter plot for endoscopic sinus surgeries (ESS) avoided; (D) CEAC for ESS avoided over a 52-week horizon. The solid red vertical lines in the CEACs and the solid Orange lines in the scatter plots represent the predefined, event-driven cost-offset WTP thresholds (¥1745.73 for AE and ¥19,431.92 for ESS). Notably, the CEACs demonstrate a substantial leftward shift compared to the baseline scenario, crossing the 50% probability inflection point at a significantly lower WTP threshold of approximately ¥70,000.

Abbreviations: AE, acute exacerbation; CEAC, cost-effectiveness acceptability curve; ESS, endoscopic sinus surgery; WTP, willingness-to-pay.

Discussion

This real-world study evaluated the clinical effectiveness and cost-effectiveness of omalizumab as an add-on therapy for patients with concomitant asthma and CRSwNP in China. Our findings demonstrate that while omalizumab achieves superior clinical control for comorbid asthma and CRSwNP, it fails to provide direct economic benefit. The 7-fold higher medical expenditure relative to standard therapy (¥44,681.09 vs ¥6282.25) is not offset by the savings from reduced clinical events over a 52-week horizon, rendering it a highly effective but financially nonbeneficial strategy in the short term. However, our dynamic scenario analyses reveal a critical trajectory: as drug acquisition costs decrease via the introduction of biosimilars, the likelihood of achieving cost-effectiveness significantly improves, offering a viable pathway for future clinical application.

The significant clinical gains observed in our study underscore the validity of the UAD concept. By targeting IgE-mediated inflammation, omalizumab simultaneously addressed both upper and lower airway pathologies, for which standard site-specific therapies are often lacking. Our findings align with those of randomized trials and real-world studies, which reported substantial improvements in anti-IgE therapy in terms of acute exacerbations, upper airway control, ESS times and medication step-down in patients with CRSwNP and comorbid asthma.^31,49–52 Notably, regarding asthma symptom dynamics, while the cross-sectional ACT scores evaluated precisely at week 52 did not differ significantly between cohorts, the omalizumab add-on group achieved a significantly higher maximum absolute ACT score (median 25.0 vs 24.0; P = 0.029) and a profound net improvement from baseline (mean 7.52 vs 4.47; P = 0.018). This discrepancy highlights the inherent volatility of UAD. Unlike patients with asthma alone achieved sustained improvements in the ACT score at 4 months, which persisted for more than 12 months.^40,53 UAD patients exhibit dynamic fluctuations in symptom control driven by cross-airway inflammatory interactions.^54,55 To properly contextualize these longitudinal fluctuations, it is crucial to examine published real-world cohorts evaluating mid-to-long-term clinical parameters.^56,57 While continuous therapy yielded progressively higher ACT scores over 36 months, patients who achieved a robust initial response and subsequently discontinued therapy still maintained a significant symptom buffer, with benefits persisting one year after suspension.⁵⁸ Therefore, achieving a higher ceiling of peak clinical control grants UAD patients a greater physiological buffer against exacerbations, suggesting that prolonged, longitudinal maintenance therapy and step-down protocol are required to sustain disease remission.^59,60

Despite these clinical successes, the baseline economic analysis reveals a stark health economics paradox. The ICERs for avoiding a single acute exacerbation (¥64,223.84) and avoiding one ESS event (¥114,398.72) substantially exceed the actual average treatment costs for these events in our cohort. Consequently, the CEACs indicate a 0% probability of the reference originator omalizumab being cost-effective at these strict, event-driven WTP thresholds. This aligns with global findings, where biologics frequently yield high ICERs (eg, in the US, UK and Canada) unless ex-factory prices are aggressively negotiated, as seen in certain European contexts.^36,61–63 Conversely, biologics have demonstrated favorable cost-effectiveness in Italy, largely driven by specifically negotiated ex-factory pricing and higher local costs of standard disease management.⁶⁴ In China, the direct costs of medical services (eg, inpatient care, ESS, and routine exacerbation management) are relatively low. Consequently, the 7-fold higher medical expenditure relative to standard therapy (¥44,681.09 vs ¥6282.25) was driven almost entirely by drug acquisition costs which disproportionately inflates the ICER, rather than general medical services. Recently, the National Medical Products Administration (NMPA) approved omalizumab biosimilars, fundamentally altering the therapeutic landscape in China. To address this dynamic market, our scenario analyses explicitly modeled the anticipated 15–35% price erosion introduced by biosimilars. Strikingly, substituting the originator with the lowest-priced domestic biosimilar substantially reduced the ICERs to ¥42,943.60 and ¥76,493.28, respectively. Even with a 34.55% price erosion introduced by the biosimilar, the therapy remains financially nonbeneficial when strictly benchmarked against the low cost of medical services in China. However, CEACs reveal a highly promising trajectory: the biosimilar add-on therapy achieves a 50% probability of being cost-effective when the WTP threshold reaches approximately ¥70,000. It is notably lower than China’s macroeconomic threshold of 1x per capita GDP. This demonstrates that while the reference originator struggles to achieve cost-effectiveness, the integration of newly approved, affordable biosimilars provides a highly viable and realistic economic pathway for UAD management.

Furthermore, focusing only on short-term direct medical costs underestimates the true overall value of biologics. In our study, omalizumab exhibited a profound and highly significant antibiotic-sparing effect (median duration 0.0 vs 23.0 days; P < 0.001). Beyond mitigating the escalating global health threat of antimicrobial resistance, this drastic reduction in infectious episodes translates directly into latent economic value. As Accordini et al reported, indirect costs constitute 62.5% of Europe’s annual asthma-related expenditures (€19.3 billion).⁶⁵ The incorporation of potential indirect cost savings and long-term complication prevention would likely yield a far more favorable economic profile.

To translate our economic and clinical findings into daily practice and achieve the proposed optimization of cost-effectiveness, it is imperative to define exactly how clinicians should profile and select high-responder or high-burden phenotypes. Chronic airway diseases are highly heterogeneous disorders encompassing diverse immunopathological endotypes and shift to an endotype-based “treatable traits” approach to address unmet clinical needs.^66,67 The routine application of non-invasive T2-high inflammatory biomarkers—specifically serum total IgE, blood or tissue eosinophils, and fractional exhaled nitric oxide (FeNO)—is crucial for predicting treatment response.⁶⁸ These accessible biomarkers accurately reflect the underlying type 2 airway inflammation, effectively translating complex UAD pathologies into identifiable, treatable traits. By utilizing this biomarker-driven strategy to screen for the target population, physicians can precisely tailor biologic therapies like omalizumab. This approach not only maximizes therapeutic efficacy and the likelihood of clinical remission but also ensures the judicious allocation of finite healthcare resources.

Several limitations must be acknowledged. Primarily, the single-center design and exploratory small sample size (n=40) inherently limit the external validity of our conclusions. More importantly, the non-randomized, real-world observational design introduces a significant risk of selection bias. Treatment allocation was not blinded but was heavily driven by the patient’s willingness and financial ability to pay out-of-pocket for expensive biologics. Consequently, these findings should be interpreted as preliminary and hypothesis-generating. Second, the 52-week observational period may not adequately capture the long-term cost offsets derived from minimizing systemic corticosteroid toxicity and preventing revision surgeries. Third, our CEA was conducted exclusively from a healthcare provider perspective, thereby omitting indirect societal costs such as productivity loss—a recognized burden in United Airway Disease. Incorporating these parameters into future models would likely yield a lower ICER, offering a more comprehensive assessment of the biologic’s economic utility. Therefore, future research should prioritize large-scale, multicenter pragmatic trials to validate these exploratory benchmarks. Furthermore, extending cost-utility analyses to include indirect costs and long-term patient-reported outcomes will be essential to accurately inform value-based pricing and reimbursement strategies in China.

Conclusion

In conclusion, omalizumab add-on therapy provides superior clinical benefits for patients with comorbid asthma and CRSwNP. However, at its current price point, omalizumab does not demonstrate cost-effectiveness compared to standard therapy over a 52-week horizon. Optimizing the cost-effectiveness of this biologic strategy requires a dynamic, multi-faceted approach. Future multicenter pragmatic trials and pharmacoeconomic analysis must routinely incorporate head-to-head comparisons between originators and available biosimilars. Furthermore, clinical implementation should rely on dynamic value-based pricing and non-invasive T2-high inflammatory biomarkers to precisely target high-burden clinical phenotypes. This ensures finite healthcare resources are allocated to patients gaining the utmost from its profound medication-sparing effects and averted surgeries.

Funding Statement

This work was supported by the Key Clinical Project of Peking University Third Hospital (BYSYZD2023009 to C.Chang), the National Natural Science Foundation of China (grant numbers 82370032 and 82570044 to C.Chang), and Beijing Natural Science Foundation (grant number 7232205 to C.Chang).

Abbreviations

ACT, Asthma Control Test; AEs, Acute exacerbations; CEA, Cost-effectiveness analysis; CEAC, Cost-effectiveness acceptability curve; CI, Confidence interval; CRSwNP, Chronic rhinosinusitis with nasal polyps; CT, Computed tomography; ESS, Endoscopic sinus surgery; ICER, Incremental cost-effectiveness ratio; ICS, Inhaled corticosteroids; IQR, Interquartile range; ISPOR, International Society for Pharmacoeconomics and Outcomes Research; LM, Lund-Mackay; NCS, Intranasal corticosteroids; NMPA, National Medical Products Administration; NRDL, National Reimbursement Drug List; OCS, Oral corticosteroids; SD, Standard deviation; SCS, Systemic corticosteroids; STROBE, Strengthening the Reporting of Observational Studies in Epidemiology; UAD, United airway disease; WTP, Willingness-to-pay.

Data Sharing Statement

The datasets used and analyzed during the current study are available from the corresponding author, Dr. Chun Chang, on reasonable request.

Ethics Approval and Consent to Participate

This study was approved by the Ethics Committee of the Peking University Third Hospital (Approval No. 2024-102-01), and the research was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants before enrollment.

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; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.