Cost-utility analysis of omalizumab for the treatment of chronic spontaneous urticaria in China

Abstract

Background

Chronic spontaneous urticaria (CSU) is a common inflammatory immune skin disease. It has a serious impact on the patients’ quality of life and imposes a serious financial burden on patients. The standard therapy for CSU (using antihistamines), while less costly, has limited efficacy and no longer adequately meets the clinical needs of CSU patients. Omalizumab is the world’s first and currently the only biologic approved for the treatment of CSU. Several studies have confirmed the efficacy and safety of omalizumab for CSU. However, the economics of omalizumab treatment relative to standard therapies remains unknown in China.

Objective

The purpose of this study was to analyze the cost-effectiveness of omalizumab versus standard treatments for CSU after omalizumab’s inclusion in the National Drug Insurance List from the patient’s perspective.

Methods

We developed a Markov model based on the Urticaria Activity Score over 7 days (UAS7). The modeling period was 4 weeks. The time horizon was 10 years. The willingness-to-pay threshold (WTP) of 1–3 times gross domestic product (GDP) per capita was selected. Incremental cost-effectiveness ratio (ICER) was calculated from the base-case analysis, and one-way sensitivity analysis and probabilistic sensitivity analysis were performed.

Results

The ICER of omalizumab treatment relative to standard treatment was ¥160,411/QALY, which was between 1 and 3 times GDP per capita. Sensitivity analyses illustrated that the direct cost of omalizumab had a significant effect on the ICER and demonstrated the stability of the results.

Conclusions

Omalizumab treatment is a cost-effective regimen compared with standard therapy under certain circumstances. This demonstrates the important role that health insurance policies play in reducing the burden on CSU patients. However, the limitations of applying foreign clinical data in this paper and the uncertainty of cost-effectiveness at a low WTP threshold are two aspects that cannot be ignored, and subsequent related studies are needed. This study will help patients to make decisions about treatment options, and will be a reference to relevant healthcare organizations.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12962-025-00643-7.

Introduction

As a common clinical skin disease, urticaria is a disorder characterized by recurrent episodes of itchy, transient, erythematous wheals with or without angioedema [1]. Clinically, urticaria with a duration of more than 6 weeks is called chronic urticaria. Chronic urticaria can be categorized into chronic induced urticaria and chronic spontaneous urticaria (CSU) based on the presence or absence of an identifiable causative agent. The prevalence of CSU is 0.5-1% of the total population [2]. In China, the incidence rate of CSU is approximately 1.5% [3]. The pathogenesis of CSU is complex and remains unexplored. Meanwhile, CSU can seriously affect the quality of life of patients, which brings great psychological and economic burdens to patients and their families [4].

For the treatment of CSU, the 2021 edition of the international guidelines recommends the use of conventional doses of second-generation H₁ antihistamines as the first-line treatment option for CSU (standard of care). If the efficacy of the conventional dose does not meet expectations, the dose may be increased up to fourfold. If the 4-fold dose regimen still fails to control symptoms, the second-line treatment will be progressed, with the primary drug called omalizumab [5]. Omalizumab is the world’s first and currently only biologic approved for CSU treatment. As an anti-Immunoglobulin E (anti-IgE) humanized monoclonal antibody, omalizumab accurately blocks the IgE-Recombinant receptor I for the Fc region of Immunoglobulin E (FcεRI) pathway by binding to free IgE in the patient’s body and down-regulating the FcεRI receptor on the surface of the mast cell, thereby inhibiting mast cell activation and mediator release and the process of inflammatory mediator release [6]. Up to now, a number of phase III clinical studies around the world have shown that omalizumab has good efficacy and safety in the treatment of CSU [7–10]. Compared to standard therapy, omalizumab has a superior performance in treating CSU [9, 11].

CSU has a huge impact not only on the patients themselves but also on the productivity of the society due to its specific onset of symptoms and relatively long duration [2]. The high cost of omalizumab, a powerful option for the treatment of CSU, remains a factor that cannot be ignored. From March 1st, 2023, a new version of China’s National Health Insurance Drug List has been implemented, which includes the indication of omalizumab for CSU. Currently, there have been several economic evaluations of omalizumab for the treatment of CSU globally [12, 13], but there are no studies in China in this area. The economics of omalizumab for CSU after inclusion in the medical insurance drug catalog needs to be further studied. Considering the impact of CSU on patients and their families, we will conduct the research according to the condition. Therefore, we have chosen the patient’s perspective to judge the resource consumption and obtained effects brought by the intervention measures to patients and their families. The purpose of this research is to determine the economics of using omalizumab and traditional treatment regimens from the patient’s point of view in China, and to provide a reference for healthcare organizations to make relevant decisions.

Methods

Target population

The base-case analysis for this study considered patients with moderate and severe CSU who were recruited in the GLACIAL phase III randomized controlled trial and were not efficacious through standard therapy [10]. This population was considered representative for modeling purposes.

Perspective

The purpose of this paper is to investigate whether omalizumab treatment is a more cost-effective option for patients after inclusion in the Medicare catalog, and therefore patients were chosen as the study perspective for this report.

Interventions and comparators

A continuous standard of care (SoC) regimen was chosen for this study, specifically consisting of 4-fold dose of antihistamines and/or leukotriene receptor antagonists. SoC plus placebo comprised the control regimen [10]. In contrast, the intervention regimen consisted of SoC and omalizumab. The rationale for introducing the control group was based on clinical feedback from the GLACIAL trial, which showed that CSU not effectively controlled by SoC could still continue to be treated with SoC due to the lack of other licensed options before the approval of omalizumab [12]. In this study, omalizumab was dosed at 300 mg in all cases and administered subcutaneously. Omalizumab was administered every 4 weeks. The SoC regimen was oral administration of loratadine (a typical second-generation H1 antihistamine). The dose administered was 40 mg a day.

Model structure

In this study, a Markov model was used, and the model structure was performed using previous studies as a reference [12, 13]. The model diagram is shown in Fig. 1. Health status was judged based on the Urticaria Activity Score over 7 days (UAS7). The UAS7 measured urticaria over a 7-day period by means of a daily record. Scores ranged from 0 to 42 and the model was categorized into a total of 5 disease states to reflect different levels of disease activity: “urticaria-free (0)”, “well-controlled urticaria (1–6)”, “mild urticaria (7–15)”, “moderate urticaria (16–27)” and “severe urticaria (28–42)”. Some studies have already shown that the UAS7 score is a valid way to characterize the health status of the CSU [12, 13]. In addition to the above five states, there are three additional states, namely the “relapse” state, the “spontaneous remission” state, and the “death” absorption state. The “relapse” state and the “spontaneous remission” state are collections of several state transfers. The “relapse” state includes the transferring of patients in the “urticaria-free”, “well-controlled urticaria” and “mild urticaria” states, respectively to the “moderate urticaria” and “severe urticaria” states. The “spontaneous remission” includes the transferring of patients in the “well-controlled urticaria”, “mild urticaria”, “moderate urticaria”, and “severe urticaria” states, respectively to the “urticaria-free” state.

Fig. 1.

Diagram of the Markov model structure. The transfer process of the patient in different states is presented by arrows in the figure. The state pointed to by the arrow is the state after the transition, and the opposite direction is the state before the transition

The modeling period was set at 4 weeks according to the dosing time characteristics of omalizumab. The initial entry into the model included two states, “moderate urticaria” and “severe urticaria”. According to the previous study, 71% of patients in the SoC group entered the model with “severe urticaria” and 29% with “moderate urticaria”. In the OMA group, 61.4% of patients entered the model with “severe urticaria” and 38.6% with “moderate urticaria” [12]. After the initial treatment, patients in these two states could change to any of the five UAS7 states. The time frame chosen for this study was 10 years. The literature suggested that no major studies providing estimates of the probability of remission beyond 10 years had been identified [12]. Also, according to clinical experts, 10 years covered the cost and effectiveness of all treatments [13]. Because changes in the state of a patient may occur at any time during a cycle, we corrected the model for half-cycling in order to more accurately simulate the process of state transfer in patients.

The Markov model in this study was performed in Treeage Pro2022, a professional decision tree and cost-utility analysis software used in various industries such as healthcare. In addition, the content presented in section “2.7 Sensitivity analysis” was also done by this software.

Costs, utility values, and transfer probability data

This paper was based on the patient’s point of view, therefore costs mainly included all direct medical cost, direct non-medical cost, and indirect cost. Direct cost was derived from official data. Indirect cost in this study, on the other hand, mainly incorporated lost productivity, specifically in terms of the impact of the disease on lost wages, with reference data from the published literature [14]. Values for the probability of transfer between different states were derived from the GLACIAL phase III trial [10, 12]. Utility values for each of the five health states were based on published research [12, 15]. Specifically, the study was a mixed-effects regression model constructed from pooled EQ-5D data from the GLACIAL, ASTERIA I, and ASTERIA II trials [15]. The cost and utility values are summarized in Tables 1 and 2, and the transfer probabilities are summarized in the Supplementary Material. For the transfer probability values of the other states to the “Death” state, we used the officially published natural mortality rate of 7.4‰ for the Chinese population in 2022. In terms of adverse effects, we did not find specific data on the reduction in utility value due to adverse effects of the two drugs, and therefore, the additional cost and reduction in utility value due to adverse effects were not considered in this study. The lack of this data is very likely to lead to an overestimation of the net utility of the omalizumab treatment group.

Table 1.

Cost inputs. URT: urticaria

Cost	Cost value	Distribution	Source
Omalizumab cost(¥/300 mg)	357.6	gamma	www.menet.com
Loratadine cost(¥/60 mg)	8.8	gamma	www.menet.com
Injection cost (¥/time)	6.3	gamma	www.yaozh.com
Average annual wage of	65,237		www.baijiahao.baidu.com
Chinese people (¥/In 2022)
Loss of productivity in “URT free” state (%)	3.3		[14]
Loss of productivity in “well-controlled URT” state (%)	3.6		[14]
Loss of productivity in “mild URT” state (%)	5.5		[14]
Loss of productivity in “moderate URT” state (%)	6.8		[14]
Loss of productivity in “severe URT” state (%)	7.7		[14]

Table 2.

Utility inputs

Markov state	Utility value	Distribution	Source
urticaria free	0.897	beta	[12, 15]
well-controlled urticaria	0.859	beta	[12, 15]
mild urticaria	0.845	beta	[12, 15]
moderate urticaria	0.782	beta	[12, 15]
severe urticaria	0.712	beta	[12, 15]

Model outputs

The health output indicator for this study is quality-adjusted life years (QALYs). This metric is a standardized, generic health output metric that indicates the number of years a patient survives in perfect health. To capture the difference in cost per unit of utility between the two treatment regimens, we used the incremental cost-effectiveness ratio (ICER), which is obtained by dividing the increased cost of the omalizumab treatment group relative to the SoC treatment group by the increased QALY value. We used 1–3 times the World Health Organization’s recommended gross domestic product (GDP) per capita as the willingness-to-pay threshold. In 2022, China’s GDP per capita was ¥85,698. According to the China Pharmacoeconomics Evaluation Guidelines (2020 edition), a discount rate of 5% was applied for cost as well as utility in this study.

Sensitivity analysis

We used one-way sensitivity analysis and probabilistic sensitivity analysis (PSA), respectively. The former is designed to detect the effect of a single parameter on ICER. The latter, on the other hand, simultaneously assesses the impact of uncertainty in all parameters on the results by performing 1000 random samples of each parameter in the model under different probability distributions, and then presenting the simulation results on the cost-utility plane and plotting the cost-utility acceptable curve. In PSA, the gamma distribution (Table 1) and beta distribution (Table 2) were selected for the cost and utility values respectively [16]. Both sensitivity analyses were able to test the stability of the test results.

Compliance with ethics guidelines

The data related to this study were obtained from related clinical trials and previously published papers. This study did not contain any human or animal related experiments and therefore did not require approval from the Ethics Committee.

Results

Base-case results

The results of the base-case analysis are shown in Table 3. In terms of health outputs, when QALY was used as a measure, the omalizumab group had a QALY value of 6.22, which was significantly higher than the QALY value of the SoC group (6.06). But the omalizumab group also had to bear more costs. The ICER value derived from the deterministic analysis was ¥160,411.52/QALY, a value that lies between 1x GDP per capita (¥85,698/QALY) and 3x GDP per capita (¥257,094/QALY). This suggests that omalizumab is an economical option relative to SoC treatment.

Table 3.

Base-case results. OMA: omalizumab; incr: incremental; eff: effectiveness

Strategy	Cost (¥)	Incr Cost (¥)	Eff (QALY)	Incr Eff (QALY)	ICER (¥/QALY)
SoC	30,850.87		6.06
OMA	56,053.51	25,202.65	6.22	0.16	160,411.52

One-way sensitivity analysis results

In order to test the stability of the results, this study conducted a one-way sensitivity analysis of the key parameters in the model. Specifically, it is presented by adjusting the key parameters upward as well as downward by 10% (the range of variation of the discount rate is 0–8%), and finally the impact of the key parameter changes on the ICER is presented in the form of a tornado diagram (Fig. 2). The graphs are organized in order of magnitude of impact on ICER. The influence of different changes in parameters (increasing or decreasing) on ICER is distinguished by red and blue. The factor with the greatest impact on ICER is the direct cost of omalizumab. As can be seen in the figure, when its value rose by 10%, the ICER value increased by 12.5%. In addition to this factor, the utility values of some disease states as well as the indirect costs of the disease (productivity loss) play an important role in the variation of ICER, which reveals a strong link between chronic spontaneous urticaria and productivity loss.

Fig. 2.

One-way sensitivity analysis of SoC versus OMA treatment regimen. The horizontal axis indicates the ICER value. The vertical axis indicates the individual factors that have an effect on ICER (the higher position indicates a greater degree of influence on ICER). The length of the bar indicates the effect on ICER of changes in ICER parameter values. The red column represents the influence of the increase of the corresponding parameter value on the ICER value, and the blue column represents the influence of the decrease of the corresponding parameter value on the ICER value

Probabilistic sensitivity analysis results

In order to assess the impact of parameter uncertainty on the results, we performed a PSA. we used 1% and 10% of the mean as the estimated range of variation in standard deviation for the cost and utility values, respectively. The simulation results are presented on the cost-effectiveness quadrant plots as shown in Figs. 3 and 4. The x-axis represents the incremental QALY obtained and the y-axis represents the incremental cost. Each point represents one of 1000 simulations. The green dots indicate that the OMA group has cost-effectiveness at the given threshold. The red dots indicate that the OMA group does not have cost-effectiveness at the given threshold. The green ellipse contains the 95% ICER estimate. We have chosen 1 and 3 times the GDP per capita as thresholds for the analysis, respectively. Figures 3 and 4 demonstrated the distribution of the incremental costs as well as the effects for the SoC and OMA groups when the WTP was ¥85,698/QALY and ¥257,094/QALY, respectively. In all simulations, the OMA group obtained an additional cost. In 82.9% of the simulations, the OMA group had additional effects. The average ICER was similar to the results of the deterministic analysis. The cost-effectiveness acceptable curve in Fig. 5 revealed the probability that omalizumab was cost-effective at the given threshold. This probability value increased as the threshold increased. When the WTP was ¥85,698/QALY, the probability of having a cost-effectiveness in the OMA group was 20.3%. This value rose to 68.5% when the WTP was ¥257,094/QALY. We can find that when the WTP is 1 x GDP per capita, the economic advantage of the OMA group is very low, and this advantage gradually increases with the rising of the WTP threshold.

Fig. 3.

Cost-effectiveness plane of SoC group vs. OMA group (WTP = ¥85,698/QALY)

Fig. 4.

Cost-effectiveness plane of SoC group vs. OMA group (WTP = ¥257,094/QALY)

Fig. 5.

Cost-effectiveness acceptability curve. The X-axis represents the WTP value (ranging from 1 x GDP per capita to 3 x GDP per capita), and the Y-axis represents the probability that the treatment plan has cost-effectiveness

Discussion

CSU is a common clinical condition in dermatology, which often recurs and has a long duration, seriously affecting patients’ life, work, socialization, and psychological status. They are manifested by decreased sleep quality, social fears, anxiety, and depression. In addition, more than 30% of patients have missed work due to their condition [17, 18]. It is also important to note that CSU patients are 4.68 times more likely to have a combination of different types of allergic diseases such as allergic rhinitis, asthma and atopic dermatitis than non-CSU patients [19, 20]. The burden of disease is even greater in patients with comorbidities.

The most common clinical treatment option is the use of antihistamines, which can control symptoms to some extent. However, antihistamines do not adequately meet the therapeutic needs of patients. Studies have shown that over 50% of CSU patients are uncontrolled with standard doses of antihistamines; 25–33% of patients are still not effectively controlled when antihistamines increase to four times dose [2]. The emergence of omalizumab has provided a powerful solution to the therapeutic challenge of CSU. In a series of clinical studies for CSU in China and abroad, omalizumab has not only been able to produce rapid efficacy [9, 21], but also demonstrated excellent safety [11, 22].

Outstanding performance in clinical and real-world studies have also elevated the status of omalizumab in national and international CSU guidelines. For example, in the 2021 edition of the European Combined Urticaria Guidelines, omalizumab has been recommended as a second-line therapy for the treatment of patients whose symptoms cannot be effectively controlled by antihistamines for 2–4 weeks [5]. In the latest version of the Chinese urticaria guideline (“Chinese Urticaria Guidelines (2022 Edition)”), omalizumab is recommended as the third-line treatment of choice for patients with chronic urticaria who are unresponsive or intolerant to antihistamine treatment. This undoubtedly provides another crucial option for patients to fight CSU.

In April 2022, omalizumab was formally approved by the National Medical Products Administration (NMPA) for the treatment of “symptomatic adults and adolescents (12 years of age and older) with CSU who remain symptomatic despite treatment with H₁ antihistamines. " Omalizumab, representing an innovative biological agent, will, yet, result in increased treatment expenses. As an important aspect of China’s efforts to reduce the burden of patient care, health insurance policy has been continuously enriched and improved in recent years. And the health insurance policy to some extent solves the problem of expensive price, which is a major shortcoming of omalizumab for CSU treatment. In addition to CSU, many foreign studies have evaluated the economics of omalizumab for the treatment of allergic asthma, with varying results [23–28]. And most studies of omalizumab for CSU have shown economy [12, 13]. The fact that less than a year elapsed between the approval of the indication and its entry into the health insurance shows the great therapeutic potential of omalizumab. Based on the above background, our study investigated whether the inclusion of omalizumab in the health insurance actually brings effective treatment of CSU as well as reduced economic burden to patients.

The results of our study showed that omalizumab treatment for CSU led to additional cost as well as utility with an ICER of ¥160,411/QALY, which was between one and three times GDP per capita. This suggested that omalizumab was a treatment option with cost-utility under certain circumstances. In the one-way sensitivity analysis conducted later (according to the sorting of parameters as well as the length and color of the column), we found that the direct cost of omalizumab was still the most influential factor on the ICER, and its pricing was a key determinant for the economics of the treatment regimen, while the indirect cost of each state (mainly in terms of productivity loss) was also a non-negligible aspect. The relevance of this factor has been previously documented [17, 29, 30]. The subsequent probabilistic sensitivity analysis also gave more theoretical support to the previous conclusions. Meanwhile, we found that when 1 x GDP per capita was used as the WTP threshold, the probability of the OMA group being economically viable was very low (20.3%), and this value increased with the rising of the WTP threshold. The above opinions provided us with two ideas. First, the drug pricing of omalizumab remains the biggest factor affecting its economy. As a result, relevant researchers should evaluate the pricing in all aspects to ensure that the cost of omalizumab and its efficacy can be well matched, so that more patients with poor SoC efficacy will be inclined to use omalizumab. Second, a significant correlation is discovered between CSU and social productivity. This implies that individuals with CSU will mostly benefit from prompt treatment, and that treating them at an early stage will significantly lower the cost of therapy. It cannot be ignored that although the ICER value of the base-case analysis results is within the threshold range, the PSA results reveal uncertainties, especially at lower WTP levels, the economic advantage of OMA is relatively low.

Our study has clear strengths. First, this paper is the first pharmacoeconomic evaluation of omalizumab in the treatment of CSU in China, which will be helpful for subsequent research. Secondly, the content of this study is closely related to the medical insurance policy background. At the same time, the results highlight the important role omalizumab plays in reducing the burden on patients after it is included in medical insurance.

However, the research still has limitations. At first, before the introduction of new policies in 2024, the health insurance reimbursement rates in different regions of China are different. The reimbursement rate of only one region was chosen as the data source in this study, which was a lack of generalization. Secondly, due to the lack of relevant data, the utility values and transfer probability data used in this study were from studies in foreign regions. The utility values and transfer probabilities of different states of CSU in various countries are not the same, which will affect the accuracy of the study to some extent. Moreover, in the PSA of this study, the distribution of costs as well as utilities used mean ± 1% and ± 10%, respectively. The uncertainty of the real situation may be different from what is represented in the PSA of this paper. In the case of costs, we chose to calculate indirect costs through the effect on patient’s wages, which was likely to underestimate the actual values. According to the scope of indirect costs, lost productivity also includes lost wages for the patient’s family members, including time off from school, work, and so on. Furthermore, in this study, other second-generation antihistamines commonly used in clinical practice worldwide were ignored, such as fexofenadine, desloratadine, levocetirizine, cetirizine and bilastine. These drugs may have different therapeutic effects, safety and costs, which is a limitation that cannot be ignored. However, in this research model, only the more commonly used loratadine was included, which may lead to bias in the final results (making the results more inclined towards the omalizumab treatment group). In future research, second-generation antihistamines of this category can be incorporated into the treatment regimens through sensitivity analyses or scenario modeling. Finally, the selection of the distribution of patients’ initial health states in this study was derived from the GLACIAL phase III trial, which may not accurately reflect the actual patient population. Moreover, due to the limitations of the data, the effects of adverse events (such as skin damage, respiratory system damage, etc.) have not been incorporated into the model in this study for the time being, which is very likely to lead to deviations in the final results. We acknowledge that the above limitations may lead to radically different conclusions from having a cost-effectiveness to not having a cost-effectiveness. However, based on the restricted available data, we confirm that all data in this study were obtained from the best accessible sources, minimizing the impact of data bias on arriving at true conclusions.

It is worth noting that although the treatment costs of omalizumab today have a significant decline in the treatment costs and better curative effects, its treatment costs are still expensive compared to SoC. China, as a developing country with a large population base, will still have a significant percentage of patients who cannot bear the burden of treatment with omalizumab. Consequently, we recommend that relevant manufacturers can formulate appropriate patient assistance plans to provide drug assistance to relatively poor patients to improve the accessibility of the drug. At the same time, clinicians should consider the specific situation in the choice of CSU treatment, because omalizumab is not suitable for all CSU conditions, especially children under 12 years old. Therefore, reasonable choice of treatment plan is important. In addition, because China’s economic development is highly unbalanced, the level of economic development between regions is large. As a consequence, different regions should combine the local economic development level when referring to the results of this study. In economically developed areas, such as Beijing and Shanghai (per capita GDP is $27,729 and $26,252, respectively, which exceeded twice the per capita GDP of China [31]), omalizumab will have a higher probability of cost-effectiveness. Conversely, this probability will be reduced in areas where economic development is relatively backward.

In future research, we call for the emergence of more CSU treatment data based on the Chinese background, especially in terms of parameters such as transition probability and health utility value. This is crucial for future economic evaluation and will help the medical department and patients make reasonable and correct decisions.

Conclusions

In summary, from the patient’s perspective, the inclusion of omalizumab in Medicare for the treatment of CSU may be considered cost-effective under certain assumptions. The conclusion will help healthcare organizations as well as patients to make treatment decisions. Considering the limitations of this study and the resulting uncertainty of the model, we urgently need the emergence of data such as utility values and transfer probabilities based on China in the future. They can make the subsequent research results closer to the Chinese situation.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Author contributions

YH participated in the conception and design of the paper, and was responsible for the analysis, interpretation and discussion of the data. HY and ZH revised and finalized the paper. All authors read and approved the final manuscript.

Funding

Not applicable.

Data availability

Data is provided within the manuscript or supplementary information files.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.