奥马珠单抗在合并哮喘与慢性鼻窦炎伴鼻息肉中的临床与成本效果：一项真实世界探索性研究

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中文摘要

目的： 重度哮喘与慢性鼻窦炎伴鼻息肉（CRSwNP）常共存，代表严重的“联合气道疾病”（UAD）表型。尽管奥马珠单抗已分别获批用于这两种疾病，但针对该合并表型的临床和经济可行性的真实世界评估仍有限。我们评估了奥马珠单抗附加治疗在中国成人UAD中的成本效果。
方法： 这项为期52周的探索性研究比较了奥马珠单抗附加治疗（n=23）与标准治疗（n=17）在合并哮喘和CRSwNP患者中的效果。临床结局包括急性加重（AEs）、内镜鼻窦手术（ESS）需求、哮喘控制测试（ACT）评分、鼻窦CT Lund-Mackay（LM）评分、皮质类固醇和抗生素暴露。从医疗保健提供者角度使用2024年不变价格分析成本效果，并通过1000次迭代自举法评估决策不确定性。情景分析评估了最近获批的国产生物类似药的经济影响。
结果： 在第52周，与标准治疗相比，奥马珠单抗附加治疗组在年急性加重次数（中位数0 [IQR 1.00] vs 1.0 [IQR 2.00]；P = 0.037）和ESS率（8.70% vs 41.18%；P = 0.016）方面实现了显著降低。尽管第52周横断面ACT评分相当，但奥马珠单抗显示出更优的峰值疗效，最佳ACT评分更高（中位数25.0 [IQR 1.00] vs 24.0 [IQR 3.00]；P = 0.029），且从基线的最大改善更大（平均7.52 [SD 4.90] vs 4.47 [SD 2.83]；P = 0.018）。奥马珠单抗还产生显著更低的LM评分（中位数12.92 [IQR 2.50] vs 18.00 [IQR 0]；P < 0.001）和显著的抗生素节约效应（中位持续时间0.0 [IQR 8.5] vs 23.0 [IQR 24.0]天；P < 0.001）。总直接医疗费用约高7倍（¥44,681.09 [IQR 47,780.91] vs ¥6282.25 [IQR 16,179.90]；P < 0.0001），主要由生物制剂采购成本驱动。参考原研药的基线增量成本效果比（ICERs）为每避免一次急性加重¥64,223.84和每避免一次ESS ¥114,398.72，在严格的支付意愿阈值下成本效果概率为0%。用最低价国产生物类似药替代原研药后，ICERs大幅降至¥42,943.60和¥76,493.28。
结论： 奥马珠单抗提供了优越的多领域临床控制和显著的抗生素节约效应。虽然参考原研药在中国52周时间范围内以其基线价格不具有成本效果，但通过集中采购逐步降价以及可负担生物类似药的出现提供了高度可行的经济路径。未来优化需要动态的价值导向定价和针对高负担UAD表型。

英文摘要

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.