哮喘患者使用度普利尤单抗与淋巴瘤风险：一项基于人群的队列研究
2025/08/01
摘要
背景：度普利尤单抗（Dupilumab）已被批准用于治疗特应性皮炎、哮喘及其他过敏性疾病。近期研究表明，接受杜匹鲁单抗治疗的特应性皮炎患者发生皮肤淋巴瘤的风险较高。本研究旨在探讨哮喘患者使用杜匹鲁单抗后的淋巴瘤风险。
方法：这项基于人群的队列研究纳入了2018年至2024年间美国开始接受度普利尤单抗或活性对照药物（吸入性糖皮质激素[ICS]联合长效β₂受体激动剂[LABA]，即ICS/LABA）治疗的哮喘患者。研究采用倾向评分匹配（PSM）平衡组间基线特征。主要结局为新发淋巴瘤，次要结局包括其他恶性肿瘤及全因死亡率。
结果：研究共纳入14,936例接受度普利尤单抗治疗和734,126例接受ICS/LABA治疗的哮喘患者。经倾向评分匹配后，度普利尤单抗组患者的淋巴瘤风险更高（54例 vs. 43例，风险比[HR]=1.79，95%置信区间[CI] 1.19–2.71），尤其是T细胞和自然杀伤（NK）细胞淋巴瘤（19例 vs. <10例，HR=4.580，95% CI 1.82–11.53）。其他恶性肿瘤的发生率无显著差异。此外，度普利尤单抗组的全因死亡率显著降低（328例 vs. 793例，HR=0.65，95% CI 0.57–0.74）。
结论：尽管度普利尤单抗治疗可能增加哮喘患者的淋巴瘤风险（特别是T/NK细胞淋巴瘤），但其与更低的全因死亡率相关。这些发现提示，需对度普利尤单抗相关淋巴瘤的免疫学机制开展长期监测及深入研究。
Dupilumab and lymphoma risk among patients with asthma: a population-based cohort study.
Kevin, Sheng-Kai Ma; Bethany,
Abstrast
BACKGROUND: Dupilumab is approved for treatment of atopic dermatitis, asthma and other allergic diseases, including atopic dermatitis. Recent studies suggest that patients with atopic dermatitis receiving dupilumab are at higher risk of developing cutaneous lymphoma. This study aimed to investigate the risk of lymphoma among asthma patients treated with dupilumab.
METHODS: This population-based cohort study included U.S. patients with asthma who initiated dupilumab or the active comparator (combination therapy with inhaled corticosteroids [ICS] plus long-acting beta agonists [LABA], or ICS/LABA), between 2018 and 2024. Propensity score matching was used to balance baseline characteristics between groups. The primary outcome was new-onset lymphoma, and the secondary outcomes were other malignancies and all-cause mortality.
RESULTS: A total of 14 936 dupilumab-treated and 734 126 ICS/LABA-treated asthma patients were included. After propensity score matching, dupilumab-treated patients were found to have a higher risk of lymphoma (n=54 versus 43 cases, hazard ratio [HR]=1.79, 95% CI 1.19, 2.71), especially T and natural killer (NK) cell lymphomas (n=19 versus <10, HR=4.580, 95% CI 1.82, 11.53). There was no significant difference in incidence of other malignant neoplasms.Dupilumab was also associated with significantly lower all-cause mortality (n=328 versus 793, HR=0.65, 95% CI 0.57, 0.74).
CONCLUSION:Dupilumab treatment was associated with lower all-cause mortality among asthma patients despite increased risk of lymphoma, particularly T and NK cell lymphomas. These findings highlight the need for long-term surveillance and further research into the immunological mechanisms underlying dupilumab-associated lymphoma in asthma.
背景：度普利尤单抗（Dupilumab）已被批准用于治疗特应性皮炎、哮喘及其他过敏性疾病。近期研究表明，接受杜匹鲁单抗治疗的特应性皮炎患者发生皮肤淋巴瘤的风险较高。本研究旨在探讨哮喘患者使用杜匹鲁单抗后的淋巴瘤风险。
方法：这项基于人群的队列研究纳入了2018年至2024年间美国开始接受度普利尤单抗或活性对照药物（吸入性糖皮质激素[ICS]联合长效β₂受体激动剂[LABA]，即ICS/LABA）治疗的哮喘患者。研究采用倾向评分匹配（PSM）平衡组间基线特征。主要结局为新发淋巴瘤，次要结局包括其他恶性肿瘤及全因死亡率。
结果：研究共纳入14,936例接受度普利尤单抗治疗和734,126例接受ICS/LABA治疗的哮喘患者。经倾向评分匹配后，度普利尤单抗组患者的淋巴瘤风险更高（54例 vs. 43例，风险比[HR]=1.79，95%置信区间[CI] 1.19–2.71），尤其是T细胞和自然杀伤（NK）细胞淋巴瘤（19例 vs. <10例，HR=4.580，95% CI 1.82–11.53）。其他恶性肿瘤的发生率无显著差异。此外，度普利尤单抗组的全因死亡率显著降低（328例 vs. 793例，HR=0.65，95% CI 0.57–0.74）。
结论：尽管度普利尤单抗治疗可能增加哮喘患者的淋巴瘤风险（特别是T/NK细胞淋巴瘤），但其与更低的全因死亡率相关。这些发现提示，需对度普利尤单抗相关淋巴瘤的免疫学机制开展长期监测及深入研究。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
（Eur Respir J 2025 Jun 19;(0)DOI：10.1183/13993003.00139-2025.IF:12.339）
Dupilumab and lymphoma risk among patients with asthma: a population-based cohort study.
Kevin, Sheng-Kai Ma; Bethany,
Abstrast
BACKGROUND: Dupilumab is approved for treatment of atopic dermatitis, asthma and other allergic diseases, including atopic dermatitis. Recent studies suggest that patients with atopic dermatitis receiving dupilumab are at higher risk of developing cutaneous lymphoma. This study aimed to investigate the risk of lymphoma among asthma patients treated with dupilumab.
METHODS: This population-based cohort study included U.S. patients with asthma who initiated dupilumab or the active comparator (combination therapy with inhaled corticosteroids [ICS] plus long-acting beta agonists [LABA], or ICS/LABA), between 2018 and 2024. Propensity score matching was used to balance baseline characteristics between groups. The primary outcome was new-onset lymphoma, and the secondary outcomes were other malignancies and all-cause mortality.
RESULTS: A total of 14 936 dupilumab-treated and 734 126 ICS/LABA-treated asthma patients were included. After propensity score matching, dupilumab-treated patients were found to have a higher risk of lymphoma (n=54 versus 43 cases, hazard ratio [HR]=1.79, 95% CI 1.19, 2.71), especially T and natural killer (NK) cell lymphomas (n=19 versus <10, HR=4.580, 95% CI 1.82, 11.53). There was no significant difference in incidence of other malignant neoplasms.Dupilumab was also associated with significantly lower all-cause mortality (n=328 versus 793, HR=0.65, 95% CI 0.57, 0.74).
CONCLUSION:Dupilumab treatment was associated with lower all-cause mortality among asthma patients despite increased risk of lymphoma, particularly T and NK cell lymphomas. These findings highlight the need for long-term surveillance and further research into the immunological mechanisms underlying dupilumab-associated lymphoma in asthma.
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