中华皮肤科杂志 ›› 2022, Vol. 55 ›› Issue (6): 486-493.doi: 10.35541/cjd.20220021

• 论著 • 上一篇    下一篇

度普利尤单抗治疗123例特应性皮炎的疗效及安全性分析

黄馨1    陈筱昀1    李亚萍1    梁兴堃2    张桂英1    周英1    湛意1    罗帅寒天1    廖洁月   肖嵘1    龙海1
  

  1. 1中南大学湘雅二医院皮肤科  中南大学皮肤性病研究所  湖南省皮肤重大疾病与皮肤健康临床医学研究中心,长沙  410011;2北京大学信息管理系,北京  100871
    黄馨和陈筱昀对本文有同等贡献

  • 收稿日期:2022-01-10 修回日期:2022-04-15 发布日期:2022-06-02
  • 通讯作者: 龙海 E-mail:dr.hailong@csu.edu.cn
  • 基金资助:
    国家自然科学基金(82003364);长沙市杰出创新青年培养计划项目(kq2009033);长沙市自然科学基金(kq2014250)

Efficacy and safety of dupilumab in the treatment of 123 cases of atopic dermatitis

Huang Xin1, Chen Xiaoyun1, Li Yaping1, Liang Xingkun2, Zhang Guiying1, Zhou Ying1, Zhan Yi1, Luo Shuaihantian1, Liao Jieyue1, Xiao Rong1, Long Hai1   

  1. 1Department of Dermatology, The Second Xiangya Hospital of Central South University, Institute of Dermatology and Venereology of Central South University, Hunan Clinical Medicine Research Center for Major Skin Diseases and Skin Health, Changsha 410011, China; 2Department of Information Management, Peking University, Beijing 100871, China
    Huang Xin  and Chen Xiaoyun contributed equally to the article
  • Received:2022-01-10 Revised:2022-04-15 Published:2022-06-02
  • Contact: Long Hai E-mail:dr.hailong@csu.edu.cn
  • Supported by:
    National Natural Science Foundation of China (82003364); Innovation Young Talents Program of Changsha Science and Technology Bureau (kq2009033); Changsha Municipal Natural Science Foundation (kq2014250)

摘要: 【摘要】 目的 探讨度普利尤单抗治疗特应性皮炎(AD)的临床疗效及安全性。方法 通过双向性研究分析2020年7月至2022年3月于中南大学湘雅二医院皮肤科接受度普利尤单抗治疗的123例AD患者的临床资料,评估度普利尤单抗的疗效及安全性。主要指标为治疗前、治疗4、8、12、16周的患者湿疹面积和严重程度指数(EASI)、瘙痒峰值数字评定量表(NRS)、以患者为导向的湿疹测量评分(POEM)和皮肤病生活质量指数(DLQI)评分,同时记录不良反应及不良事件。治疗前后各评分的比较采用配对样本t检验或重复测量资料的方差分析;不同类型皮损及不同IgE水平患者疗效比较采用Mann-Whitney U检验;采用基于稳健标准误的多元回归模型分析疗效的影响因素。结果 123例AD患者中,107例纳入疗效分析,85例(79.44%)完成了至少4周治疗,其中6例(7.06%)达EASI75,23例(27.06%)达EASI50,EASI、NRS、POEM、DLQI评分(10.41 ± 6.72、4.12 ± 1.74、8.60 ± 4.29、7.81 ± 4.38)均显著低于治疗前(18.08 ± 10.69、7.21 ± 2.01、16.88 ± 5.74、12.95 ± 5.95),均P < 0.001。共47例(43.93%)完成了至少16周治疗,28例成人患者中23例(82.14%)、19例青少年及儿童中17例(89.47%)达EASI75及以上;治疗4、8、12、16周EASI、NRS、POEM、DLQI评分与治疗前相比差异均有统计学意义(均P < 0.001),且第4、8、12、16周各评分均显著低于前一相邻时间点(均P < 0.05)。治疗4周时,伴结节性痒疹的AD患者EASI评分改善率显著低于不伴者(U = 151.00,P = 0.006),而伴与不伴干皮症的AD患者间EASI评分改善率差异无统计学意义(P > 0.05);治疗16周时,不同类型皮损患者间EASI评分改善率差异无统计学意义(均P > 0.05)。基于稳健标准误的多元回归分析显示,第16周时EASI改善程度与皮疹类型无关(β = 3.20,P = 0.075),和年龄(β = -0.22,P = 0.030)、成年与否(β = 9.54,P = 0.049)、直系亲属家族史(β = 7.46,P = 0.017)具有相关性;NRS评分改善程度与皮疹类型(β = 0.55,P = 0.032)、年龄(β = -0.04,P = 0.033)、体重(β = -0.05,P = 0.020)、成年与否(β = 2.06,P = 0.003)、是否合并使用抗组胺药物(β = -1.91,P = 0.001) 具有相关性。不良反应:123例患者中,6例(4.88%)发生结膜炎,2例(1.63%)出现面部红斑。不良事件:1例右前额出现白癜风样改变,3例分别因过敏性紫癜、双上肢周围神经远端轴索损害、癫痫停药,与度普利尤单抗的相关性不确定。结论 度普利尤单抗治疗AD疗效显著,总体安全性好,可作为传统治疗欠满意患者的治疗新选择。

关键词: 皮炎, 特应性, 生物制剂, 治疗结果, 药物毒性, 度普利尤单抗

Abstract: 【Abstract】 Objective To investigate clinical efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD). Methods An ambispective study was conducted on 123 AD patients treated with dupilumab in Department of Dermatology, the Second Xiangya Hospital of Central South University from July 2020 to March 2022, clinical data were collected, and efficacy and safety of dupilumab were evaluated. Primary outcomes included scores of eczema area and severity index (EASI), patient-oriented eczema measure(POEM), peak pruritus numerical rating scale (NRS) and dermatology life quality index (DLQI) before and after 4-, 8-, 12- and 16-week treatment, and adverse reactions and events were recorded. Comparison of scores before and after treatment was performed using paired t test or repeated measures analysis of variance, Mann-Whitney U test was used for the comparison of efficacy among patients with different types of skin lesions or different IgE levels, and multiple regression model based on robust standard errors was used to analyze factors influencing the efficacy. Results Among the 123 AD patients, 107 were enolled into the efficacy analysis, and 85 (79.44%) completed at least 4 weeks of treatment, including 6 (7.06%) achieving EASI75 and 23 (27.06%) achieving EASI50, and the EASI, NRS, POEM, DLQI scores (10.41 ± 6.72, 4.12 ± 1.74, 8.60 ± 4.29, 7.81 ± 4.38, respectively) significantly decreased compared with those before treatment (18.08 ± 10.69, 7.21 ± 2.01, 16.88 ± 5.74, 12.95 ± 5.95, respectively; all P < 0.001) in the 85 patients. Among the 107 patients, 47 (43.93%) completed at least 16 weeks of treatment. Among the 47 patients, 23 (82.14%) of 28 adults and 17 (89.47%) of 19 adolescents and children achieved 75% or greater improvement in EASI score; the EASI, NRS, POEM and DLQI scores before the treatment all significantly differred from those 4, 8, 12, 16 weeks after the treatment (all P < 0.001), and all the scores were significantly lower at weeks 4, 8, 12 and 16 than at the previous adjacent time points (all P < 0.05). At week 4 during the treatment, the EASI improvement rate was significantly lower in the AD patients with prurigo nodularis than in those without (U = 151.00, P = 0.006), while there was no significant difference in the EASI improvement rate between the AD patients with xeroderma and those without (P > 0.05); at week 16 during the treatment, there was no significant difference in the EASI improvement rate between patients with prurigo nodularis or xeroderma and those without(both P > 0.05). Multiple regression analysis based on robust standard errors at week 16 showed that the improvement degree in the EASI score was not correlated with the type of skin lesions (β = 3.20, P = 0.075), but correlated with age (β = -0.22, P = 0.030), whether patients were in adulthood (β = 9.54, P = 0.049), immediate family history (β = 7.46, P = 0.017); the improvement degree in the NRS score was correlated with the type of skin lesions? (β = 0.55, P = 0.032), age (β = -0.04, P = 0.033), weight (β = -0.05, P = 0.020), whether patients were in adulthood (β = 2.06, P = 0.003) and whether patients received combined treatment with antihistamines (β = -1.91, P = 0.001). Adverse reactions: among the 123 patients, 6 (4.88%) developed conjunctivitis, and 2 (1.63%) developed facial erythema. Adverse events: vitiligo-like changes occurred on the right forehead of 1 patient, and 3 patients discontinued the treatment with dupilumab due to Henoch-Sch?nlein purpura, distal axonal damage in peripheral nerves in both upper limbs, and epilepsy, respectively. The causal relationship between these adverse events and dupilumab was unclear. Conclusion Dupilumab is effective in the treatment of AD with high overall safety, and can serve as a new treatment option for AD patients with an unsatisfactory response to traditional treatment.

Key words: Dermatitis, atopic, Biological agents, Treatment outcome, Drug toxicity, Dupilumab