度普利尤单抗治疗老年特应性皮炎的疗效观察

doi:10.19723/j.issn.1671-167X.2025.02.012

摘要/Abstract

摘要：

目的: 观察度普利尤单抗治疗老年特应性皮炎(atopic dermatitis, AD)的疗效及安全性。方法: 回顾性收集北京安贞医院皮肤性病科2021年1月至2023年10月收治的接受度普利尤单抗治疗至少16周的老年AD患者, 比较治疗前、治疗期间以及治疗后的临床指标, 包括瘙痒数字评价量表(pruritus numerical rating score, PNRS)、湿疹面积和严重程度指数(eczema area and severity index, EASI)、皮肤病生活质量指数(dermatology life quality index, DLQI), 同时记录发生的不良反应; 比较治疗前及治疗16周后外周血干扰素γ (interferon-γ, IFN-γ)、白细胞介素(interleukin, IL)-4、IL-6表达情况。结果: 共90例老年性特应性皮炎患者纳入本研究, EASI、PNRS、DLQI评分在治疗期间均呈下降趋势, 具体表现为在启动治疗后的前4周内快速下降, 随后下降逐渐趋于平缓。两两时间点比较结果表明, 治疗后第4周EASI、PNRS和DLQI评分均较治疗前明显降低(P＜0.001); 治疗后第16周时, 以上疗效指标评分均进一步降低, 与第4周相比差异有统计学意义(P＜0.01), 其中EASI评分在各个时间点均比前一时间点明显降低, 表明患者皮损持续明显改善。对度普利尤单抗的总体疗效进行评价, 治疗4周时有62.89%的患者达到EASI-50(即EASI评分下降≥50%), 74.4%的患者DLQI评分下降≥4分; 16周时有57.8%的患者达到EASI-75, 32.2%的患者达到EASI-90, 且所有患者的PNRS、DLQI评分均下降≥4分。外周血炎症指标表达水平检测结果表明, 治疗16周后IL-4、IL-6表达水平分别为(31.62±6.23) ng/L、(14.36±2.25) ng/L, 均较治疗前明显降低(P＜0.001), 而IFN-γ的表达水平为(15.37±3.14) ng/L, 较治疗前上升(P＜0.001)。不良反应主要为结膜炎(2例)、注射部位反应(3例)及背部多发性细菌性毛囊炎(2例), 对症治疗均可缓解, 未出现严重不良反应。结论: 度普利尤单抗在老年AD治疗中表现出良好的疗效, 可有效改善瘙痒、皮损等临床症状, 并能提高患者生活质量, 治疗期间未出现严重的不良反应, 安全性较好, 值得临床推广。

关键词: 度普利尤单抗, 老年, 特应性皮炎, 炎性反应

Abstract:

Objective: To evaluate the efficacy and safety of dupilumab in the treatment of atopic dermatitis in the elderly. Methods: In this study, elderly patients with atopic dermatitis treated with dupilumab for at least 16 weeks in the Department of Dermatology and Venereology of Beijing Anzhen Hospital from January 2021 to October 2023 were retrospectively collected. Clinical indicators were compared before, during and after treatment, including pruritus numerical rating score (PNRS), eczema area and severity index (EASI), dermatology life quality index (DLQI) score, and the incidence of adverse events was recorded. The expression of interferon γ (IFN-γ), interleukin-4 (IL-4) and interleukin-6 (IL-6) in peripheral blood were compared before treatment and after 16 weeks of treatment. Results: A total of 90 elder patients with atopic dermatitis were included, EASI, PNRS and DLQI scores all showed a gradual downward trend during the treatment period, which was manifested as a rapid decline in the first 4 weeks after starting treatment, and then the decline gradually leveled off. The results of point-to-point comparison showed that EASI, PNRS and DLQI scores in 4 weeks after treatment were significantly lower than those before treatment (P < 0.001); In the 16th week after treatment, the scores of the above therapeutic indicators were further reduced, and the difference was statistically significant compared with the 4th week (P < 0.01); The EASI score was significantly lower at each time point than the previous time point, indicating that the patients' skin lesions continued to improve significantly. The overall efficacy of dupliumab was evaluated. After 4 weeks of treatment, 62.89% of patients achieved EASI-50 (EASI score decreased by ≥50%), and 74.4% of patients' DLQI score decreased by ≥4 points. After 16 weeks of treatment, 57.8% of the patients achieved EASI-75, 32.2% achieved EASI-90, and the PNRS and DLQI scores of all the patients decreased by ≥4 points. After 16 weeks of treatment, the expression levels of IL-4 and IL-6 were (31.62±6.23) ng/L and (14.36±2.25) ng/L, respectively, which were significantly lower than those before treatment (P < 0.001), and the expression level of IFN-γ was (15.37±3.14) ng/L, which was higher than before treatment (P < 0.001).The main adverse reactions were conjunctivitis (2 cases), injection site reaction (3 cases) and multiple bacterial folliculitis of the back (2 cases), which could be alleviated by symptomatic treatment, and no serious adverse reactions occurred. Conclusion: Dupilumab has shown good efficacy in the treatment of elderly atopic dermatitis, which can effectively improve clinical symptoms such as itching and skin lesions, improve the quality of life of patients, and no serious adverse reactions occurred during treatment, so it is safe and worthy of clinical promotion.

Key words: Dupilumab, Old age, Atopic dermatitis, Inflammatory response

中图分类号:

R758.2

孙冉, 吴宇皓, 狄梅, 王晓阳. 度普利尤单抗治疗老年特应性皮炎的疗效观察[J]. 北京大学学报（医学版）, 2025, 57(2): 298-302.

Ran SUN, Yuhao WU, Mei DI, Xiaoyang WANG. Observation of the efficacy of dupilumab for treatment of atopic dermatitis in the elderly[J]. Journal of Peking University (Health Sciences), 2025, 57(2): 298-302.

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参考文献 33

1	Teng Y , Zhong H , Yang X , et al. Current and emerging therapies for atopic dermatitis in the elderly[J]. Clin Interv Aging, 2023, 18 (1): 1641- 1652.
2	Schuler CF , Billi AC , Maverakis E , et al. Novel insights into atopic dermatitis[J]. J Allergy Clin Immunol, 2023, 151 (5): 1145- 1154. doi: 10.1016/j.jaci.2022.10.023
3	Kim J , Ahn K . Atopic dermatitis endotypes: Knowledge for personalized medicine[J]. Curr Opin Allergy Clin Immunol, 2022, 22 (3): 153- 159. doi: 10.1097/ACI.0000000000000820
4	Adam DN , Gooderham MJ , Beecker JR , et al. Expert consensus on the systemic treatment of atopic dermatitis in special populations[J]. J Eur Acad Dermatol Venereol, 2023, 37 (6): 1135- 1148. doi: 10.1111/jdv.18922
5	Reich K , Thyssen JP , Blauvelt A , et al. Efficacy and safety of abrocitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: A randomised, double-blind, multicentre phase 3 trial[J]. Lancet, 2022, 400 (10348): 273- 282. doi: 10.1016/S0140-6736(22)01199-0
6	Narla S , Silverberg JI , Simpson EL . Management of inadequate response and adverse effects to dupilumab in atopic dermatitis[J]. J Am Acad Dermatol, 2022, 86 (3): 628- 636. doi: 10.1016/j.jaad.2021.06.017
7	中华医学会皮肤性病学分会免疫学组, 特应性皮炎协作研究中心. 中国特应性皮炎诊疗指南(2020版)[J]. 中华皮肤科杂志, 2020, 53 (2): 81- 88.
8	Hanifin JM , Baghoomian W , Grinich E , et al. The eczema area and severity index: A practical guide[J]. Dermatitis, 2022, 33 (3): 187- 192. doi: 10.1097/DER.0000000000000895
9	Wikström L , Nilsson M , Broström A , et al. Patients' self-reported nausea: Validation of the numerical rating scale and of a daily summary of repeated numerical rating scale scores[J]. J Clin Nurs, 2019, 28 (5/6): 959- 968.
10	Finlay AY , Khan GK . Dermatology life quality index (DLQI): A simple practical measure for routine clinical use[J]. Clin Exp Dermatol, 1994, 19 (3): 210- 216. doi: 10.1111/j.1365-2230.1994.tb01167.x
11	Tavecchio S , Angileri L , Pozzo GF , et al. Efficacy of dupilumab on different phenotypes of atopic dermatitis: One-year experience of 221 patients[J]. J Clin Med, 2020, 9 (9): 2684. doi: 10.3390/jcm9092684
12	鞠延娇, 门月华, 谢志强. 度普利尤单抗治疗老年顽固性重度特应性皮炎30例临床观察[J]. 中国皮肤性病学杂志, 2022, 36 (9): 1026- 1031.
13	Goh MS , Yun JS , Su JC . Management of atopic dermatitis: A narrative review[J]. Med J Aust, 2022, 216 (11): 587- 593. doi: 10.5694/mja2.51560
14	Wang S , Zhu R , Gu C , et al. Distinct clinical features and serum cytokine pattern of elderly atopic dermatitis in China[J]. J Eur Acad Dermatol Venereol, 2020, 34 (10): 2346- 2352. doi: 10.1111/jdv.16346
15	Zhou L , Leonard A , Pavel AB , et al. Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis[J]. J Allerge Clin Imm, 2019, 144 (1): 144- 156. doi: 10.1016/j.jaci.2019.01.015
16	Paller AS , Simpson EL , Siegfried EC , et al. Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: A randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet, 2022, 400 (10356): 908- 919. doi: 10.1016/S0140-6736(22)01539-2
17	Zhao Y , Wu L , Lu Q , et al. The efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis: A randomized, double-blind, placebo-controlled study[J]. Br J Dermatol, 2022, 186 (4): 633- 641. doi: 10.1111/bjd.20690
18	Faiz S , Giovannelli J , Podevin C , et al. Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort[J]. J Am Acad Dermatol, 2019, 81 (1): 143- 151. doi: 10.1016/j.jaad.2019.02.053
19	Lasek A , Bellon N , Mallet S , et al. Effectiveness and safety of dupilumab in the treatment of atopic dermatitis in children (6-11 years): Data from a French multicentre retrospective cohort in daily practice[J]. J Eur Acad Dermatol Venereol, 2022, 36 (12): 2423- 2429. doi: 10.1111/jdv.18450
20	Jang DH , Heo SJ , Jung HJ , et al. Retrospective study of dupilumab treatment for moderate to severe atopic dermatitis in Korea: Efficacy and safety of dupilumab in real-world practice[J]. J Clin Med, 2020, 9 (6): 1982. doi: 10.3390/jcm9061982
21	Ariёns L , van der Schaft J , Bakker DS , et al. Dupilumab is very effective in a large cohort of difficult-to-treat adult atopic dermatitis patients: First clinical and biomarker results from the BioDay registry[J]. Allergy, 2020, 75 (1): 116- 126. doi: 10.1111/all.14080
22	刘擘, 宋晓婷, 李若瑜, 等. 度普利尤单抗治疗特应性皮炎的疗效及安全性分析[J]. 中华皮肤科杂志, 2022, 55 (4): 295- 298.
23	Blauvelt A , Guttman-Yassky E , Paller AS , et al. Long-term efficacy and safety of dupilumab in adolescents with moderate-to-severe atopic dermatitis: Results through week 52 from a phase Ⅲ open-label extension trial (LIBERTY AD PED-OLE)[J]. Am J Clin Dermatol, 2022, 23 (3): 365- 383. doi: 10.1007/s40257-022-00683-2
24	王上上, 潘晓玉, 李亚楠, 等. 中重度老年特应性皮炎新型系统治疗有效性及安全性的荟萃分析[J]. 中华医学杂志, 2023, 103 (32): 2509- 2515.
25	Vittrup I , Krogh NS , Larsen H , et al. A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: Ineffectiveness in head-and-neck dermatitis[J]. J Eur Acad Dermatol Venereol, 2023, 37 (5): 1046- 1055. doi: 10.1111/jdv.18849
26	Patruno C , Fabbrocini G , Longo G , et al. Effectiveness and safety of long-term dupilumab treatment in elderly patients with atopic dermatitis: A multicenter real-life observational study[J]. Am J Clin Dermatol, 2021, 22 (4): 581- 586. doi: 10.1007/s40257-021-00597-5
27	Napolitano M , Fabbrocini G , Scalvenzi M , et al. Efficacy and safety of dupilumab in atopic dermatitis in elderly patients: A retrospective study[J]. Clin Exp Dermatol, 2020, 45 (7): 888- 890. doi: 10.1111/ced.14260
28	Gu C , Wu Y , Luo Y , et al. Real-world efficacy and safety of dupilumab in Chinese patients with atopic dermatitis: A single-centre, prospective, open-label study[J]. J Eur Acad Dermatol Venereol, 2022, 36 (7): 1064- 1073. doi: 10.1111/jdv.18109
29	He H , Olesen CM , Pavel AB , et al. Tape-strip proteomic profiling of atopic dermatitis on dupilumab identifies minimally invasive biomarkers[J]. Front Immunol, 2020, 11, 1768. doi: 10.3389/fimmu.2020.01768
30	孔羽薇. 特应性皮炎相关细胞因子的研究进展[J]. 临床儿科杂志, 2019, 37 (2): 148- 152.
31	石娴, 石年, 解崔林, 等. 特应性皮炎患者血清Vit D、tIgE、IL-4和IL-6水平检测及临床意义[J]. 检验医学与临床, 2017, 14 (24): 3605.
32	Busse PJ , Birmingham JM , Calatroni A , et al. Effect of aging on sputum inflammation and asthma control[J]. J Allergy Clin Immunol, 2017, 139 (6): 1808- 1818. doi: 10.1016/j.jaci.2016.09.015
33	李妍, 徐薇, 程海艳, 等. 白介素4、10、12、13、IFN-γ、TGF-β在不同时期特应性皮炎病人血清中的变化[J]. 首都医科大学学报, 2017, 10 (38): 635- 639.

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Scores	Before treatment	After treatment
Scores	Before treatment	4 weeks	8 weeks	16 weeks
EASI	29.5 (16.8, 35.3)	10.8 (7.5, 15.0)^*	7.3 (5.2, 15.4)^*#	5.0 (1.9, 7.5)^*#△
PNRS	8.6 (6.3, 10.0)	3.5 (1.5, 5.0)^*	2.6 (1.0, 4.4)^*	1.3 (0, 2.4)^*#
DLQI	15.0 (10.3, 20.4)	7.3 (4.8, 9.7)^*	6.6 (3.0, 8.9)^*	4.3 (2.4, 6.0)^*#

Inflammatory factors	Before treatment	16 weeks after treatment	t	P
IFN-γ/(ng/L)	9.75±1.78	15.37±3.14	7.290	＜0.001
IL-4/ (ng/L)	60.85±10.35	31.62±6.23	23.690	＜0.001
IL-6 /(ng/L)	22.57±3.53	14.36±2.25	47.356	＜0.001

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