双螨皮下免疫治疗时序疗法的3年疗效与安全性评估

doi:10.3969/j.issn.1006-5725.2025.21.016

Abstract

Abstract:

Objective To investigate the effects of different administration times on the efficacy and safety of subcutaneous immunotherapy using dual mite extracts in patients with allergic rhinitis （AR）. Methods This study was designed as a retrospective cohort analysis. Thirty-nine mite-sensitized AR patients who completed three years of standardized dual-mite subcutaneous immunotherapy （SCIT） were included. Based on self-selected and consistently maintained injection schedules， patients were non-randomly assigned to either a morning dosing group （MD group， 8：00—12：00， n = 19） or an afternoon dosing group （AD group， 14：00—18：00， n = 20）， with further subgroup stratification conducted at 2-hour intervals. Nasal and ocular symptoms were evaluated before and after treatment using the visual analog scale （VAS）， and all adverse reactions were systematically recorded. Results The AD group exhibited significantly greater improvement in nasal itching compared to the MD group （median difference： -2 vs. 0， U = 118.5， P = 0.04， effect size r = 0.33）. The AD group also demonstrated favorable trends toward improved sneezing， nasal congestion， rhinorrhea， and total VAS score， although these differences did not reach statistical significance. In the subgroup analysis by 2-hour intervals， the 16：00—18：00 subgroup showed greater symptom relief than the 8：00—10：00 subgroup， though the difference was not statistically significant. No significant differences were observed between the two groups in the incidence of total， local， or systemic adverse reactions （P > 0.05）， and no moderate or severe systemic adverse events occurred. Conclusions This preliminary retrospective analysis indicates that afternoon administration of dual-mite SCIT， particularly between 16：00 and 18：00， may enhance the improvement of nasal symptoms without elevating safety concerns. The timing of SCIT administration could therefore represent a promising avenue for treatment optimization.

Key words: subcutaneous immunotherapy, chronotherapy, allergic rhinitis, efficacy, side effect

CLC Number:

R730.51

Hang LI,Xiaomei YANG,Wen LYU,Huimin CHEN,Rui. XU. Three⁃year evaluation of the efficacy and safety of chronotherapy in dual⁃allergen subcutaneous immunotherapy[J]. The Journal of Practical Medicine, 2025, 41(21): 3405-3411.

Figures/Tables 4

Tab.1

Fig.1

Fig. 2

Fig.3

References 31

[1]	BOUSQUET J， ANTO J M， BACHERT C， et al. Allergic rhinitis［J］. Nat Rev Dis Primers， 2020， 6（1）： 95. doi:10.1038/s41572-020-00227-0 doi: 10.1038/s41572-020-00227-0
[2]	胡泽功，白燕. 过敏原特异性免疫治疗的研究进展［J］. 实用医学杂志，2025，41（11）：1760-1766.
[3]	PENAGOS M， DURHAM S R. Duration of allergen immunotherapy for inhalant allergy［J］. Curr Opin Allergy Clin Immunol， 2019， 19（6）： 594. doi:10.1097/aci.0000000000000585 doi: 10.1097/aci.0000000000000585
[4]	CHU D K， WOOD R A， FRENCH S， et al. Oral immunotherapy for peanut allergy （PACE）： A systematic review and meta-analysis of efficacy and safety［J］. Lancet， 2019， 393（10187）： 2222-2232. doi:10.1016/s0140-6736(19)30420-9 doi: 10.1016/s0140-6736(19)30420-9
[5]	NELSON H S， SOWERS T， PLUNKETT G， et al. The Art of Dosing for Subcutaneous Immunotherapy in North America［J］. J Allergy Clin Immunol Pract， 2024， 12（1）： 13-22. doi:10.1016/j.jaip.2023.06.036 doi: 10.1016/j.jaip.2023.06.036
[6]	SOHN M H. Efficacy and Safety of Subcutaneous Allergen Immunotherapy for Allergic Rhinitis［J］. Allergy Asthma Immunol Res， 2018， 10（1）： 1-3. doi:10.4168/aair.2018.10.1.1 doi: 10.4168/aair.2018.10.1.1
[7]	CONTOLI M， PORSBJERG C， BUCHS S， et al. Real-world， long-term effectiveness of allergy immunotherapy in allergic rhinitis： Subgroup analyses of the REACT study［J］. J Allergy Clin Immunol， 2023， 152（2）： 445-452.e4. doi:10.1016/j.jaci.2023.02.024 doi: 10.1016/j.jaci.2023.02.024
[8]	BINDER E， HOLOPAINEN E， MALMBERG H， et al. Anamnestic data in allergic rhinitis［J］. Allergy， 1982， 37（6）： 389-396. doi:10.1111/j.1398-9995.1982.tb02317.x doi: 10.1111/j.1398-9995.1982.tb02317.x
[9]	SMOLENSKY M H， REINBERG A， LABRECQUE G. Twenty-four hour pattern in symptom intensity of viral and allergic rhinitis： Treatment implications［J］. J Allergy Clin Immunol， 1995， 95（5）： 1084-1096. doi:10.1016/s0091-6749(95)70212-1 doi: 10.1016/s0091-6749(95)70212-1
[10]	REINBERG A， GERVAIS P， LEVI F， et al. Circadian and circannual rhythms of allergic rhinitis： An epidemiologic study involving chronobiologic methods［J］. J Allergy Clin Immunol， 1988， 81（1）： 51-62. doi:10.1016/0091-6749(88)90220-5 doi: 10.1016/0091-6749(88)90220-5
[11]	NAHMIAS Y， ANDROULAKIS I P. Circadian Effects of Drug Responses［J］. Annu Rev Biomed Eng， 2021， 23： 203-224. doi:10.1146/annurev-bioeng-082120-034725 doi: 10.1146/annurev-bioeng-082120-034725
[12]	TUREK F W. Circadian clocks： Not your grandfather′s clock［J］. Science， 2016， 354（6315）： 992-993. doi:10.1126/science.aal2613 doi: 10.1126/science.aal2613
[13]	DRUZD D， MATVEEVA O， INCE L， et al. Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses［J］. Immunity， 2017， 46（1）： 120-132. doi:10.1016/j.immuni.2016.12.011 doi: 10.1016/j.immuni.2016.12.011
[14]	BALLESTA A， INNOMINATO P F， DALLMANN R， et al. Systems Chronotherapeutics［J］. Pharmacol Rev， 2017， 69（2）： 161-199. doi:10.1124/pr.116.013441 doi: 10.1124/pr.116.013441
[15]	STORMS W W. Pharmacologic approaches to daytime and nighttime symptoms of allergic rhinitis［J］. J Allergy Clin Immunol， 2004， 114（5）： S146-S153. doi:10.1016/j.jaci.2004.08.045 doi: 10.1016/j.jaci.2004.08.045
[16]	SMOLENSKY M H， LEMMER B， REINBERG A E. Chronobiology and chronotherapy of allergic rhinitis and bronchial asthma［J］. Adv Drug Deliv Rev， 2007， 59（9-10）： 852-882. doi:10.1016/j.addr.2007.08.016 doi: 10.1016/j.addr.2007.08.016
[17]	IGARASHI S， SUZUKI K， NAKAMURA Y， et al. The Efficacy of Sublingual Immunotherapy for Allergic Rhinitis May Vary with the Time of Day［J］. Int Arch Allergy Immunol， 2016， 171（2）： 111-118. doi:10.1159/000450954 doi: 10.1159/000450954
[18]	LIAO F， CHEN S， WANG L， et al. Morning Versus Evening Dosing of Sublingual Immunotherapy in Allergic Asthma： A Prospective Study［J］. Front Pediatr， 2022， 10： 892572. doi:10.3389/fped.2022.892572 doi: 10.3389/fped.2022.892572
[19]	LI H， YANG X， WEN Y， et al. Three‐Year Longitudinal Evaluation of Timing Effects on Subcutaneous Immunotherapy Efficacy and Safety in Allergic Rhinitis［J］. Clin Exp Allergy， 2025： cea.70075. doi:10.1111/cea.70075 doi: 10.1111/cea.70075
[20]	LÓPEZ-SANZ C， JIMÉNEZ-SAIZ R， ESTEBAN V， et al. Mast Cell Desensitization in Allergen Immunotherapy［J］. Front Allergy， 2022， 3： 898494. doi:10.3389/falgy.2022.898494 doi: 10.3389/falgy.2022.898494
[21]	COX L， LARENAS-LINNEMANN D， LOCKEY R F， et al. Speaking the same language： The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System［J］. J Allergy Clin Immunol， 2010， 125（3）： 569-574.e7. doi:10.1016/j.jaci.2009.10.060 doi: 10.1016/j.jaci.2009.10.060
[22]	FREW A J. Allergen immunotherapy［J］. J Allergy Clin Immunol， 2010， 125（2）： S306-S313. doi:10.1016/j.jaci.2009.10.064 doi: 10.1016/j.jaci.2009.10.064
[23]	WANG L， WANG C， LOU H， et al. Antihistamine premedication improves safety and efficacy of allergen immunotherapy［J/OL］. Ann Allergy Asthma Immunol， 2021， 127（3）： 363-371.e1. doi:10.1016/j.anai.2021.05.023 doi: 10.1016/j.anai.2021.05.023
[24]	HERMIDA R C， AYALA D E， SMOLENSKY M H， et al. Chronotherapy improves blood pressure control and reduces vascular risk in CKD［J］. Nat Rev Nephrol， 2013， 9（6）： 358-368. doi:10.1038/nrneph.2013.79 doi: 10.1038/nrneph.2013.79
[25]	SHAMJI M H， LJØRRING C， FRANCIS J N， et al. Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy.［J］. Allergy， 2012， 67（2）： 217-226. doi:10.1111/j.1398-9995.2011.02745.x doi: 10.1111/j.1398-9995.2011.02745.x
[26]	NAKAO A. Circadian Regulation of the Biology of Allergic Disease： Clock Disruption Can Promote Allergy［J］. Front Immunol， 2020， 11： 1237. doi:10.3389/fimmu.2020.01237 doi: 10.3389/fimmu.2020.01237
[27]	LIN Y， HE L， CAI Y， et al. The role of circadian clock in regulating cell functions： Implications for diseases［J］. MedComm （2020）， 2024， 5（3）： e504. doi:10.1002/mco2.504 doi: 10.1002/mco2.504
[28]	FIDAN V， ALP H H， GOZELER M， et al. Variance of melatonin and cortisol rhythm in patients with allergic rhinitis［J］. Am J Otolaryngol， 2013， 34（5）： 416-419. doi:10.1016/j.amjoto.2013.03.004 doi: 10.1016/j.amjoto.2013.03.004
[29]	ANDO N， NAKAMURA Y， ISHIMARU K， et al. Allergen-specific basophil reactivity exhibits daily variations in seasonal allergic rhinitis［J］. Allergy， 2015， 70（3）： 319-322. doi:10.1111/all.12552 doi: 10.1111/all.12552
[30]	LONG J E， DRAYSON M T， TAYLOR A E， et al. Morning vaccination enhances antibody response over afternoon vaccination： A cluster-randomised trial［J］. Vaccine， 2016， 34（24）： 2679-2685. doi:10.1016/j.vaccine.2016.04.032 doi: 10.1016/j.vaccine.2016.04.032
[31]	ZHANG H， LIU Y， LIU D， et al. Time of day influences immune response to an inactivated vaccine against SARS-CoV-2［J］. Cell Res， 2021， 31（11）： 1215-1217. doi:10.1038/s41422-021-00541-6 doi: 10.1038/s41422-021-00541-6

特征	上午组（n = 19）	下午组（n = 20）	t/χ2值	P值
人口学特征
年龄/岁	30.53 ± 11.61	24.40 ± 9.66	1.789	0.081
性别/［例（%）］			0.058	0.810
男	14（73.7）	13（65.0）
女	5（26.3）	7（35.0）
身高/cm	158.21 ± 20.18	153.65 ± 19.06	0.726	0.472
体质量/kg	51.84 ± 19.83	47.08 ± 15.37	0.840	0.405
治疗前症状评分［M（P₂₅，P₇₅）］
打喷嚏	3.00（0.00， 6.00）	4.75（2.12， 8.00）	1.402	0.161
鼻塞	3.00（0.00， 4.75）	5.00（0.00， 8.00）	0.874	0.382
鼻痒	2.00（0.00， 4.00）	2.50（1.00， 5.50）	1.549	0.121
流涕	3.00（0.00， 5.50）	4.50（1.00， 7.25）	1.110	0.267
眼痒	1.00（0.00， 3.25）	1.00（0.00， 5.25）	0.340	0.734
流泪	0.00（0.00， 1.75）	0.00（0.00， 2.00）	0.401	0.688
总分	14.50（4.00， 22.25）	19.50（8.50， 34.50）	1.293	0.196

Three⁃year evaluation of the efficacy and safety of chronotherapy in dual⁃allergen subcutaneous immunotherapy

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 4

References 31

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Hanqi YANG,Lingna. HE. The therapeutic effect of acupuncture combined with moxibustion on insomnia related to cerebral infarction based on the "Yuan⁃Luo Point Pairing" and its impact on serum Hcrt⁃1， 5⁃HT， and slow wave EEG [J]. The Journal of Practical Medicine, 2025, 41(8): 1253-1258.
[2]	Youqiang ZHANG,Ling YAN,Wei LIAO,Guang WANG,Xiaoheng CHEN,Rui FAN,Zuwei. LIU. Study of modified anteromedial approach and preserves the superior extensor retinaculum for clinical effect of Pilon fracture [J]. The Journal of Practical Medicine, 2025, 41(3): 358-364.
[3]	Jiahao CHEN,Yong HUANG,Ruibing FENG,Xiaofeng DUAN,Gang WU,Yizheng HUANG,Haitao ZHANG,Chao LI,Yinshuai DING,Hao. HU. Treatment effect and safety analysis of intraspinal tumor under 3D microscope [J]. The Journal of Practical Medicine, 2025, 41(3): 371-378.
[4]	Muying HUANG,Chu LIU,Jiaman LIU,Zhicong. WANG. Early identification of high⁃risk children who develop systemic adverse reactions related to dust mite allergy subcutaneous immunotherapy [J]. The Journal of Practical Medicine, 2025, 41(19): 3065-3071.
[5]	Yuchen ZHAO,Manting XU,Jing BAO,Liang XIA. Clinical evaluation of daratumumab in combination with lenalidomide and bortezomib and with daratumumab， bortezomib， and dexamethasone for the treatment of relapsed and refractory multiple myeloma [J]. The Journal of Practical Medicine, 2025, 41(18): 2913-2919.
[6]	Hecheng SUN,Haiyang WANG. Radiofrequency ablation for lower extremity varicose veins： A comprehensive review [J]. The Journal of Practical Medicine, 2025, 41(17): 2761-2766.
[7]	Daojun BAO,Gomei ZHU,Gehong PENG. New directions in treatment for lower extremity varicose veins： Advances in ultrasound⁃guided microwave ablation applications [J]. The Journal of Practical Medicine, 2025, 41(15): 2435-2440.
[8]	Yuling DUAN,Xuezhi ZHOU,Yongyi LI,Lixia MA,Desheng YANG,Jiao CHENG,Yan WU,Tao LIU,Guoyuan JIANG,Mei. WANG. Clinical value analysis of different MRI measurement methods in evaluating the efficacy of neoadjuvant therapy for breast cancer [J]. The Journal of Practical Medicine, 2025, 41(14): 2152-2159.
[9]	Rouzi REBOTE,Hanshuo ZHANG,Guangnan YANG,Jie BAI,Qiang JIANG,Zhengcao LU,Wen LI,Yu DING. Clinical observation of Endo⁃LOVE combined with NR⁃PRF in the treatment of LDD：Focusing on the improvement of postoperative residual symptoms [J]. The Journal of Practical Medicine, 2025, 41(12): 1800-1807.
[10]	Linyu ZENG,Ziming CHEN,Junqing ZENG,Yi YAN,Daying ZHANG,Lili GU. Ultrasound measurement of sciatic nerve cross⁃sectional area in early outcome assessment after endoscopic surgery for unilateral lumbar disc herniation [J]. The Journal of Practical Medicine, 2025, 41(1): 35-40.
[11]	Xi LIU,Xiaona LIU,Chao LI,Rui XIAN,Lihong CUI. Efficacy analysis of different regimens for treatment of Helicobacter pylori infection combined with small intestinal bacterial overgrowth [J]. The Journal of Practical Medicine, 2024, 40(9): 1303-1308.
[12]	Yuan LIU,Jing LAI,Danying MA,Lingzi WU,Wei. WANG. Analysis of fatigue status and influencing factors of adult patients at home after cardiac surgery [J]. The Journal of Practical Medicine, 2024, 40(24): 3547-3553.
[13]	Yingyuan ZHANG,Chunyan MOU,Danqing XU,Yuanzhen WANG,Lixian CHANG,Chunyun LIU,Weikun LI,Hongyan WEI,Li LIU. Comparison of clinical efficacy of TMF and TDF in the treatment of hepatitis B liver fibrosis [J]. The Journal of Practical Medicine, 2024, 40(22): 3215-3220.
[14]	Fangmin GENG,Yuandan HE,Wenjuan LI,Qianqian LIU,Hongwei ZHANG,Zhangping LU,Lianhua WEI. Values of different DIC scoring systems in early diagnosis and prognosis prediction of coagulation dysfunction in sepsis patients [J]. The Journal of Practical Medicine, 2024, 40(2): 248-252.
[15]	Yanping WANG,Wenhui GAO,Yanting WU,Jun YANG,Yi ZHOU,Xiaoshun. JIAN. Analysis of influencing factors on clinical efficacy of neutropenia with febrile neutropenia in tumor patients [J]. The Journal of Practical Medicine, 2024, 40(18): 2597-2601.