英夫利昔单抗和乌司奴单抗致肺结核1例分析

doi:10.19803/j.1672-8629.20250104

摘要/Abstract

摘要： 目的探讨英夫利昔单抗和乌司奴单抗致肺结核不良反应及发生机制,为临床安全用药提供参考。方法分析1例克罗恩病患者使用英夫利昔单抗和乌司奴单抗致肺结核不良反应的病例,通过检索国内外相关文献进行讨论与总结。结果本例患者因克罗恩病,长期使用英夫利昔单抗治疗,后因产生肺结核而停用,经抗结核治疗后启用乌司奴单抗,治疗2个疗程后再次出现肺结核。加用异烟肼和利福平预防性抗结核治疗,同时重新启用乌司奴单抗,结果显示PPD试验转阴,患者肺结核症状未再发生。结论英夫利昔单抗和乌司奴单抗是目前克罗恩病常用的生物制剂,这类药物能够产生免疫抑制治疗作用,但也会导致感染性不良反应。临床在使用英夫利昔单抗和乌司奴单抗时需要密切关注肺结核不良反应,并给予预防性抗结核治疗。

关键词: 克罗恩病, 肺结核, 英夫利昔单抗, 乌司奴单抗, 药品不良反应

Abstract: Objective To investigate such adverse reactions as tuberculosis (TB) reactivation induced by infliximab and ustekinumab, and to explore the underlying mechanism. Methods One case of TB reactivation induced by infliximab and ustekinumab in a patient with Crohn’s disease was analyzed and related literature was reviewed. Results This patient with Crohn’s disease received long-term infliximab therapy. Treatment was discontinued due to the development of TB. After anti-TB treatment, ustekinumab was initiated. However, TB reoccurred after two courses of treatment. The patient then received prophylactic anti-tuberculosis therapy with isoniazid and rifampin concurrently with the re-initiation of ustekinumab. Results showed that the PPD test turned negative, and that TB symptoms occurred no more. Conclusion Infliximab and ustekinumab are commonly used biological agents for Crohn’s disease. While these drugs are immunosuppressive, they can cause infectious adverse reactions. Although ustekinumab is considered a relatively safe immunomodulator, it can still induce TB. Clinicians are advised to monitor patients for TB adverse reactions when infliximab or Ustekinumab is used. For patients who receive chronic ustekinumab therapy, prophylactic anti-TB treatment should be administered.

Key words: Crohn’s Disease, Tuberculosis, Infliximab, Ustekinumab, Adverse Drug Reaction

中图分类号:

周炜, 王利媛, 王芳, 孙艳艳, 夏一淼, 王法财. 英夫利昔单抗和乌司奴单抗致肺结核1例分析[J]. 中国药物警戒, 2026, 23(1): 105-108.

ZHOU Wei, WANG Liyuan, WANG Fang, SUN Yanyan, XIA Yimiao, WANG Facai. One Case of Tuberculosis Caused by Infliximab and Ustekinumab[J]. Chinese Journal of Pharmacovigilance, 2026, 23(1): 105-108.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://zgywjj.magtechjournal.com/CN/10.19803/j.1672-8629.20250104

https://zgywjj.magtechjournal.com/CN/Y2026/V23/I1/105

参考文献

[1] Inflammatory Bowel Disease Group of Chinese Society of Gastroenterology of Chinese Medical Association. Inflammatory Bowel Disease Quality Control Center of China. Chinese Clinical Practice Guideline on the Management of Crohn's Disease (2023, Guangzhou)[J]. Chin J Dig(中华消化杂志), 2024, 44(2): 100-132.
[2] ZHOU JL, BAO JC, LIAO XY, et al.Trends and Projections of Inflammatory Bowel Disease at the Global, Regional and National Levels, 1990-2050: a Bayesian Age-Period-Cohort Modeling Study[J]. BMC Public Health, 2023, 23(1): 2507.
[3] ZHANG Y, ZHENG WW, XU LQ, et al.The Incidence and Prevalence Change of Inflammatory Bowel Disease in Jinan from 2005 to 2022 Based on Jinan Medical Insurance Cohort[J]. Chin J Inflamm Bowel Dis(中华炎性肠病杂志), 2025, 9(2): 136-142.
[4] ADAMINA M, MINOZZI S, WARUSAVITARNE J, et al.ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment[J]. J Crohns Colitis, 2024, 18(10): 1556-1582.
[5] PONSIOEN CY, DE GROOF EJ, ESHUIS EJ, et al.Laparoscopic Ileocaecal Resection versus Infliximab for Terminal Ileitis in Crohn's Disease: a Randomised Controlled, Open-Label, Multicentre Trial[J]. Lancet Gastroenterol Hepatol, 2017, 2(11): 785-792.
[6] ZHANG W, ZHONG G, REN X, et al.Research Progress of Ustekinumab in the Treatment of Inflammatory Bowel Disease[J]. Front Immunol, 2024, 15: 1322054.
[7] WANG Z, LIAO W, CHEN Y, et al.Treatment with Antituberculosis Agents after Tuberculosis Activation during Ustekinumab Treatment: Safety and Effectiveness[J]. Arab J Gastroenterol, 2025, 26(1): 23-25.
[8] RENOUX MC, DUTRONC S, KOLLEN L, et al.A Case of Dissemin-ated Tuberculosis in a Child with Crohn's Disease after Treatment with Azathioprine, Adalimumab and Ustekinumab[J]. Arch Bron-coneumol, 2021, 57(8): 552-554.
[9] ERRICHETTI E, PICCIRILLO A.Latent Tuberculosis Reactivation in a Patient with Erythrodermic Psoriasis under Treatment with Ustekinumab and a Low Dose Steroid, Despite Isoniazid Chemopro-phylaxis[J]. Eur J Dermatol, 2014, 24(4): 508-509.
[10] S NCHEZ-MOYA AI, DAUDEN E. Peripheral Lymph Node Recurrence of Tuberculosis after Ustekinumab Treatment[J]. Arch Dermatol, 2012, 148(11): 1332-1333.
[11] TSAI TF, CHIU HY, SONG M, et al.A Case of Latent Tuberculosis Reactivation in a Patient Treated with Ustekinumab without Concomitant Isoniazid Chemoprophylaxis in the PEARL Trial[J]. Br J Dermatol, 2013, 168(2): 444-446.
[12] FALLAHI-SICHANI M, FLYNN JL, LINDERMAN JJ, et al.Differential Risk of Tuberculosis Reactivation among Anti-TNF Therapies is Due to Drug Binding Kinetics and Permeability[J]. J Immunol, 2012, 188(7): 3169-3178.
[13] GARDAM MA, KEYSTONE EC, MENZIES R, et al.Anti-Tumour Necrosis Factor Agents and Tuberculosis Risk: Mechanisms of Action and Clinical Management[J]. Lancet Infect Dis, 2003, 3(3): 148-155.
[14] CHOI MG, YE BD, YANG SK, et al.The Risk of Tuberculosis in Patients with Inflammatory Bowel Disease Treated with Vedolizumab or Ustekinumab in Korea[J]. J Korean Med Sci, 2022, 37(14): e107.
[15] ARBUÉS A, BREES D, CHIBOUT SD, et al. TNF-α Antagonists Differentially Induce TGF-β1-Dependent Resuscitation of Dormant-Like Mycobacterium Tuberculosis[J]. PLoS Pathog, 2020, 16(2): e1008312.
[16] LEBWOHL M, LEONARDI C, GRIFFITHS CE, et al.Long-Term Safety Experience of Ustekinumab in Patients with Moderate-to-Severe Psoriasis (Part I of II): Results from Analyses of General Safety Parameters from Pooled Phase 2 and 3 Clinical Trials[J]. J Am Acad Dermatol, 2012, 66(5): 731-741.
[17] VU A, GLASSMAN I, CAMPBELL G, et al.Host Cell Death and Modulation of Immune Response against Mycobacterium Tuberculosis Infection[J]. Int J Mol Sci, 2024, 25(11): 6255.
[18] NIELSEN MA, BENDIX M, HVAS CL, et al.Increased Mucosal and T-Cell Expression of 4-1BB and PD-1 are Modulated by Anti-TNFα Treatment in Crohns Disease[J]. Scand J Gastroenterol, 2025, 60(7): 698-706.
[19] WANG H, RUAN G, LI Y, et al.The Role and Potential Application of IL-12 in the Immune Regulation of Tuberculosis[J]. Int J Mol Sci, 2025, 26(7): 3106.
[20] CRUZ A, FRAGA AG, FOUNTAIN JJ, et al.Pathological Role of Interleukin 17 in Mice Subjected to Repeated BCG Vaccination after Infection with Mycobacterium Tuberculosis[J]. J Exp Med, 2010, 207(8): 1609-1616.
[21] HEIDARNEZHAD F, ASNAASHARI A, REZAEE SA, et al.Evaluation of Interleukin17 and Interleukin 23 Expression in Patients with Active and Latent Tuberculosis Infection[J]. Iran J Basic Med Sci, 2016, 19(8): 844-850.
[22] VERSTOCKT B, SALAS A, SANDS BE, et al.IL-12 and IL-23 Pathway Inhibition in Inflammatory Bowel Disease[J]. Nat Rev Gastroenterol Hepatol, 2023, 20(7): 433-446.
[23] CAI J, WEI J, NIE L, et al.Literature Analysis of Infliximab-Induced Tuberculosis[J]. Chin J Pharmacoepidemiol(药物流行病学杂志), 2018, 27(11): 765-768.
[24] CAI J, WEI J, JI LW.Literature Analysis of Tuberculosis Induced by Adalimumab[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2018, 15(11): 682-685.
[25] LIU R, LI Z, YE L, et al.Risk of Tuberculosis and Hepatitis B Reacti-vation in Patients with Crohn's Disease on Ustekinumab: a Nationwide Real-World Study[J]. Inflamm Bowel Dis, 2024, 30(1): 45-52.
[26] CHAN WSA, WONG Y, OON HHB, et al.Efficacy and Safety of Ustekinumab in the Treatment of Moderate to Severe Plaque Psoriasis in Singapore[J]. Singapore Med J, 2023, 64(7): 434-438.
[27] CHAVEZ-SANCHEZ SA, CEDRON-CHENG H.Massive Pulmonary Thromboembolism in a Patient with Crohn's Disease and Latent Tuberculosis Treated with Ustekinumab[J]. Rev Gastroenterol Peru, 2023, 43(3): 259-264.
[28] LOBUE P, MENZIES D.Treatment of Latent Tuberculosis Infection: an Update[J]. Respirology, 2010, 15(4): 603-622.
[29] OH JH, HAM SP, PARK HJ.Disseminated Tuberculosis in a Psoriasis Patient under Adalimumab Treatment Despite the Chemoprophylaxis of Latent Tuberculosis: a Case Report[J]. Ann Dermatol, 2021, 33(1): 77-81.