Objective  To analyze the status and clinical characteristics of adverse drug reactions (ADRs) associated with ustekinumab and to provide a reference for clinical rational drug use.

Methods  PubMed, Web of Science, Embase, CNKI, WanFang Data, and the VIP Database were searched for ADRs of ustekinumab, and the collected literature was further analyzed statistically, including the basic information of patients, the use of drugs, the induction time of adverse reactions, clinical manifestations, treatment and outcomes.

Results  A total of 87 articles were collected, reporting 115 ADRs, involving 106 patients, including 53 males and 53 females. The average age of the patients was (44.28±18.28) years old. The main underlying diseases were psoriasis (54 cases, 50.95%) and Crohn's disease (42 cases, 39.62%). The ADRs mainly occurred within 1 year (76 cases, 66.08%) after therapy. ADRs of ustekinumab were mainly skin and accessory (21.58%) system injury, and followed by respiratory (16.11%), and nervous (13.07%) system injury. A total of 100 patients recovered or improved after receiving dose reduction, drug withdrawal or symptomatic treatment; 3 patients did not improve, 2 patients died, and 1 patient had no mention of improvement.

Conclusion  Clinicians and pharmacists should understand the characteristics of the ADRs of ustekinumab. More attention should be paid to ADRs of ustekinumab to ensure the safety of drug use.

1.Teng MWL, Bowman EP, McElwee JJ, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases[J]. Nat Med, 2015, 21(7): 719-729. DOI: 10.1038/nm.3895.

2.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. DOI: 10.1038/s41575-023-00768-1.

3.Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics[J]. J Am Acad Dermatol, 2019, 80(4): 1029-1072. DOI: 10.1016/j.jaad.2018.11.057.

4.Gossec L, Kerschbaumer A, Ferreira RJO, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update[J]. Ann Rheum Dis, 2024, 83(6): 706-719. DOI: 10.1136/ard-2024-225531.

5.中华医学会消化病学分会炎症性肠病学组, 中国炎症性肠病诊疗质量控制评估中心. 中国克罗恩病诊治指南 （2023年·广州）[J]. 中华消化杂志, 2024, 44(2): 100-132. [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]. Chinese Journal of Digestion, 2024, 44(2): 100-132.] DOI: 10.3760/cma.j.cn311367-20240109-00010.

6.中华医学会消化病学分会炎症性肠病学组, 中国炎症性肠病诊疗质量控制评估中心. 中国溃疡性结肠炎诊治指南（2023年·西安）[J]. 中华消化杂志, 2024, 44(2): 73-99. [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 ulcerative colitis (2023, Xi'an)[J]. Chinese Journal of Digestion, 2024, 44(2): 73-99.] DOI: 10.3760/cma.j.cn311367-20240125-00036.

7.Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions[J]. Clin Pharmacol Ther, 1981, 30(2): 239-245. DOI: 10.1038/clpt.1981.154.

8.Ma LL, Wang YY, Yang ZH, et al. Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: what are they and which is better?[J]. Mil Med Res, 2020, 7(1): 7. DOI: 10.1186/s40779-020-00238-8.

9.李柄辉, 訾豪, 李路遥, 等. 医学领域一次研究和二次研究的方法学质量（偏倚风险）评价工具[J]. 医学新知, 2021, 31(1): 51-58. [Li BH, Zi H, Li LY, et al. Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: what are they and which is better?[J]. Yixue Xinzhi Zazhi, 2021, 31(1): 51-58.] DOI: 10.12173/j.issn.1004-5511.2021.01.07.

10.Park SJ, Ahn GR, Park JW, et al. The first case of ustekinumab-associated hair repigmentation and a proposed mechanism of action[J]. Ann Dermatol, 2021, 33(3): 300-301. DOI: 10.5021/ad.2021.33.3.300.

11.Al Khalili A, Scott L, Dutz JP. New-onset autoantibody-mediated nephritis during ustekinumab therapy for psoriasis in patients with and without prior systemic lupus erythematosus[J]. JAAD Case Rep, 2019, 5(8): 682-685. DOI: 10.1016/j.jdcr.2019.05.022.

12.Makihara-Inukai M, Takeichi T, Ogawa-Momohara M, et al. Morphea in a Crohn's disease patient undergoing ustekinumab treatment[J]. Eur J of Dermatol, 2021, 31(1): 96-97. DOI: 10.1684/ejd.2020.3956.

13.Abdelnabi M, Elnawaa S, Benjanuwattra J, et al. Ustekinumab-induced fatal acute heart failure in a young female: a case report[J]. Methodist Debakey Cardiovasc J, 2022, 18(1): 54-58. DOI: 10.14797/mdcvj.1076.

14.Philippe L, Badie J, Faller JP, et al. Fatal thrombotic thrombocytopenic purpura in a psoriasis patient treated with ustekinumab and methotrexate[J]. Acta Derm Venereol, 2015, 95(4): 495-496. DOI: 10.2340/00015555-1987.

15.李彬彬, 许翠林, 胡乃中, 等. 临床药师参与1例克罗恩病合并多形红斑患者的药物治疗与监护[J]. 药物流行病学杂志, 2024, 33(9): 1074-1080. [Li BB, Xu CL, Hu NZ, et al. Clinical pharmacists participated in the drug therapy and pharmaceutical care of a patient with Crohn's disease complicated with erythema multiforme[J] Chinese Journal of Pharmacoepidemiology, 2024, 33(9): 1074-1080.] DOI: 10.12173/j.issn.1005-0698.202407014.

16.Napolitano M, Lembo L, Fania L, et al. Ustekinumab treatment of pityriasis rubra pilaris: a report of five cases[J]. J Dermatol, 2018, 45(2): 202-206. DOI: 10.1111/1346-8138.14114.

17.Mirouse A, Barete S, Desbois AC, et al. Long-term outcome of ustekinumab therapy for Behçet's disease[J]. Arthritis Rheumatol, 2019, 71(10): 1727-1732. DOI: 10.1002/art.40912.

18.Renoux MC, Dutronc S, Kollen L, et al. A case of disseminated tuberculosis in a child with Crohn's disease after treatment with azathioprine, adalimumab and ustekinumab[J]. Arch Bronconeumol, 2021, 57(8): 552-554. DOI: 10.1016/j.arbr.2020. 11.018.

19.Borrás-Blasco J, Cortes X, Fernandez-Martinez S, et al. Legionella pneumophila pneumonia possibly due to ustekinumab therapy in a patient with Crohn's disease[J]. Am J Health Syst Pharm, 2017, 74(4): 209-212. DOI: 10.2146/ajhp160010.

20.Anderson ME, Queen D, Vance SL, et al. Ustekinumab-associated disseminated verrucae[J]. JAAD Case Rep, 2018, 4(10): 1030-1033. DOI: 10.1016/j.jdcr.2018.08.014.

21.Shim HH, Cai SCS, Chan W, et al. Mycobacterium abscessus infection during ustekinumab treatment in Crohn's disease: a case report and review of the literature[J]. J Crohns Colitis, 2018, 12(12): 1505-1507. DOI: 10.1093/ecco-jcc/jjy126.

22.Miyachi H, Nakamura Y, Wakabayashi S, et al. Case of recurrent severe cellulitis and cutaneous candidiasis during psoriasis treatment with ustekinumab[J]. J Dermatol, 2017, 44(8): e206-e207. DOI: 10.1111/1346-8138.13884.

23.Koskinas J, Tampaki M, Doumba PP, et al. Hepatitis B virus reactivation during therapy with ustekinumab for psoriasis in a hepatitis B surface-antigen-negative anti-HBs-positive patient[J]. Br J Dermatol, 2013, 168(3): 679-680. DOI: 10.1111/bjd.12120.

24.Failla V, Nikkels AF. Ustekinumab and herpes zoster[J]. Dermatology, 2011, 222(2): 119-122. DOI: 10.1159/000323736.

25.Javadzadeh S, Gkini MA, Panos GD, et al. Ocular toxoplasmosis in a patient treated with ustekinumab for psoriasis[J].Clin Exp Dermatol, 2020, 45(6): 802-804. DOI: 10.1111/ced.14198.

26.Sunny J, Fonseca AG, Crim AM, et al. Hypersensitivity reaction to ustekinumab in pediatric and young adult inflammatory bowel disease patients: a case series[J]. JPGN Rep, 2022, 3(2): e205. DOI: 10.1097/pg9.0000000000000205.

27.Cohen B, Tomer G, Gavrilova T. Successful drug desensitization to ustekinumab in a patient with Crohn's disease[J]. Case Rep Gastroenterol, 2021, 15(2): 657-661. DOI: 10.1159/000516318.

28.Morais MR, Meneghello LP, de Oliveira CF, et al. Late reaction to ustekinumab infusion[J]. Dermatol Reports, 2013, 5(1): e2. DOI: 10.4081/dr.2013.e2.

29.Savvatis K, Pappritz K, Becher PM, et al. Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis after myocardial infarction [J]. Circ Heart Fail, 2014, 7(1): 161-171. DOI: 10.1161/CIRCHEARTFAILURE.113.000604.