Li Mingming, You Ruxu, Su Yuyong, Zhou Hongbo, Gong Shiwei
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Pharmacol. 2023 Jul 24;14:1169327. doi: 10.3389/fphar.2023.1169327. eCollection 2023.
Tumor necrosis factor (TNF) inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab pegol) have revolutionized the treatment of severe immune-mediated inflammatory diseases, including rheumatoid arthritis, Crohn's disease, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis. This study assessed adverse drug reactions (ADRs) after the use of TNFα inhibitors in VigiAccess of the World Health Organization (WHO) and compared the adverse reaction characteristics of five inhibitors to select the drug with the least risk for individualized patient use. The study was a retrospective descriptive analysis method in design. We sorted out five marketed anti-TNFα drugs, and their ADR reports were obtained from WHO-VigiAccess. Data collection included data on the age groups, sex, and regions of patients worldwide covered by ADR reports, as well as data on disease systems and symptoms caused by ADRs recorded in annual ADR reports and reports received by the WHO. By calculating the proportion of adverse reactions reported for each drug, we compared the similarities and differences in adverse reactions for the five drugs. Overall, 1,403,273 adverse events (AEs) related to the five anti-TNFα agents had been reported in VigiAccess at the time of the search. The results show that the 10 most commonly reported AE manifestations were rash, arthralgia, rheumatoid arthritis, headache, pneumonia, psoriasis, nausea, diarrhea, pruritus, and dyspnea. The top five commonly reported AE types of anti-TNFα drugs were as follows: infections and infestations (184,909, 23.0%), musculoskeletal and connective tissue disorders (704,657, 28.6%), gastrointestinal disorders (122,373, 15.3%), skin and subcutaneous tissue disorders (108,259, 13.5%), and nervous system disorders (88,498, 11.0%). The preferred terms of myelosuppression and acromegaly were obvious in golimumab. Infliximab showed a significantly higher ADR report ratio in the infusion-related reaction compared to the other four inhibitors. The rate of ADR reports for lower respiratory tract infection and other infections was the highest for golimumab. No causal associations could be established between the TNFα inhibitors and the ADRs. Current comparative observational studies of these inhibitors revealed common and specific adverse reactions in the ADR reports of the WHO received for these drugs. Clinicians should improve the rational use of these high-priced drugs according to the characteristics of ADRs.
肿瘤坏死因子（TNF）抑制剂（阿达木单抗、英夫利昔单抗、依那西普、戈利木单抗和赛妥珠单抗）彻底改变了包括类风湿性关节炎、克罗恩病、银屑病关节炎、强直性脊柱炎和溃疡性结肠炎在内的严重免疫介导性炎症疾病的治疗方法。本研究评估了世界卫生组织（WHO）的VigiAccess中使用TNFα抑制剂后的药物不良反应（ADR），并比较了五种抑制剂的不良反应特征，以选择个体患者使用风险最低的药物。该研究在设计上采用回顾性描述性分析方法。我们整理出五种已上市的抗TNFα药物，其ADR报告来自WHO-VigiAccess。数据收集包括ADR报告所涵盖的全球患者的年龄组、性别和地区数据，以及年度ADR报告和WHO收到的报告中记录的ADR所导致的疾病系统和症状数据。通过计算每种药物报告的不良反应比例，我们比较了这五种药物不良反应的异同。总体而言，在搜索时，VigiAccess中已报告了1,403,273例与五种抗TNFα药物相关的不良事件（AE）。结果显示，最常报告的10种AE表现为皮疹、关节痛、类风湿性关节炎、头痛、肺炎、银屑病、恶心、腹泻、瘙痒和呼吸困难。抗TNFα药物最常报告的前五种AE类型如下：感染和寄生虫感染（184,909例，23.0%）、肌肉骨骼和结缔组织疾病（704,657例，28.6%）、胃肠道疾病（122,373例，15.3%）、皮肤和皮下组织疾病（108,259例，13.5%）以及神经系统疾病（88,498例，11.0%）。戈利木单抗中骨髓抑制和肢端肥大症的首选术语明显。与其他四种抑制剂相比，英夫利昔单抗在输液相关反应中的ADR报告率显著更高。戈利木单抗的下呼吸道感染和其他感染的ADR报告率最高。无法在TNFα抑制剂与ADR之间建立因果关联。目前对这些抑制剂的比较观察性研究揭示了WHO收到的这些药物的ADR报告中的常见和特定不良反应。临床医生应根据ADR的特征提高这些高价药物的合理使用。
