Desai Sheetal B, Furst Daniel E
Department of Rheumatology, University of California, Los Angeles, CA 90095-1670, USA.
Best Pract Res Clin Rheumatol. 2006 Aug;20(4):757-90. doi: 10.1016/j.berh.2006.06.002.
Worldwide, over 400,000 patients have been treated with tumour necrosis factor (TNF)-alpha antagonists for indications that include rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis and ankylosing spondylitis. Since their approval, concerns regarding safety have been raised. There is a risk of re-activation of granulomatous diseases, especially tuberculosis, and measures should be taken for detection and treatment of latent tuberculosis infections. Preliminary data suggest that anti-TNF therapy may be safe in chronic hepatitis C. However, TNF-alpha antagonists have resulted in re-activation of chronic hepatitis B if not given concurrently with antiviral therapy. Solid tumours do not appear to be increased with anti-TNF therapy. Variable rates of increased lymphoma risk have been described with anti-TNF therapy compared with the general population, although no increased risk was found compared with a rheumatoid arthritis population. Large phase II and III trials with TNF-alpha antagonists in advanced heart failure have shown trends towards a worse prognosis, and should therefore be avoided in this population. Both etanercept and infliximab are associated with the formation of autoantibodies, and these autoantibodies are rarely associated with any specific clinical syndrome. Rare cases of aplastic anaemia, pancytopenia, vasculitis and demyelination have been described with anti-TNF therapy. This chapter will discuss the safety profile and adverse events of the three commercially available TNF-alpha antagonists: etanercept, infliximab and adalimumab. The data presented in this review have been collected from published data, individual case reports or series, package inserts, the Food and Drug Administration postmarketing adverse events surveillance system, and abstracts from the American College of Rheumatology and European Congress of Rheumatology meetings for 2005.
在全球范围内，超过40万名患者接受了肿瘤坏死因子（TNF）-α拮抗剂治疗，其适应症包括类风湿性关节炎、青少年类风湿性关节炎、炎症性肠病、银屑病关节炎和强直性脊柱炎。自其获批以来，人们对其安全性提出了担忧。存在肉芽肿性疾病重新激活的风险，尤其是结核病，应采取措施检测和治疗潜伏性结核感染。初步数据表明，抗TNF治疗在慢性丙型肝炎中可能是安全的。然而，如果不与抗病毒治疗同时使用，TNF-α拮抗剂会导致慢性乙型肝炎重新激活。抗TNF治疗似乎不会使实体瘤增加。与普通人群相比，抗TNF治疗的淋巴瘤风险增加率各不相同，尽管与类风湿性关节炎人群相比未发现风险增加。在晚期心力衰竭患者中使用TNF-α拮抗剂的大型II期和III期试验显示出预后更差的趋势，因此该人群应避免使用。依那西普和英夫利昔单抗均与自身抗体形成有关，且这些自身抗体很少与任何特定临床综合征相关。抗TNF治疗曾有再生障碍性贫血、全血细胞减少、血管炎和脱髓鞘的罕见病例报道。本章将讨论三种市售TNF-α拮抗剂（依那西普、英夫利昔单抗和阿达木单抗）的安全性概况和不良事件。本综述中的数据收集自已发表的数据、个案报告或系列报道、药品说明书、美国食品药品监督管理局上市后不良事件监测系统，以及2005年美国风湿病学会和欧洲风湿病学会会议的摘要。
