Horneff G
Asklepios Kinderklinik St Augustin GmbH, Arnold-Janssen-Str 29, 53757 St Augustin.
Z Rheumatol. 2010 Aug;69(6):516-26. doi: 10.1007/s00393-010-0655-8.
Reports on malignancies observed in children exposed to TNF-inhibitors have raised questions about a potentially increased risk for lymphoma in particular. To date, the number of children exposed to biologicals is small. In addition, knowledge about the background incidence of malignancies in children with JIA and the influence of co-medication is limited.
Between 2001 and 2009 five cases of malignancy were documented in the German JIA Etanercept in Children Registry covering 1200 patients, including one case each of non-Hodgkin's lymphoma, Hodgkin's lymphoma, thyroid cancer, yolk sac cancer, and cervical dysplasia. All five patients had been treated with a number of other drugs including cytotoxic drugs (methotrexate, leflunomide, azathioprine, cyclosporine A) before institution of etanercept therapy. All patients were treated with etanercept, while two patients were also treated with adalimumab or infliximab. Malignancy appeared after an etanercept treatment period of between 3 weeks and more than 6 years. At the time of diagnosis, three patients were still on etanercept, five on methotrexate and one on infliximab. In three patients malignancy first occurred in adulthood. All patients recovered.
This case series of JIA and malignancy shows that prior to starting treatment with TNF-inhibitors careful consideration needs to be given to the possible benefits and risks. Patients need to be observed long-term and observation should to be continued in adulthood. Although a temporal association has been described to date, a causal role of TNF inhibitors cannot be excluded and parents and/or patients should be appropriately informed about this risk.
关于接触肿瘤坏死因子抑制剂(TNF - 抑制剂)的儿童中观察到的恶性肿瘤报告,尤其引发了关于淋巴瘤潜在风险增加的问题。迄今为止,接触生物制剂的儿童数量较少。此外,关于幼年特发性关节炎(JIA)患儿恶性肿瘤的背景发病率以及联合用药影响的知识有限。
在2001年至2009年期间,德国儿童JIA依那西普注册登记处记录了1200例患者中的5例恶性肿瘤病例,包括非霍奇金淋巴瘤、霍奇金淋巴瘤、甲状腺癌、卵黄囊癌和宫颈发育异常各1例。所有5例患者在开始使用依那西普治疗前均接受过多种其他药物治疗,包括细胞毒性药物(甲氨蝶呤、来氟米特、硫唑嘌呤、环孢素A)。所有患者均接受了依那西普治疗,其中2例患者还接受了阿达木单抗或英夫利昔单抗治疗。恶性肿瘤在依那西普治疗3周后至6年多后出现。诊断时,3例患者仍在使用依那西普,5例在使用甲氨蝶呤,1例在使用英夫利昔单抗。3例患者的恶性肿瘤首次发生在成年期。所有患者均康复。
这个JIA与恶性肿瘤的病例系列表明,在开始使用TNF - 抑制剂治疗之前,需要仔细权衡可能的益处和风险。患者需要长期观察,成年后也应继续观察。尽管迄今为止已描述了时间上的关联,但不能排除TNF抑制剂的因果作用,应适当告知家长和/或患者这种风险。