Department of Medicine, Faculty of Medicine, Kuwait University, PO Box 24923, Al-Safat 13110, Kuwait.
Clin Rheumatol. 2012 Sep;31(9):1281-7. doi: 10.1007/s10067-012-2040-2. Epub 2012 Aug 9.
Over the last decade, biologic therapeutic proteins have advanced the treatment of diseases such as rheumatoid arthritis (RA). Therapeutic antibodies such as infliximab, adalimumab, rituximab, tocilizumab, golimumab, certolizumab pegol, the receptor construct etanercept, and abatacept, an anticluster of differentiation (CD)80/anti-CD86 fusion protein, are used as treatment for RA and ankylosing spondylitis (AS). Infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept are inhibitors of tumor necrosis factor (TNF), a key regulator of inflammation. Left untreated, progression of rheumatic diseases due to inflammation can lead to irreversible joint damage and serious disability. One limitation for the use of therapeutic antibodies is immunogenicity, the induction of antibodies by the adaptive immune system in response to foreign substances. The development of antidrug antibodies (ADAs) has a varying impact on the clinical efficacy of biologic agents for the treatment of RA and AS, depending on whether the ADAs are neutralizing or non-neutralizing. Studies have indicated that neutralizing ADAs are associated with a reduced efficacy, decreased drug survival, increased instances of dose escalation, and adverse events. Comparison studies of anti-TNF biologics have demonstrated that each drug has a different sustained efficacy profile depending on immunogenicity. The purpose of this review is to provide rheumatologists with information regarding the effect of neutralizing antibodies on the sustainable efficacy of anti-TNF biologic therapies. This information will be of value to practicing rheumatologists in Africa and the Middle East who should take into account the potential for changes in the efficacy and safety of biologic therapies and closely monitor patients under their care.
在过去的十年中，生物治疗蛋白已经推动了类风湿关节炎（RA）等疾病的治疗进展。治疗性抗体，如英夫利昔单抗、阿达木单抗、利妥昔单抗、托珠单抗、戈利木单抗、培塞利珠单抗、受体构建体依那西普和abatacept（一种抗 CD80/抗 CD86 融合蛋白），被用于治疗 RA 和强直性脊柱炎（AS）。英夫利昔单抗、阿达木单抗、戈利木单抗、培塞利珠单抗和依那西普是肿瘤坏死因子（TNF）的抑制剂，TNF 是炎症的关键调节剂。如果不进行治疗，炎症引起的风湿性疾病的进展可能导致不可逆转的关节损伤和严重残疾。治疗性抗体的使用受限之一是免疫原性，即适应性免疫系统对异物产生抗体的诱导。抗药物抗体（ADA）的产生对生物制剂治疗 RA 和 AS 的临床疗效有不同的影响，这取决于 ADA 是中和性的还是非中和性的。研究表明，中和性 ADA 与疗效降低、药物存活期缩短、剂量升级增加和不良事件有关。抗 TNF 生物制剂的比较研究表明，每种药物的持续疗效谱因免疫原性而异。本文的目的是为风湿病学家提供有关中和抗体对抗 TNF 生物疗法可持续疗效的影响的信息。这一信息对非洲和中东的临床医生具有价值，他们应该考虑到生物疗法的疗效和安全性可能发生变化，并密切监测他们治疗的患者。
