Nanau Radu M, Neuman Manuela G
In Vitro Drug Safety and Biotechnology.
J Pharm Pharm Sci. 2014;17(3):324-61. doi: 10.18433/j3wp4f.
Inflammatory and rheumatic arthritis remain leading causes of disability worldwide. The arthritis therapeutic area commands the largest market for the prescription of biological and non-steroidal anti-inflammatory drugs (NSAID). Yet biotechnology and pharmaceutical companies conducting research and providing therapeutics in this area frequently face challenges in patient safety. The purpose of our study was to assess safety of anti-tumor necrosis factor therapies in arthritis patients.
The present study systematically reviews adverse events of biologicals alone or in the presence of NSAIDs and other immunosuppressant therapeutics such as disease-modifying antirheumatic drugs (DMARD). We assessed the rheumatology literature that included clinical trials with anti-tumor necrosis factor (TNF) biologicals and case reports published between 2010 and 2014.
Currently approved anti-TNF biologicals in arthritis include the monoclonal antibodies infliximab, adalimumab, certolizumab pegol and golimumab, and the fusion protein etanercept. The most frequently-reported adverse event was infection. We grouped the adverse reactions as immune-mediated, hypersensitivity syndrome reactions including cutaneous and hepatic manifestation, neurological, hematological, and malignancy.
Most adverse events are due to the failure of host immunological control, which involves susceptibility to the drug itself, or de novo infection or reactivation of a latent bacterial or viral infection, often with a different expression of disease. Drug-induced liver injury associated with anti-TNF biologicals must be kept in mind when evaluating patients with increased liver enzymes.
Risk assessment in individuals undergoing treatment with biologicals represents a step towards achieving a personalized medicine approach to identify those patients that will safely benefit from this therapeutic approach. Patients and physicians must be alert of anti-TNF agents as potential causes of drug-induced liver injury and monitor the therapies. Personalizing therapeutic pharmacovigilance promises to optimize benefits while minimizing side effects.
炎症性和风湿性关节炎仍是全球致残的主要原因。关节炎治疗领域占据生物制剂和非甾体抗炎药（NSAID）处方的最大市场。然而，在该领域开展研究并提供治疗方法的生物技术和制药公司在患者安全方面经常面临挑战。我们研究的目的是评估抗肿瘤坏死因子疗法在关节炎患者中的安全性。
本研究系统回顾了生物制剂单独使用或与NSAID及其他免疫抑制疗法（如改善病情抗风湿药（DMARD））联合使用时的不良事件。我们评估了2010年至2014年间发表的包括抗肿瘤坏死因子（TNF）生物制剂临床试验和病例报告的风湿病学文献。
目前已批准用于关节炎的抗TNF生物制剂包括单克隆抗体英夫利昔单抗、阿达木单抗、聚乙二醇化赛妥珠单抗和戈利木单抗，以及融合蛋白依那西普。最常报告的不良事件是感染。我们将不良反应分为免疫介导的、包括皮肤和肝脏表现的过敏综合征反应、神经学的、血液学的和恶性肿瘤的。
大多数不良事件是由于宿主免疫控制失败，这涉及对药物本身的易感性，或新发感染或潜伏细菌或病毒感染的重新激活，通常伴有不同的疾病表现。在评估肝酶升高的患者时，必须牢记与抗TNF生物制剂相关的药物性肝损伤。
对接受生物制剂治疗的个体进行风险评估是朝着实现个性化医疗方法迈出的一步，以确定那些将从这种治疗方法中安全获益的患者。患者和医生必须警惕抗TNF药物作为药物性肝损伤的潜在原因，并监测治疗。个性化治疗药物警戒有望在使副作用最小化的同时优化益处。
