Rubbert-Roth Andrea, Perniok Andreas
Med. Klinik I der Universität zu Köln, Joseph-Stelzmann-Str. 9, 50924 Köln, Germany.
Z Rheumatol. 2003 Aug;62(4):367-77. doi: 10.1007/s00393-003-0545-4.
New treatment strategies in rheumatoid arthritis are targeted to interfere with critical mediators of inflammation. Proinflammatory cytokines like IL-1 beta and TNFalpha play a crucial role in induction and maintenance of synovitis, pannus formation and bone and cartilage destruction. Within a few years, these morphological changes may lead to joint destruction and consecutively to functional impairment. Since April 2002 a recombinant human interleukin-1 receptor antagonist (Anakinra) is available in Germany for treatment of patients with rheumatoid arthritis. Anakinra (Kineret(R)) is approved for therapy in combination with methotrexate and should be applied according to guidelines established by the German Rheumatology Society for the use of biologicals in treatment of patients with rheumatoid arthritis. The approval of anakinra as a new therapeutic is based on data obtained in large multicenter, placebo-controlled, and randomised trials in comparison to placebo. Treatment of Anakinra as monotherapy or in combination with methotrexate lead to significant improvement of signs and symptoms of disease as measured by the ACR 20 (or more) response and was associated with a slower radiographic progression with regard to joint space narrowing and development of erosions. Anakinra showed a favourable safety profile with injection side reactions as the predominant side effect that occurs in 70% of patients usually after 10-12 days of treatment and that are mostly mild to moderate and self-limiting. Patients with previous pneumonia or other risk factors for pulmonary infections such as chronic obstructive lung disease seem to show a slightly increased risk of developing infectious complications of the bronchopulmonary system while being on anakinra and should be monitored appropriately. Combining IL-1ra treatment with the use of anti-TNF agents showed an increased risk of infectious complications in clinical studies and is not recommended at present. Studies are currently assessing the use of anakinra for treatment of other rheumatic diseases like psoriatic arthritis, juvenile arthritis or spondylarthropathy.
类风湿关节炎的新治疗策略旨在干扰炎症的关键介质。白细胞介素-1β和肿瘤坏死因子α等促炎细胞因子在滑膜炎、血管翳形成以及骨和软骨破坏的诱导和维持中起关键作用。在几年内，这些形态学变化可能导致关节破坏，并继而导致功能障碍。自2002年4月起，重组人白细胞介素-1受体拮抗剂（阿那白滞素）在德国可用于治疗类风湿关节炎患者。阿那白滞素（凯纷）被批准与甲氨蝶呤联合治疗，应按照德国风湿病学会制定的生物制剂治疗类风湿关节炎患者的指南使用。阿那白滞素作为一种新疗法的获批基于与安慰剂相比在大型多中心、安慰剂对照和随机试验中获得的数据。阿那白滞素单药治疗或与甲氨蝶呤联合治疗可使疾病体征和症状通过美国风湿病学会20%（或更高）反应得到显著改善，并且与关节间隙狭窄和侵蚀发展方面较慢的放射学进展相关。阿那白滞素显示出良好的安全性，注射部位反应是主要副作用，70%的患者通常在治疗10 - 12天后出现，大多为轻至中度且为自限性。既往有肺炎或其他肺部感染风险因素（如慢性阻塞性肺疾病）的患者在使用阿那白滞素时似乎发生支气管肺系统感染并发症的风险略有增加，应进行适当监测。在临床研究中，白细胞介素-1受体拮抗剂治疗与抗肿瘤坏死因子药物联合使用显示感染并发症风险增加，目前不建议使用。目前正在研究评估阿那白滞素用于治疗其他风湿性疾病，如银屑病关节炎、幼年特发性关节炎或脊柱关节病。
