Rein Philipp, Mueller Ruediger B
Division of Rheumatology, Immunology and Rehabilitation, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Rheumatol Ther. 2017 Dec;4(2):247-261. doi: 10.1007/s40744-017-0073-3. Epub 2017 Aug 22.
Management and therapy of rheumatoid arthritis (RA) has been revolutionized by the development and approval of the first biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumor necrosis factor (TNF) α at the end of the last century. Today, numerous efficacious agents with different modes of action are available and achievement of clinical remission or, at least, low disease activity is the target of therapy. Early therapeutic interventions aiming at a defined goal of therapy (treat to target) are supposed to halt inflammation, improving symptoms and signs, and preserving structural integrity of the joints in RA. Up to now, bDMARDs approved for therapy in RA include agents with five different modes of action: TNF inhibition, T cell co-stimulation blockade, IL-6 receptor inhibition, B cell depletion, and interleukin 1 inhibition. Furthermore, targeted synthetic DMARDs (tsDMARDs) inhibiting Janus kinase (JAK) and biosimilars also are approved for RA. The present review focuses on bDMARDs and tsDMARDS regarding similarities and possible drug-specific advantages in the treatment of RA. Furthermore, compounds not yet approved in RA and biosimilars are discussed. Following the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) recommendations, specific treatment of the disease will be discussed with respect to safety and efficacy. In particular, we discuss the question of favoring specific bDMARDs or tsDMARDs in the two settings of insufficient response to methotrexate and to the first bDMARD, respectively.
上世纪末,首款靶向肿瘤坏死因子(TNF)α的生物改善病情抗风湿药(bDMARDs)的研发与获批,彻底改变了类风湿关节炎(RA)的管理与治疗方式。如今,有多种作用方式不同的有效药物可供使用,实现临床缓解或至少达到低疾病活动度是治疗的目标。旨在实现明确治疗目标(达标治疗)的早期治疗干预措施,理应能够抑制RA中的炎症,改善症状和体征,并保持关节的结构完整性。到目前为止,获批用于RA治疗的bDMARDs包括具有五种不同作用方式的药物:TNF抑制、T细胞共刺激阻断、IL-6受体抑制、B细胞清除和白细胞介素1抑制。此外,抑制Janus激酶(JAK)的靶向合成改善病情抗风湿药(tsDMARDs)以及生物类似药也获批用于RA治疗。本综述重点关注bDMARDs和tsDMARDs在RA治疗中的相似之处及可能的药物特异性优势。此外,还将讨论尚未在RA中获批的化合物以及生物类似药。遵循美国风湿病学会(ACR)和欧洲抗风湿病联盟(EULAR)的建议,将从安全性和有效性方面讨论该疾病的具体治疗方法。特别是,我们将分别讨论在对甲氨蝶呤反应不足和对首个bDMARD反应不足的两种情况下,更倾向于使用特定bDMARDs或tsDMARDs的问题。