Department of Rheumatology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute (IDIVAL), Santander, Spain
Department of Rheumatology, Mid & South Essex NHS Foundation Trust, Southend University Hospital, Westcliff-on-Sea, United Kingdom.
Pol Arch Intern Med. 2021 Feb 26;131(2):171-181. doi: 10.20452/pamw.15438. Epub 2020 Jun 18.
The progress in the understanding of the pathophysiology of rheumatic diseases provided a rational basis for the development of biologic disease‑modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), which have completely revolutionized the treatment of inflammatory conditions. These agents differ in terms of their effectiveness for controlling specific rheumatic diseases depending on the pivotal cytokine driving the inflammatory process. Cytokine blockers were the first to be developed and rapidly expanded. They include agents that act against tumor necrosis factor α (TNF‑α) (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol) and interleukin (IL) 6 (tocilizumab and sarilumab), IL‑1 (anakinra, canakinumab, and rilonacept), IL‑17 (secukinumab and ixekizumab), and IL-12/23 (ustekinumab) receptors. Lymphocyte‑targeting agents include rituximab and belimumab, which act against B cells by different mechanisms, and abatacept, which is a T cell costimulation modulator. tsDMARDs, also known as small‑molecule inhibitors, are oral drugs based on a novel strategy to treat inflammatory diseases. Janus kinase (JAK) inhibitors (tofacitinib, baricitinib, and upadacitinib) and phosphodiesterase 4 inhibitors (apremilast) form this group. The major concern with the use of bDMARDs and tsDMARDs is a higher risk of infections. Performance of blood tests as well as screening for tuberculosis and hepatitis viral infection are mandatory prior to biologic therapy initiation. Adherence to an immunization program is also recommended. Whenever possible, the choice of bDMARDs and tsDMARDs should be guided by the patient's comorbidities. There have been limited data on the use of these drugs during pregnancy, but anti‑TNF‑α therapy, rituximab, and anakinra seem to be safe. Biologic agents are expensive, but biosimilars have emerged as a cost‑effective option with a potential to treat a greater number of patients.
风湿性疾病病理生理学研究的进展为生物改善病情抗风湿药物（bDMARDs）和靶向合成改善病情抗风湿药物（tsDMARDs）的开发提供了合理依据，这彻底改变了炎症性疾病的治疗方法。这些药物在控制特定风湿性疾病方面的有效性因驱动炎症过程的关键细胞因子而异。细胞因子阻滞剂是最早开发并迅速扩展的药物。它们包括针对肿瘤坏死因子-α（TNF-α）（依那西普、英夫利昔单抗、阿达木单抗、戈利木单抗和 Certolizumab Pegol）和白细胞介素（IL）-6（托珠单抗和 Sarilumab）、IL-1（阿那白滞素、卡那单抗和 Rilonacept）、IL-17（Secukinumab 和 Ixekizumab）和 IL-12/23（Ustekinumab）受体的药物。淋巴细胞靶向药物包括通过不同机制作用于 B 细胞的利妥昔单抗和贝利木单抗，以及作为 T 细胞共刺激调节剂的阿巴西普。tsDMARDs，也称为小分子抑制剂，是基于治疗炎症性疾病的新策略的口服药物。Janus 激酶（JAK）抑制剂（托法替尼、巴瑞替尼和 Upadacitinib）和磷酸二酯酶 4 抑制剂（阿普米司特）属于这一组。bDMARDs 和 tsDMARDs 使用的主要关注点是感染风险增加。在开始生物治疗之前，必须进行血液检查以及筛查结核和肝炎病毒感染。建议患者也遵循免疫接种计划。在可能的情况下，bDMARDs 和 tsDMARDs 的选择应根据患者的合并症来指导。关于这些药物在怀孕期间的使用数据有限，但抗 TNF-α 治疗、利妥昔单抗和阿那白滞素似乎是安全的。生物制剂价格昂贵，但生物类似药的出现提供了一种具有成本效益的选择，并有可能治疗更多的患者。
