Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis.
Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis.
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DOI：
10.1080/14712598.2017.1263614
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发表时间：
2017-01
影响因子：
4.6
通讯作者：
Ritchlin CT
中科院分区：
文献类型：
--
作者：
Chiu YG;Ritchlin CT
类风湿性关节炎（RA）是一种慢性炎症性疾病，其特征是破骨细胞（OC）过度活性导致局灶性病理性骨吸收。核因子 kappa B 配体受体激活剂 (RANKL) 对于 OC 的增殖、分化和存活至关重要。 Denosumab (DMab) 是一种人源化单克隆抗体，以高亲和力与 RANKL 结合，并阻断其随后与 OC 前体表面的受体 RANK 的结合。作者回顾了 DMab 治疗应用的分子和细胞机制，提供了 DMab 药理学、功效和安全性的最新亮点，并讨论了 DMab 作为治疗类风湿性关节炎的新型治疗选择的潜力。临床结果表明，DMab 对 RA 的全身骨丢失和关节骨丢失均有效，且副作用有限。在服用皮质类固醇和双磷酸盐的 RA 患者中，骨侵蚀活动也有所减少。 DMab 与抗 TNF 药物的组合与感染率增加无关。总的来说，这些数据表明 DMab 与甲氨蝶呤以及可能的其他常规合成疾病修饰抗风湿药物 (csDMARD) 联合使用，是治疗 RA 的有效、安全且具有成本效益的选择。
Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by focal pathologic bone resorption due to excessive activity of osteoclasts (OC). Receptor activator of nuclear factor kappa B ligand (RANKL) is essential for the proliferation, differentiation, and survival of OC. Denosumab (DMab) is a humanized monoclonal antibody that binds to RANKL with high affinity and blocks its subsequent association with its receptor RANK on the surface of OC precursors. The authors review the molecular and cellular mechanisms underlying therapeutic applications of DMab, provide recent highlights on pharmacology, efficacy and safety of DMab, and discuss the potential of DMab as a novel therapeutic option for the treatment of rheumatoid arthritis. Clinical results suggest that DMab is efficient both in systemic and articular bone loss in RA with limited side effects. Diminished bone erosion activity was also noted in RA patients on corticosteroids and bisphosphonates. Combination of DMab with an anti-TNF agent was not associated with increased infection rates. Collectively, these data indicate that DMab, in combination with methotrexate and possibly other conventional synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs), is an effective, safe and cost-effective option for the treatment of RA.
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影响因子：
6.2
作者：
Chiu, Ya-Hui;Mensah, Kofi A.;Schwarz, Edward M.;Ju, Yawen;Takahata, Masahiko;Feng, Changyong;McMahon, Loralee A.;Hicks, David G.;Panepento, Ben;Keng, Peter C.;Ritchlin, Christopher T.
通讯作者：
Ritchlin, Christopher T.
DOI：
10.1634/theoncologist.2010-0154
发表时间：
2011
期刊：
The oncologist
影响因子：
--
作者：
Castellano D;Sepulveda JM;García-Escobar I;Rodriguez-Antolín A;Sundlöv A;Cortes-Funes H
通讯作者：
Cortes-Funes H
DOI：
10.1084/jem.189.7.1025
发表时间：
1999-04-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bachmann MF;Wong BR;Josien R;Steinman RM;Oxenius A;Choi Y
通讯作者：
Choi Y
影响因子：
32.4
作者：
Ashcroft, AJ;Cruickshank, SM;Carding, SR
通讯作者：
Carding, SR
影响因子：
3.9
作者：
Anandarajah, Allen;Thiele, Ralf;Ritchlin, Christopher T.
通讯作者：
Ritchlin, Christopher T.