Sepriano Alexandre, Regel Andrea, van der Heijde Désirée, Braun Jürgen, Baraliakos Xenofon, Landewé Robert, Van den Bosch Filip, Falzon Louise, Ramiro Sofia
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.
Rheumazentrum Ruhrgebiet, Ruhr-University Bochum , Herne , Germany.
RMD Open. 2017 Jan 27;3(1):e000396. doi: 10.1136/rmdopen-2016-000396. eCollection 2017.
To update the evidence for the efficacy and safety of (b)biological and (ts)targeted-synthetic disease-modifying anti-rheumatic drugs (DMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2016 update of the Assessment of SpondyloArthritis international Society/European League Against Rheumatism (ASAS/EULAR) recommendations for the management of axSpA.
Systematic literature review (2009-2016) for randomised controlled trials (RCT), including long-term extensions, strategy trials and observational studies (the latter was only for safety assessment and a comparator was required). Interventions were any bDMARD or tsDMARD. All relevant efficacy and safety outcomes were included.
76 papers and 24 abstracts fulfilled the inclusion criteria. Large treatment effects were found both in radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) for all tumour necrosis factor inhibitors (TNFi) (NNT to achieve ASAS40 response ranged between 2.6-5.2 for r-axSpA and 2.3-5.4 for nr-axSpA). For nr-axSpA, efficacy was superior for those who had objective signs of inflammation (positive C reactive protein or inflammation on MRI-SI). Secukinumab 150 mg has shown efficacy in two phase 3 RCTs (NNT to achieve ASAS40 response: 3.4 and 4.0). Ustekinumab and tofacitinib have shown positive results in phase 2/proof-of-concept trials; trials with apremilast, rituximab, interleukin (IL)-6 antagonists and abatacept have failed their primary end points. New (unknown) safety signals were not found in the trials but long-term observational safety data for TNFi are still scarce.
New evidence supports the efficacy and safety of TNFi both in r-axSpA and nr-axSpA. Secukinumab is the first drug targeting the IL-17 pathway in r-axSpA that has shown efficacy.
更新（生物）生物制剂和（靶向）合成改善病情抗风湿药（DMARDs）治疗中轴型脊柱关节炎（axSpA）患者的疗效和安全性证据，以为2016年更新的脊柱关节炎国际协会/欧洲抗风湿病联盟（ASAS/EULAR）中轴型脊柱关节炎管理建议提供参考。
对随机对照试验（RCT）进行系统文献回顾（2009 - 2016年），包括长期延长期试验、策略试验和观察性研究（后者仅用于安全性评估且需要有对照）。干预措施为任何生物DMARD或靶向合成DMARD。纳入所有相关的疗效和安全性结局。
76篇论文和24篇摘要符合纳入标准。在影像学中轴型脊柱关节炎（r - axSpA）和非影像学中轴型脊柱关节炎（nr - axSpA）中，所有肿瘤坏死因子抑制剂（TNFi）均显示出显著的治疗效果（r - axSpA达到ASAS40反应的NNT范围为2.6 - 5.2，nr - axSpA为2.3 - 5.4）。对于nr - axSpA，有炎症客观体征（C反应蛋白阳性或MRI - SI有炎症）的患者疗效更佳。司库奇尤单抗150mg在两项3期RCT中显示出疗效（达到ASAS40反应的NNT分别为3.4和4.0）。乌司奴单抗和托法替布在2期/概念验证试验中显示出阳性结果；阿普斯特、利妥昔单抗、白细胞介素（IL）-6拮抗剂和阿巴西普的试验未达到其主要终点。试验中未发现新的（未知的）安全信号，但TNFi的长期观察性安全数据仍然匮乏。
新证据支持TNFi在r - axSpA和nr - axSpA中的疗效和安全性。司库奇尤单抗是首个在r - axSpA中显示出疗效的靶向IL - 17通路的药物。
