Abstract：
BACKGROUND: Progressive multiple sclerosis (PMS) is a debilitating condition characterized by progressively worsening symptoms. Monoclonal antibodies are novel therapies for MS, but their safety and efficacy in the progressive form have not been comprehensively studied. In this systematic review, we aimed to evaluate the available evidence regarding monoclonal antibody treatment for PMS.
METHODS: After registration of the study protocol in PROSPERO, we systematically searched three major databases for clinical trials involving monoclonal antibodies administration for PMS treatment. All the retrieved results were imported into the EndNote reference manager. After removing the duplicates, two independent researchers did the study selection and data extraction. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist.
RESULTS: Of the 1846 studies in the preliminary search, 13 clinical trials investigating monoclonal antibodies (Ocrelizumab, Natalizumab, Rituximab, and Alemtuzumab) in PMS patients were included. Ocrelizumab was significantly effective in reducing clinical disease progression measures in primary PMS patients. The results for Rituximab were not completely reassuring and only showed significant changes for some endpoints on MRI and clinical measures. Natalizumab decreased the relapse rate and improved MRI features for secondary PMS patients, but not clinical endpoints. The studies on Alemtuzumab treatment revealed conflicting outcomes, with improvements observed in MRI endpoints but clinical worsening in patients. Additionally, among the studied adverse events, upper respiratory infections, urinary tract infections, and nasopharyngitis were frequently reported.
CONCLUSIONS: Based on our findings, Ocrelizumab is the most efficient monoclonal antibody for primary PMS, although it is associated with a higher risk of infection. While other monoclonal antibodies did not show significant promise in treating PMS, more research is necessary.
METHODS: After registration of the study protocol in PROSPERO, we systematically searched three major databases for clinical trials involving monoclonal antibodies administration for PMS treatment. All the retrieved results were imported into the EndNote reference manager. After removing the duplicates, two independent researchers did the study selection and data extraction. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist.
RESULTS: Of the 1846 studies in the preliminary search, 13 clinical trials investigating monoclonal antibodies (Ocrelizumab, Natalizumab, Rituximab, and Alemtuzumab) in PMS patients were included. Ocrelizumab was significantly effective in reducing clinical disease progression measures in primary PMS patients. The results for Rituximab were not completely reassuring and only showed significant changes for some endpoints on MRI and clinical measures. Natalizumab decreased the relapse rate and improved MRI features for secondary PMS patients, but not clinical endpoints. The studies on Alemtuzumab treatment revealed conflicting outcomes, with improvements observed in MRI endpoints but clinical worsening in patients. Additionally, among the studied adverse events, upper respiratory infections, urinary tract infections, and nasopharyngitis were frequently reported.
CONCLUSIONS: Based on our findings, Ocrelizumab is the most efficient monoclonal antibody for primary PMS, although it is associated with a higher risk of infection. While other monoclonal antibodies did not show significant promise in treating PMS, more research is necessary.
摘要：
背景：进行性多发性硬化症（PMS）是一种衰弱的疾病，其特征是症状逐渐恶化。单克隆抗体是MS的新疗法，但其渐进形式的安全性和有效性尚未得到全面研究。在这次系统审查中，我们旨在评估有关单克隆抗体治疗PMS的现有证据.
方法：在PROSPERO注册研究方案后，我们系统地检索了3个主要数据库,寻找涉及单克隆抗体用于PMS治疗的临床试验.所有检索到的结果都已导入到EndNote引用管理器中。删除重复项后，两名独立研究人员进行了研究选择和数据提取.使用JoannaBriggs研究所（JBI）清单评估偏倚风险。
结果：在初步搜索中的1846项研究中，13项研究单克隆抗体的临床试验(Ocrelizumab，那他珠单抗,利妥昔单抗,包括PMS患者中的Alemtuzumab）。Ocrelizumab在降低原发性PMS患者的临床疾病进展方面显着有效。利妥昔单抗的结果并不能完全令人放心，仅在MRI和临床测量的某些终点方面显示出明显的变化。那他珠单抗降低了继发性PMS患者的复发率并改善了MRI特征，但不是临床终点。关于Alemtuzumab治疗的研究揭示了相互矛盾的结果，观察到MRI终点的改善，但患者的临床恶化。此外,在研究的不良事件中，上呼吸道感染,尿路感染,和鼻咽炎经常报告。
结论：根据我们的发现，Ocrelizumab是用于原发性PMS的最有效的单克隆抗体，尽管它与较高的感染风险有关。虽然其他单克隆抗体在治疗PMS方面没有显示出显著的前景，更多的研究是必要的。
方法：在PROSPERO注册研究方案后，我们系统地检索了3个主要数据库,寻找涉及单克隆抗体用于PMS治疗的临床试验.所有检索到的结果都已导入到EndNote引用管理器中。删除重复项后，两名独立研究人员进行了研究选择和数据提取.使用JoannaBriggs研究所（JBI）清单评估偏倚风险。
结果：在初步搜索中的1846项研究中，13项研究单克隆抗体的临床试验(Ocrelizumab，那他珠单抗,利妥昔单抗,包括PMS患者中的Alemtuzumab）。Ocrelizumab在降低原发性PMS患者的临床疾病进展方面显着有效。利妥昔单抗的结果并不能完全令人放心，仅在MRI和临床测量的某些终点方面显示出明显的变化。那他珠单抗降低了继发性PMS患者的复发率并改善了MRI特征，但不是临床终点。关于Alemtuzumab治疗的研究揭示了相互矛盾的结果，观察到MRI终点的改善，但患者的临床恶化。此外,在研究的不良事件中，上呼吸道感染,尿路感染,和鼻咽炎经常报告。
结论：根据我们的发现，Ocrelizumab是用于原发性PMS的最有效的单克隆抗体，尽管它与较高的感染风险有关。虽然其他单克隆抗体在治疗PMS方面没有显示出显著的前景，更多的研究是必要的。
