背景:Ocrelizumab是一种常用的抗CD20单克隆抗体,可有效治疗复发缓解型(RRMS)和原发性进行性(PPMS)多发性硬化症。在需要助行器或轮椅的运动障碍程度较高的MS患者中使用奥利珠单抗的现实世界并未得到很好的表征,因为这些人群被排除在初始研究之外。较高的残疾水平可能是获得治疗的障碍。本研究旨在描述访问,在现实世界中,奥利珠单抗在高度残疾的MS患者中的耐受性和治疗结果。
方法:作为正在进行的奥克瑞珠单抗治疗研究的一部分,障碍,以及布莱根MS中心MS患者的结果,我们回顾性分析了所有开始服用奥克瑞珠单抗时扩展残疾状态量表(EDSS)≥6.5的患者.在这项研究开始之前,所有患者都由他们的治疗提供者开始服用奥利珠单抗。患者因近期利妥昔单抗暴露而被排除,与一种以上的免疫抑制剂共同治疗,或导致高EDSS的替代诊断。数据收集了奥克瑞珠单抗副作用的发生率和严重程度,持续治疗超过一年,和MS稳定与进展,而在这种治疗。
结果:在2017年至2021年期间使用奥利珠单抗的1219例患者中,113例(9.3%)在开始奥利珠单抗时EDSS为6.5或更高。在113人中,51人(45.1%)被排除:6人(5.3%),因为他们是重复的或没有在我们中心接受奥克瑞珠单抗,25(22.1%),由于上一年的利妥昔单抗治疗,16(14.2%)由于缺乏至少1年的随访,和4(3.5%),由于相关的合并症/与其他免疫抑制剂的治疗。62例患者纳入最终分析。在奥克雷珠单抗开始时,平均年龄为62.1+/-8.7岁,EDSS中位数为7.0(范围为6.5~9.5).由于客观的临床疾病恶化,纳入的62例患者中有26例(41.9%)开始使用Ocrelizumab,17例(27.4%)由于主观恶化,在8(12.9%),以防止未来的进展。32名患者(51.6%)在整个研究期间继续服用奥利珠单抗,奥利珠单抗的平均使用时间为36.5+/-17.0个月。29名患者(46.8%)在研究期间没有出现副作用。29例(46.7%)患者停止治疗,其中,9(31.0%)列举了一个以上的停药原因:17(58.6%)列举了副作用,12人(41.4%)提到进展/缺乏益处,6人(20.7%)提到了Covid19大流行,1人(3.4%)将财务问题作为中止的原因。在研究过程中,16例(25.8%)患者因EDSS导致残疾恶化,5人(8.1%)残疾改善,而41人(66.1%)保持稳定,最终EDSS中位数为7.0(范围为6.5至9.5)。重要的是,18例患者(29.0%)在服用奥克瑞珠单抗时报告主观疾病稳定性。
结论:Ocrelizumab可能导致部分高度残疾MS患者的疾病稳定,但在这一高危患者人群中,可能的获益需要与不良事件的发生率谨慎相平衡.
BACKGROUND: Ocrelizumab is a commonly used anti-CD20 monoclonal antibody with efficacy in the treatment of both relapsing-remitting (RRMS) and primary
progressive (PPMS) multiple sclerosis. Real world use of ocrelizumab in MS patients with higher levels of motor disability requiring a walker or a wheelchair is not well characterized as these populations were excluded from initial studies. Higher levels of disability may be a barrier to treatment access. This study aimed to describe the access to, and tolerability and therapeutic outcomes of ocrelizumab in highly disabled MS patients in a real-world setting.
METHODS: As part of an ongoing study of ocrelizumab treatment access, barriers, and outcomes in MS patients at the Brigham MS Center, we retrospectively reviewed all patients with an Expanded Disability Status Scale (EDSS) of 6.5 or greater at the time of ocrelizumab initiation. All patients were started on ocrelizumab by their treating providers prior to this study initiation. Patients were excluded for recent rituximab exposure, co-treatment with more than one immunosuppressant, or alternative diagnoses contributing to high EDSS. Data was collected on incidence and severity of side effects while on ocrelizumab, persistence of treatment beyond one year, and MS stabilization versus progression while on this treatment.
RESULTS: Of the 1219 patients on ocrelizumab between 2017 and 2021, 113 (9.3 %) had EDSS of 6.5 or greater at the time of ocrelizumab initiation. Of the 113, 51 (45.1 %) were excluded: 6 (5.3 %) because they were duplicates or didn\'t receive ocrelizumab at our center, 25 (22.1 %) due to rituximab treatment in the previous year, 16 (14.2 %) due to lack of at least 1 year of follow up, and 4 (3.5 %) due to relevant comorbidities/treatment with other immunosuppressants. 62 patients were included in the final analysis. At ocrelizumab start, mean age was 62.1 +/- 8.7 years and median EDSS was 7.0 (range 6.5 to 9.5). Ocrelizumab was started in 26 of the included 62 patients (41.9 %) because of objective clinical disease worsening, in 17 (27.4 %) because of subjective worsening, in 8 (12.9 %) to prevent future progression. 32 patients (51.6 %) continued ocrelizumab throughout the study period, with average length of ocrelizumab use of 36.5 +/- 17.0 months. 29 patients (46.8 %) experienced no side effects during the study period. 29 (46.7 %) patients discontinued treatment, and of those, 9 (31.0 %) cited more than one reason for discontinuation: 17 (58.6 %) cited side effects, 12 (41.4 %) cited progression/lack of benefit, 6 (20.7 %) cited the Covid19 pandemic, and 1 (3.4 %) cited financial issues as a reason for discontinuation. Over the course of the study, 16 (25.8 %) patients had disability worsening by EDSS, 5 (8.1 %) had disability improvement, and 41 (66.1 %) remained stable, with a median end EDSS of 7.0 (range 6.5 to 9.5). Importantly, 18 patients (29.0 %) reported subjective disease stability while on ocrelizumab.
CONCLUSIONS: Ocrelizumab may lead to disease stabilization in a subset of highly disabled MS patients, but possible benefits need to be carefully balanced against the incidence of adverse events in this high-risk patient population.