Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis The VELOCE study
Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis The VELOCE study
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DOI：
10.1212/wnl.0000000000010380
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发表时间：
2020-10-06
期刊：
影响因子：
9.9
通讯作者：
Traboulsee, Anthony
中科院分区：
文献类型：
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作者：
Bar-Or, Amit;Calkwood, Jonathan C.;Traboulsee, Anthony
评价Ocrelizumab对复发型多发性硬化受试者免疫应答的影响的IIIb A期研究（VEGFCE）（NCT 02545868）评估了ocrelizumab（OCR）治疗的复发性多发性硬化患者对选定疫苗的反应。（n = 68; OCR 600 mg）或对照组（n = 34;干扰素β或无疾病改善治疗）。所有患者均接受了含破伤风类毒素（TT）的疫苗、Pneumovax（23价肺炎球菌多糖疫苗[ 23-PPV]）和匙孔血蓝蛋白（KLH）。随机分组时，OCR组再分为OCR 1（n = 33）和OCR 2（n = 35）。OCR 1组在23-PPV后4周接受Prevnar（13价结合肺炎球菌疫苗）; OCR 2组和对照组接受流感疫苗。免疫接种开始后12周开始OCR启动（OCR组）或在第1天（对照组）。结果TT疫苗在8周的阳性反应率为23.9%，在OCR与54.5%的对照组。第4周时，OCR组对23-PPV ≥ 5种血清型的阳性应答率为71.6%，对照组为100%。Prevnar与Pneumovax一样，不能增强对肺炎球菌血清型的反应。与对照组相比，OCR组对KLH的体液反应降低。率在4周内对5个流感病毒株的范围从55.6%至80.0%在OCR 2组和75.0%至97.0%在control group.ConclusionPeripherally B细胞耗尽OCR收件人安装衰减的体液反应，临床相关的疫苗和新抗原KLH，这表明使用标准的非活疫苗，而对OCR治疗仍然是一个考虑因素。对于季节性流感疫苗，建议接种OCR患者，因为即使减弱，也可以预期潜在的保护性体液应答。证据分类本研究提供了II类证据，证实OCR治疗后复发性多发性硬化症患者对非活疫苗的体液应答与未治疗或干扰素β治疗的患者相比减弱，但它们仍有保护作用
ObjectiveThe phase IIIb A Study to Evaluate the Effects of Ocrelizumab on Immune Responses in Participants With Relapsing Forms of Multiple Sclerosis (VELOCE) study (NCT02545868) assessed responses to selected vaccines in ocrelizumab (OCR)- treated patients with relapsing multiple sclerosis.MethodsPatients were randomized 2: 1 into the OCR group ( n = 68; OCR 600 mg) or control group (n = 34; interferon beta or no disease- modifying therapy). All received tetanus toxoid (TT)- containing vaccine, Pneumovax (23- valent pneumococcal polysaccharide vaccine [ 23-PPV]), and keyhole limpet hemocyanin ( KLH). The OCR group was subdivided into OCR1 (n = 33) and OCR2 (n = 35) at randomization. The OCR1 group received Prevnar (13-valent conjugate pneumococcal vaccine) 4 weeks after 23-PPV; the OCR2 and control groups received influenza vaccine. Vaccinations started 12 weeks after OCR initiation (OCR group) or on day 1 (control group).ResultsPositive response rate to TT vaccine at 8 weeks was 23.9% in the OCR vs 54.5% in the control group. Positive response rate to >= 5 serotypes in 23-PPV at 4 weeks was 71.6% in the OCR and 100% in the control group. Prevnar did not enhance response to pneumococcal serotypes in common with Pneumovax. Humoral response to KLH was decreased in the OCR vs control group. rates at 4 weeks against 5 influenza strains ranged from 55.6% to 80.0% in the OCR2 group and 75.0% to 97.0% in the control group.ConclusionPeripherally B-cell-depleted OCR recipients mounted attenuated humoral responses to clinically relevant vaccines and the neoantigen KLH, suggesting that use of standard nonlive vaccines while on OCR treatment remains a consideration. For seasonal influenza vaccines, it is recommended to vaccinate patients on OCR because a potentially protective humoral response, even if attenuated, can be expected.Classification of evidenceThis study provides Class II evidence confirming that the humoral response to nonlive vaccines in patients with relapsing multiple sclerosis after OCR treatment is attenuated compared with untreated or interferon beta-treated patients, but they can still be expected to be protective.