Ocrelizumab治疗对PPMS残疾患者上肢功能的影响:ORATORIO研究的亚组结果为ORATORIO- hand研究设计提供参考(P3.2-091)

摘要目的:从ORATORIO III期研究中评估ocrelizumab对更多残疾/老年原发性进行性多发性硬化(PPMS)患者上肢功能的疗效(NCT01194570)，为iii期ib ORATORIO-HAND研究的设计提供资料。

背景:在ORATORIO(扩展残疾状态量表[EDSS]≤6.5)中，Ocrelizumab与安慰剂相比，在减少上肢功能障碍(9孔Peg测试[9HPT])方面表现出了疗效。Ocrelizumab对更多不符合纳入ORATORIO的残疾PPMS患者的获益将满足未满足的需求。

设计/方法:ORATORIO pms患者(N=732;eds 3.0 - -6.5;年龄18-55岁)随机(2:1)接受ocrelizumab或安慰剂治疗≥120周，直到发生预先指定数量的EDSS进展事件。在基线亚组:EDSS≥6.0 (N=220)，年龄>岁45岁(N=384)， 9HPT时间>25秒(N=434)中，ocrelizumab预防上肢功能进展的疗效(通过12周证实9HPT恶化20%(双手平均)进行了研究。

结果:Ocrelizumab减少了更多残疾/老年PPMS患者上肢残疾的进展。基线EDSS评分<6.0和≥6.0的患者9HPT进展的风险降低与安慰剂相似(40% vs 38%， p=0.92)，基线9HPT时间≤25s和>25s (49% vs 44%， p=0.82)。进展事件主要发生在9HPT >25秒vs≤25秒的患者中(安慰剂:34.3% vs 17.8%;Ocrelizumab: 21.5% vs 9.9%);观察到≤45岁患者比> - 45岁患者疗效更好的弱趋势(p=0.29)。

结论:ORATORIO-HAND旨在进一步研究ocrelizumab对上肢功能的疗效。根据ORATORIO观察到的9HPT进展率，1000名符合条件的患者(EDSS 3.0─8.0，年龄18-65岁，9HPT >25秒)随机(1:1)接受ocrelizumab或安慰剂治疗≥120周(直到预先指定的进展事件发生)，将能够评估ocrelizumab对确认的9HPT进展的疗效(主要终点)。放映将于2019年第一季度开始。

披露:Giovannoni博士曾在AbbVie、Biogen、Novartis、Teva Neuroscience和Roche Diagnostics Corporation的咨询、科学顾问委员会服务、演讲或其他活动中获得个人报酬。他还为默克-雪兰诺、健赞-赛诺菲、Synthon BV的顾问委员会会议、医师峰会和几次医学教育会议收取咨询费。Giovannoni博士在《多发性硬化症和相关疾病》(Elsevier)的编辑职位上获得了个人报酬。Giovannoni博士获得了Takeda Pharmaceutical Company的研究支持。Airas博士曾因咨询、科学顾问委员会服务、演讲或与Roche, Merck公司的其他活动而获得个人报酬。Airas博士获得了Sanofi-Genzyme的研究支持。Bove博士曾在Roche Genentech和Genzyme Sanofi的咨询、科学顾问委员会服务、演讲或其他活动中获得个人报酬。Bove博士获得了Akili Interactive的研究支持。他在Biogen, Schering, Merck, TEVA, Novartis, Sanofi-Genzyme, Actelion, Biocad, Generium的咨询、科学顾问委员会服务、演讲或其他活动中获得个人报酬。Cutter博士曾因咨询、担任科学顾问委员会成员、演讲或参与AMO Pharmaceuticals、Biolinerx、Horizon Pharmaceuticals、Hisun Pharmaceuticals、Merck、Merck/Pfizer、Opko Biologics、Neurim、Novartis、Ophazyme、赛诺菲-安卫特、Reata Pharmaceuticals、Receptos/Celgene、Teva Pharmaceuticals、NHLBI、NICHD、Atara Biotherapeutics、Axon、Biogen、Argenix、Brainstorm Cell Therapeutics、Charleston Labs Inc、Click Therapeutics等活动而获得个人报酬， Genzyme, Genentech, GW Pharma, Klein-Buendel Incorporated, Medimmune, Medday, Novartis, Roche, Scifluor, Somahlution, Teva pharmaceuticals, TG Therapeutics, UT Houston. Dr. Cutter has received personal compensation in an editorial capacity for Statistical editor for the Journal of the American Society of Nephrology. Dr. Cutter has received research support from Via MGFA. Dr. Hobart has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda, Asubio, Bayer Schering, Biogen Idec, F. Hoffmann-La Roche Ltd, Genzyme, Merck Serono, Novartis, Oxford PharmaGenesis, Oxford Health Policy Forum and Teva. Dr. Kuhle’s institution has received compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis Pharmaceuticals, Protagen AG, Roche, Teva, Sanofi Genzyme, Swiss MS Society, and Merck Serono,. Dr. Kuhle has received research support from ECTRIMS Research Fellowship Programme, Bayer AG, Biogen, Sanofi Genzyme, Merck, Novartis Pharmaceuticals, Roche, Swiss MS Society, Swiss National Research Foundation, and University of Basel. Dr. Oh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EMD-Serono, Novartis, Biogen-Idec, Sanofi-Genzyme, Roche, Celgene. Dr. Oh has received research support from Biogen-Idec, Sanofi-Genzyme. Dr. Tur has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Bayer, F. Hoffmann-La Roche Ltd, Ismar Healthcare, Merck Serono, Novartis, Sanofi and Teva. Dr. Tur has received research support from Postdoctoral research ECTRIMS Fellowships. Dr. Garas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Dr. Model has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Dr. Manfrini has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd as an employee. Dr. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes, Actelion, Acorda Therapeutics, Celgene, EMD Serono, GeNeuro, GW Pharma, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, Sanofi Genzyme, PlatformQ Health Education, PRIME, and Strategic Consultants Intl. Dr. Wolinsky has received royalty, license fees, or contractual rights payments from UTHealth to Millipore (Chemicon International) Corporation.