奥瑞珠单抗治疗复发型多发性硬化症五年：OPERA研究开放标签扩展
Five years of ocrelizumab in relapsing multiple sclerosis: OPERA studies open-label extension.
作者信息
Hauser Stephen L, Kappos Ludwig, Arnold Douglas L, Bar-Or Amit, Brochet Bruno, Naismith Robert T, Traboulsee Anthony, Wolinsky Jerry S, Belachew Shibeshih, Koendgen Harold, Levesque Victoria, Manfrini Marianna, Model Fabian, Hubeaux Stanislas, Mehta Lahar, Montalban Xavier
机构信息
From the Department of Neurology (S.L.H.), University of California, San Francisco; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, University of Basel, Switzerland; NeuroRx Research (D.L.A.); Departments of Neurology and Neurosurgery (D.L.A.), McGill University, Montreal, Canada; Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (A.B.-O.), University of Pennsylvania, Philadelphia; Department of Neurology (B.B.), CHU de Bordeaux, France; Department of Neurology (R.T.N.), Washington University School of Medicine, St. Louis, MO; Division of Neurology (A.T.), Department of Medicine, University of British Columbia, Vancouver, Canada; Department of Neurology (J.S.W.), McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth); F. Hoffmann-La Roche Ltd (S.B., H.K., M.M., F.M., S.H.), Basel, Switzerland; Genentech, Inc. (V.L., L.M.), South San Francisco, CA; Division of Neurology (X.M.), University of Toronto, Canada; and Department of Neurology-Neuroimmunology (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain. During completion of the work related to this article, S.B. and L.M. were employees of F. Hoffmann-La Roche Ltd; current affiliations are Biogen (S.B.), Cambridge, MA; and Alder Biopharmaceuticals Inc. (L.M.), Bothell, WA.
出版信息
Neurology. 2020 Sep 29;95(13):e1854-e1867. doi: 10.1212/WNL.0000000000010376. Epub 2020 Jul 20.
OBJECTIVE
To assess over 3 years of follow-up the effects of maintaining or switching to ocrelizumab (OCR) therapy on clinical and MRI outcomes and safety measures in the open-label extension (OLE) phase of the pooled OPERA: I/II studies in relapsing multiple sclerosis.
METHODS
After 2 years of double-blind, controlled treatment, patients continued OCR (600 mg infusions every 24 weeks) or switched from interferon (IFN)-β-1a (44 μg 3 times weekly) to OCR when entering the OLE phase (3 years). Adjusted annualized relapse rate, time to onset of 24-week confirmed disability progression (CDP)/improvement (CDP), brain MRI activity (gadolinium-enhanced and new/enlarging T2 lesions), and percentage brain volume change were analyzed.
RESULTS
Of patients entering the OLE phase, 88.6% completed year 5. The cumulative proportion with 24-week CDP was lower in patients who initiated OCR earlier vs patients initially receiving IFN-β-1a (16.1% vs 21.3% at year 5; = 0.014). Patients continuing OCR maintained and those switching from IFN-β-1a to OCR attained near complete and sustained suppression of new brain MRI lesion activity from years 3-5. Over the OLE phase, patients continuing OCR exhibited less whole brain volume loss from double-blind study baseline vs those switching from IFN-β-1a (-1.87% vs -2.15% at year 5; < 0.01). Adverse events were consistent with past reports and no new safety signals emerged with prolonged treatment.
CONCLUSION
Compared with patients switching from IFN-β-1a, earlier and continuous OCR treatment up to 5 years provided sustained benefit on clinical and MRI measures of disease progression.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that earlier and continuous treatment with OCR provided sustained benefit on clinical and MRI outcomes of disease activity and progression compared with patients switching from IFN-β-1a. The study is rated Class III because of the initial treatment randomization disclosure that occurred after inclusion in OLE.
CLINICAL TRIAL IDENTIFIERS
NCT01247324/NCT01412333.
目的
在复发型多发性硬化症的OPERA I/II合并研究的开放标签扩展（OLE）阶段，通过超过3年的随访评估维持或换用奥瑞珠单抗（OCR）治疗对临床、MRI结果及安全指标的影响。
方法
经过2年的双盲对照治疗后，患者进入OLE阶段（3年），继续接受OCR治疗（每24周静脉输注600 mg）或从干扰素（IFN）-β-1a（每周3次，每次44 μg）换用OCR治疗。分析调整后的年化复发率、24周确认残疾进展（CDP）/改善（CDP）的发病时间、脑MRI活性（钆增强及新的/扩大的T2病变）以及脑体积变化百分比。
结果
进入OLE阶段的患者中，88.6%完成了第5年的研究。与最初接受IFN-β-1a治疗的患者相比，更早开始使用OCR治疗的患者24周CDP的累积比例更低（第5年时分别为16.1%和21.3%；P = 0.014）。继续接受OCR治疗的患者以及从IFN-β-1a换用OCR治疗的患者在第3至5年新脑MRI病变活性几乎完全且持续受到抑制。在OLE阶段，与从IFN-β-1a换用OCR治疗的患者相比，继续接受OCR治疗的患者全脑体积较双盲研究基线时减少得更少（第5年时分别为-1.87%和-2.15%；P < 0.01）。不良事件与既往报告一致，长期治疗未出现新的安全信号。
结论
与从IFN-β-1a换用OCR治疗的患者相比，早期及持续使用OCR治疗长达5年在疾病进展的临床和MRI指标方面提供了持续的益处。
证据分级
本研究提供了III级证据，表明与从IFN-β-1a换用OCR治疗的患者相比，早期及持续使用OCR治疗在疾病活动和进展的临床及MRI结果方面提供了持续的益处。该研究被评为III级是因为纳入OLE后初始治疗随机分组情况被披露。
临床试验标识符
NCT01247324/NCT01412333
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