Department of Neurology (M.R., K.F., M.K.,P.A., H.P.H., S.G.M., O.A.), Medical Faculty, Heinrich Heine University Düsseldorf; Department of Neurology (M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich Heine University Düsseldorf; Department of Neurology (I.A., A.G., K.H., R.G., I.K.), St. Josef-Hospital, Ruhr University Bochum, Germany; Department of Neurology (I.A.), Sechenov First Moscow State Medical University, Russia; Department of Neurology (G.L.), Johanna Etienne Hospital, Neuss, Germany; Department of Neurology (G.N.), San Martino Hospital, Genova, Italy; Neuroimmunology and MS Research (H.H.K., S.S.), Department of Neurology, University Hospital Zürich, Switzerland; Department of Neurology (P.S.R., B.K., T.Z.), Medical University of Vienna, Austria; Department of Neurology (D.B., J.C.), B4 unit, CRC-SEP, Toulouse Purpan University Hospital, France; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity) (D.B., J.C.) INSERM UMR1291-CNRS UMR5051 - Université Toulouse III, France; Aix Marseille University (B.A.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France; Technical University of Munich (A.B., K.G.), School of Medicine, Department of Neurology, Klinikum rechts der Isar, Germany; University of Lille (H.Z.), Inserm, CRC-SEP, CHU Lille, France; Institute of Clinical Neuroimmunology (T.K.), Faculty of Medicine, Ludwig Maximilian University, Munich; Department of Neurology (R.B., J.R.), Asklepios Klinik Altona, Hamburg; Department of Neurology and Institute of Neuroimmunology and MS (INIMS) (V.H.), University Medical Center Hamburg-Eppendorf, Germany; APHM, Hôpital de la Timone (J.P.S.), CEMEREM; Aix Marseille Univ, CNRS, CRMBM (J.P.S), UMR 7339, Marseille, France; Department of Neurology (D.W., A.J.), The Walton Centre, Liverpool, United Kingdom; the Cleveland Clinic Abu Dhabi, (A.J.) UAE; Department of Neurology (M.K.), Alfried Krupp Hospital, Essen, Germany; Department of Neurology (A.G.,R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris, France; Department of Neurology (A.B.), Universitätsklinikum Augsburg; Department of Neurology (M.W.H., C.T.), Hannover Medical School; Department of Neurology (A.H.), University of Würzburg; Molecular Neuroimmunology Group (S.J., B.W.), Department of Neurology, University of Heidelberg; Department of Neurology (M.G.), University hospital Greifswald; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (N.S., F.P), Max Delbrueck Center for Molecular Medicine and Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health; Department of Neurology (K.R.), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin; Department of Neurology (N.C.), University Hospital Strasbourg; Service de neurologie (R.M.), sclérose en plaques, pathologies de la myéline et neuro-inflammation - Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Department of Neurology (M.L.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of General Pediatrics (M.K.), Neonatology and Pediatric Cardiology, University Children's Hospital, Medical Faculty, Heinrich Heine University Düsseldorf; Department of Neurology (M.D.), University Hospital, Münster; and Marianne-Strauß-Klinik (I.K.), Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg, Germany.
Neurol Neuroimmunol Neuroinflamm. 2021 Nov 16;9(1). doi: 10.1212/NXI.0000000000001100. Print 2022 Jan.
To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti-interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD).
Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab.
Patients received TCZ for 23.8 months (median; interquartile range 13.0-51.1 months), with an IV dose of 8.0 mg/kg (median; range 6-12 mg/kg) every 31.6 days (mean; range 26-44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5-5) to 0 (range 0-0.9; = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0-5] to 0 [range 0-4.2]; < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0-3.0] to 0.2 [range 0-2.0]; = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD ( = 0.04; for the brain) and in AQP4-IgG+ NMOSD ( < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy.
This study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.
评估托珠单抗（TCZ），一种人源化抗白细胞介素-6 受体抗体，在髓鞘少突胶质细胞糖蛋白-IgG 相关疾病（MOGAD）和视神经脊髓炎谱系疾病（NMOSD）中的长期安全性和疗效。
回顾性评估了 57 例 MOGAD（n=14）、水通道蛋白 4（AQP4）-IgG 阳性（n=36）和血清阴性 NMOSD（n=7；12%）患者的年复发率（ARR）、扩展残疾状况量表评分、MRI、自身抗体滴度、疼痛和不良事件，这些患者在先前的免疫治疗（特别是利妥昔单抗）后转为 TCZ。
患者接受 TCZ 治疗 23.8 个月（中位数；四分位距 13.0-51.1 个月），静脉滴注剂量为 8.0mg/kg（中位数；范围 6-12mg/kg），每 31.6 天（平均；范围 26-44 天）一次。对于 MOGAD，ARR 从 1.75（范围 0.5-5）降至 0（范围 0-0.9； = 0.0011）。AQP4-IgG+（ARR 从 1.5[范围 0-5]降至 0[范围 0-4.2]；<0.001）和血清阴性 NMOSD（从 3.0[范围 1.0-3.0]降至 0.2[范围 0-2.0]； = 0.031）也出现了类似的效果。在 TCZ 治疗期间，所有患者中有 60%（MOGAD 为 79%，AQP4-IgG+为 56%，血清阴性 NMOSD 为 43%）无复发。残疾随访表明病情稳定。MOGAD（ = 0.04；脑）和 AQP4-IgG+ NMOSD（<0.001；脊髓）的 MRI 炎症活动减少。慢性疼痛没有变化。对于仅接受 TCZ 治疗至少 12 个月的患者（n=44），ARR 减少得到了确认，包括 MOGAD 亚组（n=11）和 AQP4-IgG+患者亚组（n=28）。同样，在接受 TCZ 治疗至少 12 个月的患者中，59%无复发，MOGAD 为 73%，AQP4-IgG+为 57%，血清阴性 NMOSD 为 40%。未观察到严重或意外的安全信号。与 TCZ 单药治疗相比，附加治疗并未显示出优势。
这项研究提供了 III 级证据，表明长期 TCZ 治疗是安全的，并降低了 MOGAD 和 AQP4-IgG+ NMOSD 中的复发概率。
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