抗 CD20 治疗药物初治原发性进展型多发性硬化症：一项多中心真实世界研究。
Anti-CD20 Therapies in Drug-Naive Patients With Primary Progressive Multiple Sclerosis: A Multicenter Real-Life Study.
机构信息
From the Neurology Department (M.H., A.K., G.E., E.L.P., L. Michel), Rennes University Hospital; Clinical Neuroscience Centre (M.H., A.K., G.E., E.L.P., L. Michel), CIC_P1414 INSERM, Rennes, University Hospital, Rennes University; Université Claude Bernard Lyon 1 (F.R., R.C., S.V.), Université de Lyon; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (F.R., R.C., S.V.), Hospices Civils de Lyon, Bron; Observatoire Français de la Sclérose en Plaques (F.R., R.C., S.V.), Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292; EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis, state-approved foundation (F.R., R.C., S.V.), Bron; Department of Neurology (G.M.), Nancy University Hospital; Université de Lorraine (G.M.), Inserm, INSPIIRE, Nancy; MS Unit (P.L.), CHU de Montpellier; University of Montpellier (MUSE) (P.L.); Department of Neurology and Clinical Investigation Center (J.D.S.), CHU de Strasbourg, CIC 1434, INSERM 1434; Service de Neurologie (D.-A.L.), CHU Nantes, Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, CIC INSERM 1413; Department of Neurology (C.P.), Fondation Rotschild, Paris; Department of Neurology (T.M.), CHU de Dijon, EA4184; Department of Neurology (E.T.), Nimes University Hospital; IGF (E.T.), University of Montpellier, CNRS, INSERM; CHU de Caen (G.D.), MS Expert Centre, Department of Neurology, Normandy University, Caen; Neurology (C.L.-F.), UR2CA_URRIS, Centre Hospitalier Universitaire Pasteur2, Université Nice Côte d'Azur, Nice; Department of Neurology (J.C.), CHU de Toulouse, CRC-SEP; Université Toulouse III (J.C.), Infinity, INSERM UMR1291-CNRS UMR5051; Service de Neurologie (E.B.), CHU de Besançon; Sorbonne Universités (B.S.), Paris Brain Institute, ICM, Inserm UMR S 1127, CNRS UMR 7225, and Department of Neurology, AP-HP, Hôpital de la Pitié Salpêtrière; CHU Clermont-Ferrand (P.C.), CRC SEP Auvergne, Department of Neurology, and INSERM NeuroDol U1107; Département de Neurologie (E.M.), Hôpital Pitié-Salpêtrière, APHP; Centre de Ressources et de Compétences SEP Paris (E.M.); Departement of Neurology (O.H.), Centre de Ressource et Compétences SEP IDF Ouest, Hôpital de Poissy; CHU Lille (H.Z.), CRCSEP Lille, Univ Lille, U1172; Department of Neurology (A.R.), University Hospital of Bordeaux; Neurocentre Magendie (A.R.), Bordeaux University, INSERM U1215; Department of Neurology (O.C.), CHU Grenoble Alpes, Neurology MS Clinic Grenoble, Grenoble Alpes University Hospital, La Tronche; Department of Neurology (S.M.), CHU de Reims, CRC-SEP; Department of Neurology (A.A.-K.), CHU d'Amiens; Departement of Neurology (B.B.), CHU de Rouen; Service de Neurologie (J.P.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Aix Marseille Univ; Department of Neurology (L. Magy), Hôpital Dupuytren, CHU de Limoges; Department of Neurology (J.-P.N.), Hôpital Jean Bernard, CHU La Milétrie, Poitiers; Department of Neurology (J.-P.C.), Hôpital Nord, CHU de Saint-Étienne; CRC SEP and Department of Neurology (I.D.), Hôpital Bretonneau, CHU de Tours; Department of Neurology (A.W.), Hôpital Henri Mondor, APHP, Créteil; Department of Neurology (M.T.), Hôpital Foch, Suresnes; Department of Neurology (C.L.), CHU Bicêtre; and Department of Neurology (K.H.), Hôpital Pierre Delafontaine, Centre Hospitalier de Saint-Denis, France.
出版信息
Neurology. 2024 Oct 22;103(8):e209886. doi: 10.1212/WNL.0000000000209886. Epub 2024 Sep 25.
BACKGROUND AND OBJECTIVES
Although rituximab failed to demonstrate a significant effect on disability progression in primary progressive multiple sclerosis (PPMS), ocrelizumab succeeded. Our main objective was to analyze confirmed disability progression (CDP) in a cohort of patients with PPMS treated with anti-CD20 therapies compared with a weighted untreated control cohort.
METHODS
This was a retrospective study using data from the French MS registry (Observatoire Français de la Sclérose En Plaques). We included patients with PPMS treated or never treated with anti-CD20 therapies from 2016 to 2021, with an Expanded Disability Status Scale score of ≤6.5 at baseline. The primary outcome was time to first CDP. The secondary outcomes were time to first relapse, MRI activity at 2 years, identification of risk factors associated with CDP, and serious infection incidence rates (IIRs). Each outcome was studied using an inverse probability of treatment weighting method. The outcomes were modeled using a weighted proportional Cox model for the time-to-event outcomes and by a logistic regression regarding the MRI activity.
RESULTS
A total of 1,184 patients (426 treated and 758 untreated) fulfilled the inclusion criteria. Median age (Q1-Q3) was 56 years (49.3-63.8), and 52.7% were female. Among treated patients, 295 received rituximab, whereas 131 received ocrelizumab. At baseline, anti-CD20-treated patients were younger (median 51.9 vs 58.6 years, Cohen = 0.683) and had more active disease (54.5 vs 27.8%, Cohen = 0.562). 91.6% were drug-naive at inclusion. In time to first CDP analysis, no statistical significance was observed (hazard ratio [HR], 1.13; 95% CI 0.93-1.36, = 0.2113). In time to first relapse analysis, a nonsignificant trend toward fewer patients relapsing in the treated group was observed (HR 0.83; 95% CI 0.48-1.28, = 0.0809). For MRI activity, no significant difference was found between the 2 groups. Risk factors associated with CDP in the treated group were male sex and MS duration. IIR was 6.67 (95% CI 3.12-14.25) per 100 person-years in the treated group vs 2.67 (95% CI 0.80-8.86) in the untreated group.
DISCUSSION
Time to first CDP was not different between anti-CD20 treated and untreated patients with PPMS. Although our study is retrospective and mainly included patients treated by rituximab, our results indicate that there should be a constant evaluation of all available data to ascertain the best risk/benefit ratio for patients with PPMS.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that anti-CD20 therapy of previously untreated patients with PPMS was not superior to no therapy in delaying time to first CDP.
背景与目的
虽然利妥昔单抗未能显示对原发性进展型多发性硬化症（PPMS）的残疾进展有显著影响，但奥瑞珠单抗成功了。我们的主要目的是分析接受抗 CD20 治疗的 PPMS 患者队列与加权未治疗对照队列相比确认的残疾进展（CDP）。
方法
这是一项使用法国多发性硬化症登记处（Observatoire Français de la Sclérose En Plaques）数据的回顾性研究。我们纳入了 2016 年至 2021 年接受或未接受抗 CD20 治疗的 PPMS 患者，基线时扩展残疾状况量表（EDSS）评分≤6.5。主要结局是首次 CDP 的时间。次要结局是首次复发的时间、2 年时的 MRI 活动、确定与 CDP 相关的危险因素以及严重感染发生率（IIR）。每个结局均使用逆概率治疗加权法进行研究。结局通过加权比例风险 Cox 模型进行时间事件结局建模，通过逻辑回归进行 MRI 活动建模。
结果
共有 1184 名患者（426 名接受治疗，758 名未接受治疗）符合纳入标准。中位年龄（Q1-Q3）为 56 岁（49.3-63.8），52.7%为女性。在接受治疗的患者中，295 名接受了利妥昔单抗治疗，131 名接受了奥瑞珠单抗治疗。基线时，接受抗 CD20 治疗的患者年龄较小（中位年龄 51.9 岁 vs 58.6 岁，Cohen's d = 0.683），疾病更活跃（54.5% vs 27.8%，Cohen's d = 0.562）。91.6%的患者入组时未接受过药物治疗。在首次 CDP 时间分析中，未观察到统计学意义（风险比[HR]，1.13；95%CI 0.93-1.36， = 0.2113）。在首次复发时间分析中，观察到治疗组复发患者的趋势较少，但无统计学意义（HR 0.83；95%CI 0.48-1.28， = 0.0809）。对于 MRI 活动，两组之间未发现显著差异。治疗组与 CDP 相关的危险因素是男性和多发性硬化症病程。治疗组的 IIR 为每 100 人年 6.67（95%CI 3.12-14.25），未治疗组为 2.67（95%CI 0.80-8.86）。
讨论
接受抗 CD20 治疗和未接受治疗的 PPMS 患者首次 CDP 的时间无差异。尽管我们的研究是回顾性的，主要纳入了接受利妥昔单抗治疗的患者，但我们的结果表明，应该不断评估所有可用数据，以确定 PPMS 患者的最佳风险/获益比。
证据分类
这项研究提供了 III 级证据，表明抗 CD20 治疗未经治疗的 PPMS 患者在延迟首次 CDP 方面并不优于不治疗。
Zotero 插件