From the CORe (I.R., C.M., T.K.), Department of Medicine, University of Melbourne; Melbourne MS Centre (I.R., K.B., C.M., T.K.), Department of Neurology, Royal Melbourne Hospital, Australia; Rennes University (E.L.), EHESP, REPERES EA 7449; Univ Rennes (E.L.), CHU Rennes, Inserm, CIC 1414 (Centre d'Investigation Clinique de Rennes); Université de Lyon (R.C.), Université Claude Bernard Lyon 1; Hospices Civils de Lyon (R.C.), Service de Neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Bron; Observatoire Français de la Sclérose en Plaques (R.C.), Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292; EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis (R.C.), state-approved foundation, Bron, France; Department of Neurology and Center of Clinical Neuroscience (D.H., E.H.), First Faculty of Medicine, Charles University; General University Hospital (D.H., E.H.), Prague, Czech Republic; Hospital Universitario Virgen Macarena (G.I., S.E.M.), Sevilla, Spain; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia; Multiple Sclerosis Center (F.P.), University of Catania, Italy; Centre hospitalier universitaire de Rennes (G.E.), Hôpital Pontchaillou, Service de neurologie, CIC1414 INSERM; Nancy University Hospital (M.D.), Department of Neurology; Université de Lorraine (M.D.), APEMAC, Nancy, France; Aix Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, France; Dokuz Eylul University (S.O.), Konak/Izmir, Turkey; Department of Neurosciences, Psychology, Drugs and Child Health Area (NEUROFARBA) (M.P.A.), Section Neurosciences, University of Florence, Italy; CHU Clermont-Ferrand (P.C.), Department of Neurology; Université Clermont Auvergne (P.C.), Inserm, Neuro-Dol, Clermont-Ferrand, France; CISSS Chaudière-Appalache (P.G.), Lévis, Canada; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology (K.B., O.S., H.B.), Box Hill Hospital, Monash University; The Alfred Hospital (O.S.), Melbourne, Australia; CHU de Toulouse (J.C.), Hôpital Pierre-Paul Riquet, Department of Neurology, CRC-SEP, Toulouse Cedex 9, France; Department of Neurology (O.G.), Zuyderland Medical Center, Sittard-Geleen, the Netherlands; Neuro Rive-Sud (F.G.), Quebec, Canada; School of Medicine and Public Health (J.L.-S.), University Newcastle; Department of Neurology (J.L.-S.), John Hunter Hospital, Hunter New England Health, Newcastle; Central Clinical School (H.B.), Monash University; Department of Neurology (H.B.), The Alfred Hospital, Melbourne, Australia; Service de neurologie (S.V.), sclérose en plaques, pathologies de la myéline et neuro-inflammation; Hôpital Neurologique Pierre Wertheimer (S.V.), Hospices Civils de Lyon, Lyon/Bron; France Centre des Neurosciences de Lyon (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292; and Université Claude Bernard Lyon 1 (S.V.), Faculté de médecine Lyon Est, France.
Neurology. 2021 Aug 31;97(9):e869-e880. doi: 10.1212/WNL.0000000000012354. Epub 2021 Jun 30.
To compare the clinical effectiveness of high- and low-efficacy treatments in patients with recently active and inactive secondary progressive multiple sclerosis (SPMS) after accounting for therapeutic lag.
Patients treated with high-efficacy (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine, fingolimod) or low-efficacy (interferon beta, glatiramer acetate, teriflunomide) therapies after SPMS onset were selected from MSBase and Observatoire Français de la Sclérose en Plaques (OFSEP), 2 large observational cohorts. Therapeutic lag was estimated for each patient from their demographic and clinical characteristics. Propensity score was used to match patients treated with high- and low-efficacy therapies. Outcomes after the period of therapeutic lag was disregarded were compared in paired, pairwise-censored analyses.
One thousand patients were included in the primary analysis. Patients with active SPMS treated with high-efficacy therapy experienced less frequent relapses than those on low-efficacy therapy (hazard ratio [HR] 0.7, = 0.006). In patients with inactive SPMS, there was no evidence for a difference in relapse frequency between groups (HR 0.8, = 0.39). No evidence for a difference in the risk of disability progression was observed.
In treated patients with SPMS, high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active but not those with inactive SPMS. However, more potent therapies do not offer an advantage in reducing disability progression in this patient group.
This study provides Class III evidence that high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active SPMS, although we did not find a difference in disability progression between patients treated with high- and low-efficacy therapy.
在考虑治疗延迟后，比较近期活跃和不活跃的继发进展型多发性硬化症（SPMS）患者中高疗效和低疗效治疗的临床疗效。
从 MSBase 和 Observatoire Français de la Sclérose en Plaques（OFSEP）这两个大型观察性队列中选择 SPMS 发病后接受高疗效（那他珠单抗、阿仑单抗、米托蒽醌、奥瑞珠单抗、利妥昔单抗、克拉屈滨、芬戈莫德）或低疗效（干扰素β、聚乙二醇干扰素β-1a、特立氟胺）治疗的患者。根据患者的人口统计学和临床特征估计每位患者的治疗延迟。使用倾向评分匹配接受高和低疗效治疗的患者。在配对、成对删失分析中比较治疗延迟期后忽略的结局。
共有 1000 名患者纳入主要分析。接受高疗效治疗的活跃 SPMS 患者比接受低疗效治疗的患者发生复发的频率更低（风险比 [HR] 0.7， = 0.006）。在不活跃 SPMS 患者中，两组之间复发频率无差异（HR 0.8， = 0.39）。未发现残疾进展风险存在差异。
在 SPMS 治疗患者中，与低疗效治疗相比，高疗效治疗可降低活跃 SPMS 患者的复发风险，但在该患者人群中，更有效的治疗并不能降低残疾进展的风险。
这项研究提供了 III 级证据，表明与低疗效治疗相比，高疗效治疗可降低活跃 SPMS 患者的复发风险，但我们未发现接受高和低疗效治疗的患者在残疾进展方面存在差异。
