Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry

被引：16

作者：

Butzkueven, Helmut ^{[1
]}

Spelman, Tim ^{[2
,3
,4
]}

Horakova, Dana ^{[5
,6
]}

Hughes, Stella ^{[7
,8
]}

Solaro, Claudio ^{[9
]}

Izquierdo, Guillermo ^{[10
]}

Kubala Havrdova, Eva ^{[11
,12
,13
]}

Grand'Maison, Francois ^{[14
]}

Prat, Alexandre ^{[15
,16
]}

Girard, Marc ^{[15
,16
]}

Hupperts, Raymond ^{[17
]}

Onofrj, Marco ^{[18
]}

Lugaresi, Alessandra ^{[19
,20
]}

Taylor, Bruce ^{[21
]}

Giovannoni, Gavin ^{[22
]}

Kappos, Ludwig ^{[23
,24
,25
]}

Hauser, Stephen L. ^{[26
]}

Montalban, Xavier ^{[27
]}

Craveiro, Licinio ^{[28
]}

Freitas, Rita ^{[28
]}

Model, Fabian ^{[28
]}

Overell, James ^{[28
]}

Muros-Le Rouzic, Erwan ^{[28
]}

Sauter, Annette ^{[28
]}

Wang, Qing ^{[28
]}

Wormser, David ^{[28
]}

Wolinsky, Jerry S. ^{[29
]}

机构：

[1] Monash Univ, Cent Clin Sch, Dept Neurosci, Melbourne, Vic, Australia

[2] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Melbourne, Vic, Australia

[3] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Melbourne, Vic, Australia

[4] Charles Univ Prague, Fac Med 1, Dept Neurol, Prague, Czech Republic

[5] Charles Univ Prague, Fac Med 1, Ctr Clin Neurosci, Prague, Czech Republic

[6] Gen Univ Hosp, Prague, Czech Republic

[7] Craigavon Area Hosp, Dept Neurol, Craigavon, North Ireland

[8] Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland

[9] CRRF Mons Luigi Novarese, Moncrivello, VC, Italy

[10] Vithas Nisa Hosp, Seville, Spain

[11] Gen Univ Hosp, Dept Neurol, Prague, Czech Republic

[12] Gen Univ Hosp, Ctr Clin Neurosci, Prague, Czech Republic

[13] Charles Univ Prague, Prague, Czech Republic

[14] Neuro Rive Sud, Quebec City, PQ, Canada

[15] CHUM, Montreal, PQ, Canada

[16] Univ Montreal, Montreal, PQ, Canada

[17] Zuyderland Ziekenhuis, Sittard, Netherlands

[18] Univ G dAnnunzio, Chieti, Italy

[19] IRCCS Ist Sci Neurol Bologna, UOSI Riabil Sclerosi Multipla, Bologna, Italy

[20] Univ Bologna, Dipartimento Sci Biomed & Neuromotorie, Bologna, Italy

[21] Royal Hobart Hosp, Hobart, Tas, Australia

[22] Queen Mary Univ London, London, England

[23] Univ Hosp Basel, Res Ctr Clin Neuroimmunol & Neurosci, Basel, Switzerland

[24] Univ Hosp Basel, MS Ctr, Basel, Switzerland

[25] Univ Basel, Basel, Switzerland

[26] Univ Calif San Francisco, San Francisco, CA 94143 USA

[27] Hosp Univ Vall dHebron, Ctr Esclerosi Multiple Catalunya Cemcat, Dept Neurol Neuroimmunol, Barcelona, Spain

[28] F Hoffmann La Roche Ltd, Basel, Switzerland

[29] Univ Texas Hlth Sci Ctr Houston, UTHlth, McGovern Med Sch, Houston, TX 77030 USA

来源：

EUROPEAN JOURNAL OF NEUROLOGY | 2022年 / 29卷 / 04期

关键词：

disease progression; ocrelizumab; primary progressive multiple sclerosis; wheelchair; OCRELIZUMAB; PLACEBO; CD20;

D O I：

10.1111/ene.14824

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and purpose Reaching Expanded Disability Status Scale (EDSS) >= 7.0 represents the requirement for a wheelchair. Here we (i) assess the effect of ocrelizumab on time to EDSS >= 7.0 over the ORATORIO (NCT01194570) double-blind and extended controlled periods (DBP+ECP), (ii) quantify likely long-term benefits by extrapolating results, and (iii) assess the plausibility of extrapolations using an independent real-world cohort (MSBase registry; ACTRN12605000455662). Methods Post hoc analyses assessing time to 24-week confirmed EDSS >= 7.0 in two cohorts of patients with primary progressive multiple sclerosis (baseline EDSS 3.0-6.5) were investigated in ORATORIO and MSBase. Results In the ORATORIO DBP+ECP, ocrelizumab reduced the risk of 24-week confirmed EDSS >= 7.0 (hazard ratio = 0.54, 95% confidence interval [CI]: 0.31-0.92; p = 0.022). Extrapolated median time to 24-week confirmed EDSS >= 7.0 was 12.1 and 19.2 years for placebo and ocrelizumab, respectively (7.1-year delay [95% CI: -4.3 to 18.4]). In MSBase, the median time to 24-week confirmed EDSS >= 7.0 was 12.4 years. Conclusions Compared with placebo, ocrelizumab significantly delayed time to 24-week confirmed wheelchair requirement in ORATORIO. The plausibility of the extrapolated median time to reach this milestone in the placebo group was supported by observed real-world data from MSBase. Extrapolated benefits for ocrelizumab over placebo could represent a truly meaningful delay in loss of ambulation and independence.

引用

页码：1082 / 1090

页数：9

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