Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis

被引：21

作者：

Kalincik, Tomas ^{[1
,2
]}

Sharmin, Sifat ^{[1
,2
]}

Roos, Izanne ^{[1
,2
]}

Freedman, Mark S. ^{[3
]}

Atkins, Harold ^{[4
]}

Burman, Joachim ^{[5
]}

Massey, Jennifer ^{[6
,7
]}

Sutton, Ian ^{[6
,8
]}

Withers, Barbara ^{[7
,9
]}

Macdonell, Richard ^{[10
,11
]}

Grigg, Andrew ^{[11
,12
]}

Torkildsen, Oivind ^{[13
]}

Bo, Lars ^{[13
]}

Lehmann, Anne Kristine ^{[14
]}

Havrdova, Eva Kubala ^{[15
,16
]}

Krasulova, Eva ^{[15
,16
]}

Trneny, Marek ^{[16
,17
]}

Kozak, Tomas ^{[18
,19
]}

van der Walt, Anneke ^{[20
,21
]}

Butzkueven, Helmut ^{[20
,21
]}

McCombe, Pamela ^{[22
,23
]}

Skibina, Olga ^{[20
,24
,25
]}

Lechner-Scott, Jeannette ^{[26
,27
]}

Willekens, Barbara ^{[28
,29
]}

Cartechini, Elisabetta ^{[30
]}

Ozakbas, Serkan ^{[31
]}

Alroughani, Raed ^{[32
]}

Kuhle, Jens ^{[33
,34
,35
]}

Patti, Francesco ^{[36
,37
]}

Duquette, Pierre ^{[38
,39
]}

Lugaresi, Alessandra ^{[40
,41
]}

Khoury, Samia J. ^{[42
]}

Slee, Mark ^{[43
]}

Turkoglu, Recai ^{[44
]}

Hodgkinson, Suzanne ^{[45
]}

John, Nevin ^{[46
,47
]}

Maimone, Davide ^{[48
]}

Sa, Maria Jose ^{[49
]}

van Pesch, Vincent ^{[50
,51
]}

Gerlach, Oliver ^{[52
,53
]}

Laureys, Guy ^{[54
]}

Van Hijfte, Liesbeth ^{[54
]}

Karabudak, Rana ^{[55
]}

Spitaleri, Daniele ^{[56
]}

Csepany, Tunde ^{[57
]}

Gouider, Riadh ^{[58
,59
]}

Castillo-Trivino, Tamara ^{[60
]}

Taylor, Bruce ^{[61
,62
]}

Sharrack, Basil ^{[63
]}

Snowden, John A. ^{[64
]}

机构：

[1] Royal Melbourne Hosp, Dept Neurol, Ctr Neuroimmunol, Melbourne, Vic, Australia

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

[3] Univ Ottawa, Ottawa Hosp Res Inst, Dept Med, Ottawa, ON, Canada

[4] Univ Ottawa, Ottawa Hosp Res Inst, Ottawa, ON, Canada

[5] Uppsala Univ, Neurol, Dept Med Sci, Uppsala, Sweden

[6] St Vincents Hosp Sydney, Dept Neurol, Sydney, NSW, Australia

[7] Univ New South Wales, St Vincents Clin Sch, Sydney, NSW, Australia

[8] Univ Sydney, Sydney, NSW, Australia

[9] St Vincents Hosp Sydney, Dept Haematol, Sydney, NSW, Australia

[10] Austin Hlth, Dept Neurol, Melbourne, Vic, Australia

[11] Univ Melbourne, Melbourne, Vic, Australia

[12] Austin Hlth, Dept Haematol, Melbourne, Vic, Australia

[13] Haukeland Hosp, Dept Neurol, Bergen, Norway

[14] Haukeland Hosp, Dept Haematol, Bergen, Norway

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

[16] Gen Univ Hosp, Prague, Czech Republic

[17] Charles Univ Prague, Fac Med 1, Dept Haematol, Prague, Czech Republic

[18] Charles Univ Prague, Dept Haematol, Fac Med 3, Prague, Czech Republic

[19] Univ Hosp Kralovske Vinohrady, Prague, Czech Republic

[20] Alfred Hosp, Dept Neurol, Melbourne, Vic, Australia

[21] Monash Univ, Cent Clin Sch, Melbourne, Vic, Australia

[22] Univ Queensland, Brisbane, Qld, Australia

[23] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia

[24] Box Hill Hosp, Dept Neurol, Melbourne, Vic, Australia

[25] Monash Univ, Melbourne, Vic, Australia

[26] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW, Australia

[27] Hunter New England Hlth, Dept Neurol, John Hunter Hosp, Newcastle, NSW, Australia

[28] Antwerp Univ Hosp, Dept Neurol, Edegem, Belgium

[29] Univ Antwerp, Translat Neurosci Res Grp, Fac Med & Hlth Sci, Antwerp, Belgium

[30] Azienda Sanit Unica Reg Marche AV3, UOC Neurol, Macerata, Italy

[31] Dokuz Eylul Univ, Izmir, Turkiye

[32] Amiri Hosp, Div Neurol, Dept Med, Sharq, Kuwait

[33] Univ Hosp, Neurol Clin & Policlin, Dept Med, Basel, Switzerland

[34] Univ Hosp, Neurol Clin & Policlin, Dept Clin Res, Basel, Switzerland

[35] Univ Basel, Basel, Switzerland

[36] GF Ingrassia, Dept Med & Surg Sci & Adv Technol, Catania, Italy

[37] Univ Catania, Multiple Sclerosis Ctr, Catania, Italy

[38] CHUM MS Ctr, Montreal, PQ, Canada

[39] Univ Montreal, Montreal, PQ, Canada

[40] IRCCS Ist Sci Neurol Bologna, Bologna, Italy

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

[42] Amer Univ Beirut, Med Ctr, Nehme & Therese Tohme Multiple Sclerosis Ctr, Beirut, Lebanon

[43] Flinders Univ S Australia, Adelaide, SA, Australia

[44] Haydarpasa Numune Training & Res Hosp, Istanbul, Turkiye

[45] Liverpool Hosp, Sydney, NSW, Australia

[46] Monash Med Ctr, Melbourne, Vic, Australia

[47] Monash Univ, Dept Med, Sch Clin Sci, Melbourne, Vic, Australia

[48] Garibaldi Hosp, Catania, Italy

[49] Ctr Hosp Univ Sao Joao, Dept Neurol, Porto, Portugal

[50] Clin Univ St Luc, Brussels, Belgium

来源：

JAMA NEUROLOGY | 2023年 / 80卷 / 07期

基金：

英国医学研究理事会;

关键词：

THERAPY; IMMUNOABLATION; DISABILITY; REVISIONS; TRIAL;

D O I：

10.1001/jamaneurol.2023.1184

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Importance Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS).Objective To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials.Design, Setting, and Participants This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics.Exposure AHSCT vs fingolimod, natalizumab, or ocrelizumab.Main outcomes Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement.Results Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%).Conclusion In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.

引用

页码：702 / 713

页数：12

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