TY - JOUR
T1 - Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis
AU - Kalincik, Tomas
AU - Sharmin, Sifat
AU - Roos, Izanne
AU - Freedman, Mark S.
AU - Atkins, Harold
AU - Burman, Joachim
AU - Massey, Jennifer
AU - Sutton, Ian
AU - Withers, Barbara
AU - MacDonell, Richard
AU - Grigg, Andrew
AU - Torkildsen, Øivind
AU - Bo, Lars
AU - Lehmann, Anne Kristine
AU - Havrdova, Eva Kubala
AU - Krasulova, Eva
AU - Trněný, Marek
AU - Kozak, Tomas
AU - Van Der Walt, Anneke
AU - Butzkueven, Helmut
AU - McCombe, Pamela
AU - Skibina, Olga
AU - Lechner-Scott, Jeannette
AU - Willekens, Barbara
AU - Cartechini, Elisabetta
AU - Ozakbas, Serkan
AU - Alroughani, Raed
AU - Kuhle, Jens
AU - Patti, Francesco
AU - Duquette, Pierre
AU - Lugaresi, Alessandra
AU - Khoury, Samia J.
AU - Slee, Mark
AU - Turkoglu, Recai
AU - Hodgkinson, Suzanne
AU - John, Nevin
AU - Maimone, Davide
AU - Sa, Maria Jose
AU - Van Pesch, Vincent
AU - Gerlach, Oliver
AU - Laureys, Guy
AU - Van Hijfte, Liesbeth
AU - Karabudak, Rana
AU - Spitaleri, Daniele
AU - Csepany, Tunde
AU - Gouider, Riadh
AU - Castillo-Triviño, Tamara
AU - Taylor, Bruce
AU - Sharrack, Basil
AU - Snowden, John A.
AU - MSBase Study Group Authors; for the MSBase Study Group Collaborators
AU - Mrabet, Saloua
AU - Garber, Justin
AU - Sanchez-Menoyo, Jose Luis
AU - Aguera-Morales, Eduardo
AU - Blanco, Yolanda
AU - Al-Asmi, Abdullah
AU - Weinstock-Guttman, Bianca
AU - Fragoso, Yara
AU - De Gans, Koen
AU - Kermode, Allan
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
KW - multiple sclerosis (MS)
KW - Autologous hematopoietic stem cell transplant (AHSCT)
KW - fingolimod
KW - natalizumab
KW - relapse rates
KW - Clinical study
UR - http://www.scopus.com/inward/record.url?scp=85164541334&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1140766
UR - http://purl.org/au-research/grants/NHMRC/1129189
U2 - 10.1001/jamaneurol.2023.1184
DO - 10.1001/jamaneurol.2023.1184
M3 - Article
C2 - 37437240
AN - SCOPUS:85164541334
SN - 2168-6149
VL - 80
SP - 702
EP - 713
JO - JAMA Neurology
JF - JAMA Neurology
IS - 7
ER -