Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis
Authors: Kalincik Tomas , Sharmin Sifat , Roos Izanne , Freedman Mark S. , Atkins Harold , Burman Joachim , Massey Jennifer , Sutton Ian , Withers Barbara , Macdonell Richard , Grigg Andrew , Torkildsen Øivind , Bo Lars , Lehmann Anne Kristine , Havrdova Eva Kubala , Krasulova Eva , Trněný Marek , Kozak Tomas , van der Walt Anneke , Butzkueven Helmut , McCombe Pamela , Skibina Olga , Lechner-Scott Jeannette , Willekens Barbara , Cartechini Elisabetta , Ozakbas Serkan , Alroughani Raed , Kuhle Jens , Patti Francesco , Duquette Pierre , Lugaresi Alessandra , Khoury Samia J. , Slee Mark , Turkoglu Recai , Hodgkinson Suzanne , John Nevin , Maimone Davide , Sa Maria Jose , van Pesch Vincent , Gerlach Oliver , Laureys Guy , Van Hijfte Liesbeth , Karabudak Rana , Spitaleri Daniele , Csepany Tunde , Gouider Riadh , Castillo-Triviño Tamara , Taylor Bruce , Sharrack Basil , Snowden John A. ,   MSBase Study Group Collaborators,   MSBase Study Group Authors, Horakova Dana , Buzzard Katherine , Terzi Murat , Prat Alexandre , Girard Marc , Grammond Pierre , Barnett Michael , Stewart Grace , Onofrj Marco , Izquierdo Guillermo , Eichau Sara , Grand'Maison Francois , Prevost Julie , Van Wijmeersch Bart , Amato Maria Pia , Shaygannejad Vahid , Boz Cavit , Bolaños Ricardo Fernandez , Soysal Aysun , Ramo-Tello Cristina , Solaro Claudio , Gobbi Claudio , Cabrera-Gomez Jose Antonio , Roullet Etienne , Zwanikken Cees , Den braber-Moerland Leontien , Deri Norma , Saladino Maria Laura , Cristiano Edgardo , Rojas Juan Ignacio , Vrech Carlos , Shaw Cameron , Shuey Neil , Boggild Mike , Tan Ik Lin , Hardy Todd , Decoo Danny , Moore Fraser , Oh Jiwon , Lalive Patrice , Ampapa Radek , Petersen Thor , Oreja-Guevara Celia , Perez Sempere Angel , Dominguez Jose Andres , Besora Sarah , Hughes Stella , Gray Orla , Grigoriadis Nikolaos , Piroska Imre , Rozsa Csilla , Kasa Krisztian , Simo Magdolna , Kovacs Krisztina , Sas Attila , Dobos Eniko , Rajda Cecilia , McGuigan Chris , Mason Deborah , Schepel Jan , Alkhaboori Jabir , Rio Maria Edite , Mihaela Simu , Al-Harbi Talal , Altintas Ayse , Kister Ilya , Marriott Mark , Kilpatrick Trevor , King John , Nguyen Ai-Lan , Dwyer Chris , Monif Mastura , Roos Izanne , Taylor Lisa , Diamanti Matteo , Chisari Clara , Toscano Simona , Salvatore Lo Fermo , Larochelle Catherine , De Luca Giovanna , Di Tommaso Valeria , Travaglini Daniela , Pietrolongo Erika , di Ioia Maria , Farina Deborah , Mancinelli Luca , Hupperts Raymond , Olascoaga Javier , Saiz Albert , Zivadinov Robert , Benedict Ralph , Verheul Freek , Fabis-Pedrini Marzena , Mrabet Saloua , Garber Justin , Sanchez-Menoyo Jose Luis , Aguera-Morales Eduardo , Blanco Yolanda , Al-Asmi Abdullah , Weinstock-Guttman Bianca , Fragoso Yara , de Gans Koen , Kermode Allan 
Published: May 2023

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.