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

Abstract

ImportanceAutologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS).ObjectiveTo compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials.Design, Setting, and ParticipantsThis 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.ExposureAHSCT vs fingolimod, natalizumab, or ocrelizumab.Main outcomesPairwise-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.ResultsOf 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%).ConclusionIn 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.

Cost and effectiveness of autologous haematopoietic stem cell transplantation and high-efficacy disease-modifying therapies in relapsing–remitting multiple sclerosis

“…In this respect, indirect comparisons suggest that AHSCT may induce rates of NEDA remarkably higher than DMTs [ 2 , 29 ]. Even if head-to-head comparisons with HE-DMTs are lacking, possible superior effectiveness of AHSCT was suggested over natalizumab [ 2 , 30 ], fingolimod [ 30 ], and alemtuzumab [ 31 ]. Indeed, disease burden and accumulated disability are usually higher in the published experiences on AHSCT than in patients included in Registration Studies, therefore providing an unfavourable outcome scenario in AHSCT.…”

“…Based on these observations, AHSCT may represent an optimal front-loading strategy of costs in RR-MS, especially in cases bearing poor prognostic factors. Besides lower treatment-cost to prevent long-term disability accrual (almost half of the mean cost for HE-DMTs), AHSCT could offer further advantages as it may induce higher rates of disability improvement compared to HE-DMTs [ 30 ]. The latter effect may contribute to additional savings of the indirect costs related to loss of working abilities and social care expenditure: compared to mild disability, total costs for moderate and severe disability were recently estimated as 1.4–2.3-fold and 1.8–2.9-fold higher, respectively [ 37 ].…”

Haematopoietic Stem Cell Transplantation for the Treatment of Multiple Sclerosis: Recent Advances

“…The comparative effectiveness of AHSCT vs. fingolimod, natalizumab and ocrelizumab in RRMS was explored in 167 AHSCT-treated patients who were propensity score matched to controls exposed to one of these DMTs, selected from the MSBase Registry [ 37 ]. Over 5 years, AHSCT was associated with a lower risk of relapses and a higher chance of disability improvement compared with fingolimod and natalizumab, with a similar effect on disability worsening.…”

Stem Cell Transplantation for Multiple Sclerosis: A 2023 Review of Published Studies

“…Kalincik et al recently conducted a multicenter observational comparative study evaluating the efficacy of HSCT in comparison to other DMTs [ 12 ]. The study has demonstrated the superiority of HSCT over fingolimod in blunting relapse rates.…”