Browsing by Author "Atkins, Harold"

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Effectiveness of Autologous Haematopoietic Stem Cell Transplant in Comparison With Anti-CD20 Therapies in Relapsing-Remitting Multiple Sclerosis
(Sage Publications Ltd, 2025) Kalincik, Tomas; Sharmin, Sifat; Roos, Izanne; Freedman, Mark S.; Atkins, Harold; Massey, Jennifer; Snowden, John
Effectiveness of Autologous Haematopoietic Stem Cell Transplantation in Comparison With Immune-Reconstitution Therapies in Relapsing-Remitting MS
(Sage Publications Ltd, 2024) Kalincik, Tomas; Sharmin, Sifat; Roos, Izanne; Freedman, Mark S.; Atkins, Harold; Massey, Jennifer; Snowden, John
Haematopoietic Stem Cell Transplant versus Immune-Reconstitution Therapy in Relapsing Multiple Sclerosis
(Oxford Univ Press, 2026) Atkins, Harold; Snowden, John A.; Kalincik, Tomas; Sharmin, Sifat; Roos, Izanne; Freedman, Mark S.; Massey, Jennifer
In the treatment of relapsing-remitting multiple sclerosis, autologous haematopoietic stem cell transplant (AHSCT) and immune-reconstitution therapies show several similarities. These treatment strategies have not yet been compared head-to-head. This study emulated pairwise trials of comparative effectiveness of stem cell transplant versus immune-reconstitution therapies cladribine and alemtuzumab. This cohort/registry study of comparative treatment effectiveness included data from seven specialist multiple sclerosis centres with AHSCT programmes (RESCUE-MS) and international MSBase registry during 2006-2023. The study included patients with relapsing-remitting multiple sclerosis treated with AHSCT, cladribine or alemtuzumab, with a minimum of 2-months follow-up before commencing study therapy and >= 2 disability assessments after commencing the study therapy. Patients were matched on a propensity score derived from their clinical and demographic characteristics. The matched groups were compared according to annualized relapse rates, freedom from relapses and 6-month confirmed disability worsening and improvement (measured with the Expanded Disability Status Scale). The matching of 143 (stem cell) to 283 cladribine-treated patients and 134 (stem cell) to 562 alemtuzumab-treated patients reduced the measured differences between the groups by 98% and 96%, respectively. The matched patients had high mean disease activity (>0.8 relapses in the prior 2 years), mean Expanded Disability Status Scale scores of 3-4, and were followed-up for a mean of 3.8-3.9 (stem cell), 1.9 (cladribine) or 4.5 years (alemtuzumab). Compared with cladribine, stem cell transplant was associated with a lower risk of relapse [mean annualized relapse rate +/- standard deviation (SD): 0.05 +/- 0.28 versus 0.16 +/- 0.39, respectively; hazard ratio: 0.24; 95% confidence interval (CI): 0.15-0.41], similar risk of disability worsening (hazard ratio: 0.70; 95% CI: 0.34-1.43) and higher probability of disability improvement (hazard ratio: 2.19; 95% CI: 1.31-3.66). Compared with alemtuzumab, stem cell transplant was associated with a lower risk of relapses (mean annualized relapse rate +/- SD: 0.04 +/- 0.23 versus 0.09 +/- 0.21, respectively; hazard ratio: 0.52; 95% CI: 0.29-0.93), similar risk of disability worsening (hazard ratio: 0.95; 95% CI: 0.53-1.72) and higher probability of disability improvement (hazard ratio: 2.03; 95% CI: 1.23-3.34). Thirty-four per cent of patients treated with stem cell transplant experienced delayed complications, mainly infections. No treatment-associated deaths were reported. Among patients with active relapsing-remitting multiple sclerosis and moderate disability, AHSCT is superior to cladribine and alemtuzumab at suppressing relapses and enabling recovery of neurological function. The high effectiveness of stem cell transplant is likely attributable to a complex interplay between immune suppression and reconstitution.