Browsing by Author "Roos, Izanne"

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Cladribine as an Exit Strategy in People with MS Over the Age of 50
(Sage Publications Ltd, 2025) Roos, Izanne; Sharmin, Sifat; Mueller, Jannis; Horakova, Dana; Havrdova, Eva; Ozakbas, Serkan; Kalincik, Tomas
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.
Citation - Scopus: 1
Persistent Progression Independent of Relapse Activity in Multiple Sclerosis
(Oxford Univ Press, 2025) Zhu, Chao; Zhou, Zhen; Kalincik, Tomas; Roos, Izanne; Buzzard, Katherine; Skibina, Olga; Butzkueven, Helmut
Patients with relapsing-remitting multiple sclerosis (RRMS) may experience disability progression independent of relapse activity (PIRA), which can be an early sign of secondary progressive MS (SPMS). We defined persistent PIRA as ongoing sustained disability over the entire available follow-up period. However, PIRA events can regress over time. Identifying factors that predict PIRA persistence is of great interest as they can refine the definition of RRMS to SPMS transition. Equally, factors associated with the non-persistence of PIRA have potential treatment implications for patients suffering from a PIRA event. We conducted a study to examine risk factors for PIRA persistence and risk differences in long-term disability progression between persistent and non-persistent PIRA. In this cohort study, we included only patients who had already experienced a PIRA event and investigated the persistence of disability progression following their first PIRA event. Therefore, PIRA occurrence time was set as the baseline. Data were collected from the MSBase registry between April 1995 and January 2024, with a median follow-up of 8.7 years. The primary outcome was time to 6-month confirmed non-persistence of PIRA. Secondary outcomes comprised time to 6-month confirmed Expanded Disability Status Scale (EDSS) 6 and time to SPMS. A stratified Cox regression model was used to identify risk factors associated with non-persistent PIRA. We then matched persistent PIRA patients with non-persistent PIRA patients in a 1:1 ratio using propensity scores, and compared their risk of reaching EDSS 6 using the Cox regression model. We re-matched patients with complete Kurtzke Functional Systems Scores to compare their risks of reaching SPMS. We included 4713 RRMS patients with PIRA, of whom around one-third experienced a post-PIRA disability improvement, over a relatively long period (median of 2.6 years to improvement). Use of high-efficacy disease-modifying therapies (DMT) at baseline [hazard ratio, 1.22; 95% confidence interval, (1.08-1.38); P = 0.0015], lower baseline EDSS [hazard ratio, 0.73 (0.69-0.78); P < 0.0001] and younger age [per 10 years; hazard ratio, 0.84 (0.80-0.89); P < 0.0001] were associated with non-persistent PIRA. Patients with non-persistent PIRA had a hazard ratio of 0.19 [95% confidence interval, (0.15-0.25); P < 0.0001] for reaching EDSS 6 and 0.18 [(0.11-0.29); P < 0.0001] for reaching SPMS compared to patients with persistent PIRA. PIRA events slowly regress in one-third of patients. Patients with persistent PIRA had a substantially higher risk of reaching EDSS 6 and SPMS than those with non-persistent PIRA. Younger age, lower baseline EDSS, and use of high-efficacy DMT during PIRA events were associated with PIRA regression.
Preserving Neurological Function in Patients at High Risk and Low Risk of Aggressive MM
(Sage Publications Ltd, 2024) Roos, Izanne; Sharmin, Sifat; Ozakbas, Serkan; Alroughani, Raed; Ayuso, Guillermo Izquierdo; Madueno, Sara Eichau; Kalincik, Tomas
Real-World Effectiveness of Ocrelizumab in Multiple Sclerosis: A Multi-Registry Observational Cohort Study
(Sage Publications Ltd, 2025) Roos, Izanne; Sharmin, Sifat; Horakova, Dana; Ozakbas, Serkan; Libertinova, Jana; Boz, Cavit; Kalincik, Tomas
Treatment Strategies After Cell-Trafficking Agents in MS Patients Older Than 50 Years
(Sage Publications Ltd, 2025) Muller, Jannis; Benkert, Pascal; Horakova, Dana; Havrdova, Eva; Buzzard, Katherine; Skibina, Olga; Roos, Izanne