Browsing by Author "Sharmin, Sifat"

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Bayesian Network to Generate Representative Longitudinal Data in Multiple Sclerosis
(Sage Publications Ltd, 2025) Qiang, Zhe; Iqbal, Hassam; Sharmin, Sifat; Ozakbas, Serkan; Zakaria, Magd Fouad; Etemadifar, Masoud; Kalincik, Tomas
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
Machine Learning-Generated Longitudinal Synthetic International Data in Multiple Sclerosis
(Sage Publications Ltd, 2025) Iqbal, Hassam; Qiang, Zhe; Sharmin, Sifat; Ball, Gareth; Brankovic, Aida; Horakova, Dana; Kalincik, Tomas
Managing Reactivation of Multiple Sclerosis During Treatment with Natalizumab
(Sage Publications Ltd, 2026) Lizak, Nathaniel; Sharmin, Sifat; Horakova, Dana; Havrdova, Eva Kubala; Eichau, Sara; Van Der Walt, Anneke; Kalincik, Tomas
Background: Following natalizumab failure, it is unknown whether switching to alternative high-efficacy therapies offers superior effectiveness over continuing natalizumab. Objective: To compare different treatment strategies following natalizumab failure. Methods: Patients suffering a relapse during natalizumab treatment with adequate follow-up were identified from the MSBase registry. Following natalizumab failure, natalizumab continuation was compared to switching to anti-CD20 therapies/alemtuzumab/lower-efficacy therapies and treatment discontinuation. The primary outcome was the risk of further relapses. Secondary outcomes included risk of subsequent magnetic resonance imaging (MRI) activity, confirmed disability worsening and disease-activity-free survival. Multivariable proportional hazards models compared outcomes during time-varying therapy exposures. Four sensitivity analyses were conducted with varied inclusion criteria and treatment failure definitions. Results: Of 1553 patients experiencing a relapse during natalizumab treatment, 1037 met the inclusion criteria. Following natalizumab failure, switch to anti-CD20 therapy was associated with a lower relapse risk (heart rate (HR) = 0.48, 95% confidence interval (CI) = 0.27-0.84) compared to continuing natalizumab; no differences were observed in MRI or disability outcomes. Treatment de-escalation or cessation was associated with increased relapse risk (HR = 1.46, 95% CI = 1.15-1.85; HR = 2.08, 95% CI = 1.22-3.55, respectively). We did not find evidence of a difference for switching to alemtuzumab. Sensitivity analyses replicated primary findings. Conclusion: This exploratory study indicates that switching to anti-CD20 therapies following natalizumab failure is associated with a >50% reduction in relapse risk. No differences were seen in secondary outcomes, despite consistent trends. Clinicians may consider anti-CD20 therapies following natalizumab failure, noting further research is needed to confirm differences in MRI and disability outcomes.
Citation - WoS: 5
Citation - Scopus: 7
Predictors of Relapse Risk and Treatment Response in Aqp4-Igg Positive and Seronegative Nmosd: a Multicentre Study
(Bmj Publishing Group, 2024) Siriratnam, Pakeeran; Sanfilippo, Paul; van der Walt, Anneke; Sharmin, Sifat; Foong, Yi Chao; Yeh, Wei Zhen; Zhu, Chao
Background Neuromyelitis optica spectrum disorder (NMOSD) can be categorised into aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative NMOSD remains less understood. This study aimed to evaluate the predictors of relapses and treatment responses in AQP4-IgG NMOSD and seronegative NMOSD. Methods This was a multicentre, international, retrospective cohort study using the MSBase registry. Recurrent relapse risk was assessed using an Andersen-Gill model and risk of first relapse was evaluated using a Cox proportional hazards model. Covariates that putatively influence relapse risk included demographic factors, clinical characteristics and immunosuppressive therapies; the latter was assessed as a time-varying covariate. Results A total of 398 patients (246 AQP4-IgG NMOSD and 152 seronegative NMOSD) were included. The AQP4-IgG NMOSD and seronegative NMOSD patients did not significantly differ by age at disease onset, ethnicity or annualised relapse rate. Both low-efficacy and high-efficacy immunosuppressive therapies were associated with significant reductions in recurrent relapse risk, with notably greater protection conferred by high-efficacy therapies in both AQP4-IgG NMOSD (HR 0.27, 95% CI 0.15 to 0.49, p<0.001) and seronegative NMOSD (HR 0.21, 95% CI 0.08 to 0.51, p<0.001). Longer disease duration (HR 0.97, 95% CI 0.95 to 0.99, p<0.001) and male sex (HR 0.52, 95% CI 0.34 to 0.84, p=0.007) were additional protective variables in reducing the recurrent relapse risk for the AQP4-IgG NMOSD group. Conclusion Although further studies are needed to improve our understanding of seronegative NMOSD, our findings underscore the importance of aggressive treatment with high-efficacy immunotherapies in both NMOSD subtypes, regardless of serostatus.
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
Citation - WoS: 10
Citation - Scopus: 9
Prevalence of Progression Independent of Relapse Activity and Relapse-Associated Worsening in Patients With AQP4-IgG-Positive NMOSD
(Lippincott Williams & Wilkins, 2024) Siriratnam, Pakeeran; Huda, Saif; van der Walt, Anneke; Sanfilippo, Paul G.; Sharmin, Sifat; Foong, Yi Chao; Monif, Mastura
ObjectivesIn aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), disability accrual is mostly attributed to relapses. This study aimed to assess the prevalence of progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in AQP4-IgG NMOSD.MethodsThis was a retrospective cohort study of patients with AQP4-IgG NMOSD enrolled in the MSBase international data registry. Patients required a minimum of 3 recorded Expanded Disability Status Scale (EDSS) scores: baseline, event, and a 6-month confirmation score. Presence and absence of relapses between the baseline and event EDSS scores determined RAW and PIRA, respectively. Descriptive statistics were used to present the results.ResultsA total of 181 patients followed for a median of 4.5 years (Q1 1.7, Q3 7.8) were included. Most patients were female (88.4%), and the median age at disease onset was 38.1 years. Overall, 4 patients (2.2%) developed 5 incidences of PIRA and 13 patients developed RAW (7.2%).DiscussionThis multicenter study highlights that PIRA is very rare in AQP4-IgG NMOSD. Limitations of this study include the sole focus of overall EDSS to measure disability, lack of requirement for a second EDSS score to confirm baseline EDSS, and the absence of magnetic resonance imaging information for all patients.
Citation - WoS: 1
Citation - Scopus: 1
Progression Independent of Relapse Activity and Relapse-Associated Worsening in Seronegative Nmosd: an International Cohort Study
(Springer Heidelberg, 2025) Siriratnam, Pakeeran; Huda, Saif; van der Walt, Anneke; Sanfilippo, Paul; Sharmin, Sifat; Foong, Yi Chao; Monif, Mastura
BackgroundPrevious studies have indicated that progression independent of relapse activity (PIRA) is uncommon in patients with aquaporin- 4 antibody-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD). However, the patterns of disability accumulation in seronegative NMOSD are unknown. This study aimed to evaluate the prevalence of PIRA and relapse-associated worsening (RAW) in seronegative NMOSD.MethodsWe conducted a retrospective, multicentre cohort study of seronegative NMOSD patients from the MSBase registry. Inclusion criteria required at least three recorded expanded disability status scale (EDSS) scores: baseline, progression, and 6 months confirmed disability progression (CDP). For those with 6-month CDP, the presence or absence of relapse between baseline and progression determined the classification as RAW or PIRA, respectively. Descriptive statistics were employed to present the data.ResultsThis study included 93 patients, with a median follow-up duration of 5.0 years (Q1 2.8, Q3 8.4). The cohort predominantly consisted of female patients (77.4%), with a median age of onset of 33.9 years (Q1 26.1, Q3 41.2). PIRA was observed in 1 case (1.1%), whilst RAW was documented in 7 cases (7.5%).ConclusionThis international cohort study confirms that CDP is uncommon in seronegative NMOSD. Given more than three quarters of CDP occur due to RAW, therapeutic strategies should focus primarily on preventing relapses.
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
A Standardised Definition of Progression Independent of Relapse Activity in Multiple Sclerosis
(Sage Publications Ltd, 2024) Mueller, Jannis; Sharmin, Sifat; Lorscheider, Johannes; Ozakbas, Serkan; Karabudak, Rana; Horakova, Dana; Kalincik, Tomas
Citation - WoS: 14
Citation - Scopus: 11
Standardized Definition of Progression Independent of Relapse Activity (Pira) in Relapsing-Remitting Multiple Sclerosis
(Amer Medical Assoc, 2025) Muller, Jannis; Sharmin, Sifat; Lorscheider, Johannes; Ozakbas, Serkan; Karabudak, Rana; Horakova, Dana; Kalincik, Tomas
Importance Progression independent of relapse activity (PIRA) is a significant contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (MS). Prior studies have used varying PIRA definitions, hampering the comparability of study results. Objective To compare various definitions of PIRA. Design, Setting, and Participants This cohort study involved a retrospective analysis of prospectively collected data from the MSBase registry from July 2004 to July 2023. The participants were patients with MS from 186 centers across 43 countries who had clinically definite relapsing-remitting MS, a complete minimal dataset, and 3 or more documented Expanded Disability Status Scale (EDSS) assessments. Exposure Three-hundred sixty definitions of PIRA as combinations of the following criteria: baseline disability (fixed baseline with re-baselining after PIRA, or plus re-baselining after relapses, or plus re-baselining after improvements), minimum confirmation period (6, 12, or 24 months), confirmation magnitude (EDSS score at/above worsening score or at/above threshold compared with baseline), freedom from relapse at EDSS score worsening (90 days prior, 90 days prior and 30 days after, 180 days prior and after, since previous EDSS assessment, or since baseline), and freedom from relapse at confirmation (30 days prior, 90 days prior, 30 days before and after, or between worsening and confirmation). Main Outcome and Measure For each definition, we quantified PIRA incidence and persistence (ie, absence of a 3-month confirmed EDSS improvement over >= 5 years). Results Among 87 239 patients with MS, 33 303 patients fulfilled the inclusion criteria; 24 152 (72.5%) were female and 9151 (27.5%) were male. At the first visits, the mean (SD) age was 36.4 (10.9) years; 28 052 patients (84.2%) had relapsing-remitting MS, and the median (IQR) EDSS score was 2.0 (1.0-3.0). Participants had a mean (SD) 15.1 (11.9) visits over 8.9 (5.2) years. PIRA incidence ranged from 0.141 to 0.658 events per decade and persistence from 0.753 to 0.919, depending on the definition. In particular, the baseline and confirmation period influenced PIRA detection. The following definition yielded balanced incidence and persistence: a significant disability worsening compared with a baseline (reset after each PIRA event, relapse, and EDSS score improvement), in absence of relapses since the last EDSS assessment, confirmed with EDSS scores (not preceded by relapses within 30 days) that remained above the worsening threshold for at least 12 months. Conclusion and Relevance Incidence and persistence of PIRA are determined by the definition used. The proposed standardized definition aims to enhance comparability among studies.