scholarly journals Efficacy of alemtuzumab in relapsing-remitting MS patients who received additional courses after the initial two courses: Pooled analysis of the CARE-MS, extension, and TOPAZ studies

2019 ◽  
Vol 26 (14) ◽  
pp. 1866-1876 ◽  
Author(s):  
Giancarlo Comi ◽  
Raed Alroughani ◽  
Aaron L Boster ◽  
Ann D Bass ◽  
Regina Berkovich ◽  
...  
Keyword(s):  
Disease Activity ◽  
Pooled Analysis ◽  
Resonance Imaging ◽  
Exclusion Criteria ◽  
Disease Modifying Therapy ◽  
Safety Risks ◽  
Improved Outcomes ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri

Background: Alemtuzumab is given as two annual courses. Patients with continued disease activity may receive as-needed additional courses. Objective: To evaluate efficacy and safety of additional alemtuzumab courses in the CARE-MS (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis) studies and their extensions. Methods: Subgroups were based on the number of additional alemtuzumab courses received. Exclusion criteria: other disease-modifying therapy (DMT); <12-month follow-up after last alemtuzumab course. Results: In the additional-courses groups, Courses 3 and 4 reduced annualized relapse rate (12 months before: 0.73 and 0.74, respectively; 12 months after: 0.07 and 0.08). For 36 months after Courses 3 and 4, 89% and 92% of patients were free of 6-month confirmed disability worsening, respectively, with 20% and 26% achieving 6-month confirmed disability improvement. Freedom from magnetic resonance imaging (MRI) disease activity increased after Courses 3 and 4 (12 months before: 43% and 53%, respectively; 12 months after: 73% and 74%). Safety was similar across groups; serious events occurred irrespective of the number of courses. Conclusion: Additional alemtuzumab courses significantly improved outcomes, without increased safety risks, in CARE-MS patients with continued disease activity after Course 2. How this compares to outcomes if treatment is switched to another DMT instead remains unknown.

Efficacy of rituximab in refractory RRMS

2018 ◽  
Vol 25 (6) ◽  
pp. 828-836 ◽  
Author(s):  
Pierre Durozard ◽  
Adil Maarouf ◽  
Clémence Boutiere ◽  
Aurelie Ruet ◽  
Bruno Brochet ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Rescue Therapy ◽  
Outcome Data ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Retrospective Multicenter Study

Objective: To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT). Methods: In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months. Outcome data were collected from the French Observatory of Multiple Sclerosis (OFSEP) register and medical charts. Results: A total of 50 patients were identified. Median rituximab treatment duration was 1.1 (0.5–6.4) year. Mean annualized relapse rate significantly decreased from 0.8 during last immunosuppressive DMT to 0.18 after rituximab ( p < 0.0001). While 72% of patients showed gadolinium-enhancing lesions on the last MRI performed during last immunosuppressive DMT, 8% of them showed gadolinium-enhancing lesions on the first MRI performed 6.1 (range 1.4–18.4) months after rituximab ( p < 0.0001). Conclusion: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.

Measures in the first year of therapy predict the response to interferon β in MS

2009 ◽  
Vol 15 (7) ◽  
pp. 848-853 ◽  
Author(s):  
J Río ◽  
J Castilló ◽  
A Rovira ◽  
M Tintoré ◽  
J Sastre-Garriga ◽  
...  
Keyword(s):  
Disease Activity ◽  
Logistic Model ◽  
First Year ◽  
Interferon Β ◽  
Clinical Predictors ◽  
Predictors Of Response ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background and objective Several criteria for treatment response to interferon beta (IFNβ) have been proposed, although there is no consensus among different investigators. Hence, the aim of this study was to investigate magnetic resonance imaging (MRI) and clinical predictors of response during the first 12 months of therapy. Methods This is a prospective and longitudinal study of relapsing-remitting multiple sclerosis (RRMS) patients treated with IFNβ. Patients were classified based on the presence of new lesions on MRI, relapses, confirmed disability increase, or combinations of all these variables after 1 year of therapy. Regression analysis was performed in order to identify variables of response after a follow-up of 3 years. Results We included 222 RRMS patients. The logistic model demonstrated that only the combination of new active lesions on MRI with the presence of relapses (OR 4.4; 95% CI 1.6–12.5) or disability progression (Odds Ratio (OR) 7.1; 95% Confidence Interval (CI) 1.6–33.9), or both (OR 6.5; 95% CI 1.9–23.4) achieved significant values to identify those patients with a poor outcome. Conclusions In RRMS patients treated with IFNβ, the combination of measures of disease activity and the presence of new active lesions on MRI may have a prognostic value for identifying patients with disease activity in the second and third year of therapy.

scholarly journals Safety and Efficacy of Eculizumab Therapy in Multiple Sclerosis: A Case Series

2021 ◽  
Vol 11 (10) ◽  
pp. 1341
Author(s):  
Marco Allinovi ◽  
Angelo Bellinvia ◽  
Francesco Pesce ◽  
Sabrina Milan Manani ◽  
Lorenzo Razzolini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Case Series ◽  
Multicentric Study ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Before And After ◽  
System Activation ◽  
Ms Pathogenesis

(1) Background: Complement system activation has been proposed as one of the different factors that contribute to Multiple Sclerosis (MS) pathogenesis. In this study, we aimed to describe the potential effects of eculizumab, an anticomplement therapy, on MS disease activity in a cohort of relapsing–remitting (RR) MS patients who discontinued IFN-β therapy due to IFN-β-related thrombotic microangiopathy (TMA) onset. (2) Methods: In this retrospective observational multicentric study, we searched for all patients with MS treated by eculizumab with a survey of several nephrological and neurological centers (over 45 centers). (3) Results: Nine patients were included. The mean follow-up time under eculizumab was 3.72 ± 2.58 years. There were no significant differences in disease activity (EDSS, relapses, new T2, and/or Gd-enhancing lesions at MRI) considering the two years before and after eculizumab therapy. No adverse events potentially related to eculizumab therapy were reported during follow-up. (4) Conclusions: In this preliminary study, we described a good safety profile for eculizumab therapy in MS. However, the available data are not sufficient to make firm conclusions about the possible efficacy of eculizumab as a disease-modifying therapy for MS patients.

Does MRI lesion activity regress in secondary progressive multiple sclerosis?

2010 ◽  
Vol 16 (4) ◽  
pp. 434-442 ◽  
Author(s):  
Y. Zhao ◽  
AJ Petkau ◽  
A. Traboulsee ◽  
A. Riddehough ◽  
DKB Li
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Short Term ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri ◽  
Short Term Trend

Background: The rate of new contrast-enhancing lesions (CELs) on monthly magnetic resonance imaging (MRI) scans has been shown to decrease over a 9-month period in placebo-treated patients with relapsing—remitting (RR) multiple sclerosis (RRMS). Objective: We examined this phenomenon in placebo-treated secondary progressive MS (SPMS) patients. Methods: Patients were chosen from two clinical trials. Monthly scans were taken at screening, baseline and months 1—9 for Cohort-1 and months 1—6 for Cohort-2. We examined the monthly new CEL rates according to initial CEL level: 0, 1—3, >3 CELs at screening, and presence and absence of pre-study relapses. Results: Respectively, 59, 21 and 14 of the 94 Cohort-1 patients, and 36, 17 and 9 of the 62 Cohort-2 patients had 0, 1—3 and >3 initial CELs. For Cohort-1, the monthly new CEL rates did not change during follow-up, regardless of initial CEL level. For Cohort-2, the monthly rate was unchanged in the 0 initial CEL subgroup, but decreased 33% (95% confidence interval: 8%, 52%) from months 1—3 to months 4—6 in the other two subgroups. For the combined cohorts, a decreasing rate was observed in the 12 patients with >3 initial CELs and pre-study relapses. Conclusions: The short-term trend of new CEL activity in placebo-treated SPMS patients may vary across cohorts.

scholarly journals Ocrelizumab treatment for relapsing-remitting multiple sclerosis after a suboptimal response to previous disease-modifying therapy: A nonrandomized controlled trial

2021 ◽  
pp. 135245852110357
Author(s):  
Bianca Weinstock-Guttman ◽  
Robert Bermel ◽  
Gary Cutter ◽  
Mark S Freedman ◽  
Thomas P Leist ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Controlled Trial ◽  
Intention To Treat ◽  
T2 Lesions ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Activity Measures ◽  
Disease Modifying ◽  
Magnetic Resonance Imaging Mri

Background: Many patients with multiple sclerosis (MS) experience suboptimal disease control despite the use of disease-modifying therapy (DMT). Objective: To assess the efficacy and safety of ocrelizumab (OCR) in patients with relapsing-remitting MS (RRMS) and suboptimal response to prior DMTs. Methods: Patients with RRMS and suboptimal responses (one clinically reported relapse and/or lesion activity) after ⩾ 6 months on another DMT were enrolled. OCR 600 mg was given intravenously every 24 weeks. The primary outcome was no evidence of disease activity (NEDA), defined as the absence of protocol-defined relapse, confirmed disability progression (CDP), T1 Gd-enhancing lesions, and new/enlarging T2 lesions. Results: The intention-to-treat (ITT) population included 608 patients; NEDA was analyzed in a modified ITT (mITT) population ( n = 576 (94.7%)). Over 96 weeks, 48.1% of mITT patients achieved NEDA, and most were free from protocol-defined relapse (89.6%), CDP (89.6%), and T1 Gd-enhancing lesions (95.5%); 59.5% had no new/enlarging T2 lesions. Safety observations were consistent with findings in the pivotal trials. Conclusion: Consistent efficacy of OCR on clinical and magnetic resonance imaging (MRI) disease activity measures and progression was shown in patients with RRMS and a suboptimal response to prior DMTs; no new safety signals were observed.

scholarly journals Temporal profile of serum neurofilament light in multiple sclerosis: Implications for patient monitoring

2020 ◽  
pp. 135245852097257
Author(s):  
Peter A Calabresi ◽  
Douglas L Arnold ◽  
Dipen Sangurdekar ◽  
Carol M Singh ◽  
Arman Altincatal ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T2 Lesions ◽  
Disease Modifying Therapy ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Post Hoc

Objective: To understand how longitudinal serum neurofilament light chain (sNfL) patterns can inform its use as a prognostic biomarker in multiple sclerosis (MS) and evaluate whether sNfL reflects MS disease activity and disease-modifying therapy usage. Methods: This was a post hoc analysis of longitudinal data and samples from the ADVANCE trial (NCT00906399) of patients with relapsing–remitting MS (RRMS). sNfL was measured every 3 months for 2 years, then every 6 months for 4 years. Regression models explored how sNfL data predicted 4-year values of brain volume, expanded disability status scale score, and T2 lesions. sNfL levels were assessed in those receiving placebo, peginterferon beta-1a, and those with disease activity. Results: Baseline sNfL was a predictor of 4-year brain atrophy and development of new T2 lesions. Clinical ( p = 0.02) and magnetic resonance imaging (MRI) ( p < 0.01) outcomes improved in those receiving peginterferon beta-1a whose sNfL decreased to <16 pg/mL after 12 months versus those whose sNfL remained ⩾16 pg/mL. Mean sNfL levels decreased in peginterferon beta-1a-treated patients and increased in placebo-treated patients (–9.5% vs. 6.8%; p < 0.01). sNfL was higher and more variable in patients with evidence of active MS. Conclusion: These data support sNfL as a prognostic and disease-monitoring biomarker for RRMS.

Molecular detection of Parachlamydia-like organisms in cerebrospinal fluid of patients with multiple sclerosis

2008 ◽  
Vol 14 (4) ◽  
pp. 564-566 ◽  
Author(s):  
C Contini ◽  
S Seraceni ◽  
R Cultrera ◽  
M Castellazzi ◽  
E Granieri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity ◽  
Neurological Disorders ◽  
Chlamydia Pneumoniae ◽  
Molecular Detection ◽  
Resonance Imaging ◽  
Relapsing Remitting ◽  
Polymerase Chain ◽  
Magnetic Resonance Imaging Mri

The presence of Chlamydia-like organism DNA was investigated by polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) samples from 27 patients previously found positive for Chlamydia pneumoniae DNA: 12 with multiple sclerosis (MS), grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, 8 with other inflammatory neurological disorders and 7 with non-inflammatory neurological disorders. PCR evidence of Chlamydia-like organisms in CSF was observed only in two relapsing–remitting MS patients with clinical and MRI disease activity. These findings suggest a possible association between C. pneumoniae and Chlamydia-like organism brain infections as a cofactor in MS development.

scholarly journals Population-based study of “no evident disease activity” in MS

2018 ◽  
Vol 5 (6) ◽  
pp. e495 ◽  
Author(s):  
Natalie E. Parks ◽  
Sean J. Pittock ◽  
Jay Mandrekar ◽  
Orhun H. Kantarci ◽  
Claudia F. Lucchinetti ◽  
...  
Keyword(s):  
Disease Activity ◽  
Retrospective Chart Review ◽  
Population Based ◽  
Routine Care ◽  
Disease Modifying Therapy ◽  
Care Assessment ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Incident Cases

ObjectiveTo determine the persistence of no evident disease activity (NEDA) in a population-based relapsing-remitting MS (RRMS) cohort.MethodsAll incident cases of RRMS in Olmsted County between 2000 and 2011 were identified using a medical records linkage system. Persistence of NEDA after RRMS diagnosis was determined by retrospective chart review. MRI activity, relapse, or Expanded Disability Status Scale (EDSS) worsening resulted in failure of NEDA.ResultsWe identified 93 incident cases of RRMS including 82 individuals with sufficient follow-up to determine the persistence of NEDA. There were 44 individuals not on disease-modifying therapy (DMT), whereas 37 individuals were prescribed an injectable DMT and 1 received mitoxantrone during the interval over which NEDA was maintained. NEDA was maintained by 63% at 1 year, 38% at 2 years, 19% at 5 years, and 12% at 10 years according to routine care assessment. At 10 years, there was no difference in EDSS disability among patients who maintained NEDA vs those who failed NEDA at 1 year (p = 0.3).ConclusionsNEDA infrequently persists beyond 2 years in a population-based cohort of newly diagnosed patients with RRMS.

Longitudinal cortical thinning progression differs across multiple sclerosis phenotypes and is clinically relevant: A multicentre study

2020 ◽  
pp. 135245852094054
Author(s):  
Milagros Hidalgo de la Cruz ◽  
Paola Valsasina ◽  
Claudio Gobbi ◽  
Antonio Gallo ◽  
Chiara Zecca ◽  
...  
Keyword(s):  
Severe Disability ◽  
Cortical Atrophy ◽  
Group Differences ◽  
Lesion Volume ◽  
Resonance Imaging ◽  
Cortical Thinning ◽  
Relapsing Remitting ◽  
Weighted Magnetic Resonance Imaging ◽  
Magnetic Resonance Imaging Mri

Background: Longitudinal evolution of cortical thickness (CTh) in different MS phenotypes has been rarely studied. Aim: To investigate the regional pattern and 1-year progression of cortical thinning in relapsing-remitting (RR) and progressive (P) MS. Methods: 3T high-resolution T1-weighted magnetic resonance imaging (MRI) was obtained from 86 patients (75 RRMS, 11 PMS) and 34 healthy controls (HC) at three European sites at baseline and 1-year follow-up. Using FreeSurfer, baseline CTh between-group differences, longitudinal CTh changes and their correlations with clinical and MRI variables were assessed. Results: Baseline frontal, parietal and sensorimotor atrophy was found in MS versus HC. Such pattern was driven by RRMS, while PMS showed additional parietal, insular and sensorimotor cortical atrophy versus RRMS. At 1-year versus baseline, additional frontal and temporal cortical thinning was detected in RRMS patients, while a widespread CTh reduction was found in PMS patients (significant at time-by-group interaction vs RRMS). In MS, baseline fronto-parietal atrophy correlated with more severe disability and higher lesion volume. Baseline inferior parietal CTh decrease and 1-year temporal cortical thinning correlated with more severe disability. Conclusion: Parieto-temporal baseline CTh abnormalities and thinning pattern over time characterized the main MS clinical phenotypes and were associated with 1-year disability worsening.

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