No evidence of disease activity in multiple sclerosis: Implications on cognition and brain atrophy

2015 ◽  
Vol 22 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Alfredo Damasceno ◽  
Benito Pereira Damasceno ◽  
Fernando Cendes
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Atrophy ◽  
Repeated Measures ◽  
Positive Impact ◽  
Cognitive Domains ◽  
Cortical Thinning ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Volume Decrease

Background: The concept of no evidence of disease activity (NEDA) has emerged as an important outcome measure for multiple sclerosis (MS). However, it is not known if maintaining NEDA has a positive impact on cognition or brain atrophy. Objective: To evaluate NEDA status after two years, addressing its implications on cognition and brain atrophy. Methods: Forty-two relapsing–remitting MS patients and 30 controls underwent MRI (3T) and cognitive evaluation (BRB-N). Forty patients performed additional evaluations, after 12 and 24 months. NEDA was defined as the absence of clinical (relapses/disability progression) and MRI activity (new T2/gadolinium-enhancing lesions). Repeated measures and multivariate analyses were performed to assess the contribution of NEDA criteria to GM atrophy. Results: After two years, 30.8% of the cohort had NEDA. From these, 58.3% still had worsening in ⩾2 cognitive domains. Patients with MRI activity had more cortical thinning and slightly more thalamus volume decrease. Absence of new/enlarging T2 lesions was the only predictor of cortical thinning, subcortical GM and thalamic atrophy rates. Conclusions: NEDA status was achieved in a small proportion of our cohort, and did not preclude cognitive deterioration. Absence of MRI activity and especially of new/enlarging T2 lesions was associated with less cortical and subcortical GM atrophy.

scholarly journals Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study

2018 ◽  
Vol 25 (6) ◽  
pp. 819-827 ◽  
Author(s):  
Gavin Giovannoni ◽  
Per Soelberg Sorensen ◽  
Stuart Cook ◽  
Kottil W Rammohan ◽  
Peter Rieckmann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
High Disease Activity ◽  
Study Entry ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Study Population ◽  
Magnetic Resonance Imaging Mri ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

Background: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Objective: Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Methods: Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). Results: In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Conclusion: Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.

Minimal evidence of disease activity (MEDA) in relapsing-remitting multiple sclerosis

2020 ◽  
Vol 91 (3) ◽  
pp. 271-277 ◽  
Author(s):  
Luca Prosperini ◽  
Chiara Mancinelli ◽  
Shalom Haggiag ◽  
Cinzia Cordioli ◽  
Laura De Giglio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Second Year ◽  
Remitting Multiple Sclerosis ◽  
A Minor ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Minimal Evidence

ObjectiveThis study aimed to define the minimal evidence of disease activity (MEDA) during treatment that can be tolerated without exposing patients with relapsing-remitting multiple sclerosis at risk of long-term disability.MethodsWe retrospectively collected data of patients followed up to 10 years after starting interferon beta or glatiramer acetate. Survival analyses explored the association between the long-term risk of reaching an Expanded Disability Status Scale≥6.0 and early clinical and MRI activity assessed after the first and second year of treatment. Early disease activity was classified by the so-called ‘MAGNIMS score’ (low: no relapses and <3 new T2 lesions; medium: no relapses and ≥3 new T2 lesions or 1 relapse and 0–2 new T2 lesions; high: 1 relapse and ≥3 new T2 lesions or ≥2 relapses) and the absence or presence of contrast-enhancing lesions (CELs).ResultsAt follow-up, 148/1036 (14.3%) patients reached the outcome: 61/685 (8.9%) with low score (reference category), 57/241 (23.7%) with medium score (HR=1.94, p=0.002) and 30/110 (27.3%) with high score (HR=2.47, p<0.001) after the first year of treatment. In the low score subgroup, the risk was further reduced in the absence (49/607, 8.1%) than in the presence of CELs (12/78, 15.4%; HR=2.11, p=0.01). No evident disease activity and low score in the absence of CELs shared the same risk (p=0.54). Similar findings were obtained even after the second year of treatment.ConclusionsEarly marginal MRI activity of one to two new T2 lesions, in the absence of both relapses and CELs, is associated with a minor risk of future disability, thus representing a simple and valuable definition for MEDA.

060 Association of brain volume loss and neda outcomes in patients with relapsing multiple sclerosis in the opera i and opera ii studies (ENCORE)

2018 ◽  
Vol 89 (6) ◽  
pp. A25.1-A25
Author(s):  
Anthony Traboulsee ◽  
Douglas Arnold ◽  
Eric C Klawiter ◽  
Eva Havrdova ◽  
Damian Fiore ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Tissue ◽  
Repeated Measures ◽  
Brain Volume ◽  
Brain Mri ◽  
Treatment Goal ◽  
Volume Loss ◽  
T2 Lesions ◽  
Brain Volume Loss

IntroductionBrain volume loss (BVL) occurs in multiple sclerosis (MS) patients, reflecting irreversible tissue damage. No evidence of disease activity (NEDA), a composite measure assessing absence of clinical and magnetic resonance imaging (MRI) disease activity has emerged as important treatment goal in MS and may be associated with preservation of brain tissue and BVL prevention.MethodsPatients in OPERA-I/II (NCT01247324/NCT01412333) received 600 mg ocrelizumab (intravenous) very 24 weeks or 44 µg subcutaneous interferon beta-1a (IFNβ-1a) 3x-weekly for 96 weeks. Brain MRI assessments were completed at baseline and 24/48/96 Weeks. Brain volume normalised for head size was measured using SIENAX software. Percent change in whole brain volume (WBV) was determined using SIENA software, changes in cortical grey (GMV) and white (WMV) matter volumes were measured using validated, locally developed Jacobian integrator atrophy software. NEDA was defined as absence of relapses, 12-week confirmed disability progression, T1 Gd–enhancing lesions and new and/or enlarging T2-lesions. Changes from baseline in brain volume were examined in NEDA patients and those with evidence of disease activity (EDA), using the mixed-effects model for repeated measures method.ResultsThe analysis included 1520 patients (ocrelizumab-761; IFNβ-1a-759). Over 96 weeks, 569 (37%) patients [ocrelizumab-363 (48%); IFNβ-1a-206(27%); p<0.001] had NEDA. Compared with EDA patients, NEDA patients had significantly less WBV loss from baseline (30%-reduction; p<0.001). In the NEDA group, ocrelizumab patients had significantly less WBV loss (32%-reduction; p<0.001), WMV loss (34%-reduction; p=0.044) and GMV loss (30%-reduction; p<0.001) from baseline than IFNβ-1a patients. In the EDA group, ocrelizumab patients had significantly less WBV loss (11%-reduction; p=0.047) and GMV loss (21%-reduction; p<0.001) but not WMV loss (1.03%-increase; p=0.90) from baseline than IFNβ-1a patients.ConclusionThese findings highlight the importance of NEDA as treatment goal with respect to brain tissue preservation regardless of treatment choice. Ocrelizumab may confer additional benefits in NEDA patients NEDA beyond what is observed with IFNβ-1a.

scholarly journals Іmpact of pathogenic therapy of multiple sclerosis on clinical and neuroimaging factors of its activity

2021 ◽  
pp. 39-42
Author(s):  
T. A. Kobys
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Neuroprotective Effect ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
T2 Lesions ◽  
Line Therapy ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

The article presents the experience of the Kiev Center of Multiple Sclerosis in using pathogenic first-line and second-line therapy to treat patients with relapsing-remitting multiple sclerosis (RRMS). We have analyzed clinical and neuroimaging factors of disease activity (relapse rate, changes in T2 lesions, Gd+ lesions) to assess the efficacy of the treatment during 24 months. Based on the NAA/Cr ratio we determined the neuroprotective effect of the therapy. The significant effect of pathogenic treatment is associated with both decrease in relapse frequency and with a slowdown in the emergence of new T2 and Gd+ lesions.

scholarly journals Blood neurofilament light chain as a biomarker of MS disease activity and treatment response

Neurology ◽  
2019 ◽  
Vol 92 (10) ◽  
pp. e1007-e1015 ◽  
Author(s):  
Jens Kuhle ◽  
Harald Kropshofer ◽  
Dieter A. Haering ◽  
Uma Kundu ◽  
Rolf Meinert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Response ◽  
Light Chain ◽  
Healthy Controls ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo assess the value of blood neurofilament light chain (NfL) as a biomarker of recent, ongoing, and future disease activity and tissue damage and its utility to monitor treatment response in relapsing-remitting multiple sclerosis.MethodsWe measured NfL in blood samples from 589 patients with relapsing-remitting multiple sclerosis (from phase 3 studies of fingolimod vs placebo, FREEDOMS and interferon [IFN]-β-1a, TRANSFORMS) and 35 healthy controls and compared NfL levels with clinical and MRI-related outcomes.ResultsAt baseline, NfL levels (pg/mL) were higher in patients than in healthy controls (30.5 and 27.0 vs 16.9, p = 0.0001) and correlated with T2 lesion load and number of gadolinium-enhancing T1 lesions (p < 0.0001, both). Baseline NfL levels, treatment, and number of new or enlarging T2 lesions during the studies predicted NfL levels at the end of study (all p < 0.01). High vs low baseline NfL levels were associated (estimate [95% confidence interval]) with an increased number of new or enlarging T2 lesions (ratio of mean: 2.64 [1.51–4.60]; p = 0.0006), relapses (rate ratio: 2.53 [1.67–3.83]; p < 0.0001), brain volume loss (difference in means: −0.78% [−1.02 to −0.54]; p < 0.0001), and risk of confirmed disability worsening (hazard ratio: 1.94 [0.97–3.87]; p = 0.0605). Fingolimod significantly reduced NfL levels already at 6 months (vs placebo 0.73 [0.656–0.813] and IFN 0.789 [0.704–0.884]), which was sustained until the end of the studies (vs placebo 0.628 [0.552–0.714] and IFN 0.794 [0.705–0.894]; p < 0.001, both studies at all assessments).ConclusionsBlood NfL levels are associated with clinical and MRI-related measures of disease activity and neuroaxonal damage and have prognostic value. Our results support the utility of blood NfL as an easily accessible biomarker of disease evolution and treatment response.

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.

scholarly journals Discontinuation and dose reduction of rituximab in relapsing–remitting multiple sclerosis

2021 ◽  
Author(s):  
Malin Boremalm ◽  
Peter Sundström ◽  
Jonatan Salzer
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Dose Reduction ◽  
Inflammatory Disease ◽  
University Hospital ◽  
Full Dose ◽  
Reduced Dose ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Abstract Background Rituximab is safe and effective for treating relapsing–remitting multiple sclerosis (RRMS) according to phase II and observational studies. There are limited data on disease activity after discontinuation and dose reduction. The objective of this study was to evaluate the effects on inflammatory disease activity after discontinuation or dose reduction of rituximab in patients with RRMS or clinically isolated syndrome (CIS). Methods In this retrospective observational study, we included all RRMS and CIS patients ever treated with rituximab at the University Hospital of Umeå who had either; (1) discontinued treatment at any time or (2) reduced the dose to a mean of < 1000 mg yearly. The patients served as their own controls by contributing patient years on full dose, reduced dose, and off treatment. Results A total of 225 patients treated with mean (SD) 6256 (2456) mg rituximab during mean (SD) 6.5 (2.0) years were included. There were no differences regarding the annualized relapse rates during full dose versus reduced dose or off treatment (0.02 versus < 0.01 and 0.02, p = 0.09), neither regarding proportion MRI scans with new or enlarged T2 lesions (0.03 versus 0.01 and 0.03, p = 0.37) or contrast-enhancing lesions (< 0.01 versus 0 and 0.02, p = 0.22). Conclusions This study indicates that rituximab has long-term effects on inflammatory disease activity and that disease reactivation is rare in MS patients who discontinued treatment for any reason. It also suggests that treatment with low-dose rituximab (< 1000 mg yearly) is sufficient to maintain suppression of inflammatory disease activity in patients with stable disease.

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