Disability progression markers over 6–12 years in interferon-β-treated multiple sclerosis patients

2017 ◽  
Vol 24 (3) ◽  
pp. 322-330 ◽  
Author(s):  
Jordi Río ◽  
Àlex Rovira ◽  
Mar Tintoré ◽  
Susana Otero-Romero ◽  
Manuel Comabella ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Clinical Activity ◽  
Cox Models ◽  
Clinical Cohort ◽  
T2 Lesions ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Objective: To investigate the association between activity during interferon-beta (IFNβ) therapy and disability outcomes in patients with relapsing–remitting multiple sclerosis (RRMS). Methods: A longitudinal study based on two previously described cohorts of IFNβ-treated RRMS patients was conducted. Patients were classified according to clinical activity after 2 years (clinical cohort) or to clinical and radiological activity after 1 year (magnetic resonance imaging (MRI) cohort). Multivariate Cox models were calculated for early disease activity predicting long-term disability. Results: A total of 516 patients from two different cohorts were included in the analyses. Persistent clinical disease activity during the first 2 years of therapy predicted severe long-term disability (clinical cohort). In the MRI cohort, modified Rio score and no or minimal evidence of disease activity (NEDA/MEDA) did not identify patients with risk of Expanded Disability Status Scale (EDSS) worsening. However, a Rio score ≥ 2 (hazard ratio (HR): 3.3, 95% confidence interval (CI): 1.7–6.4); ≥3 new T2 lesions (HR: 2.9, 95% CI: 1.5–5.6); or ≥2 Gd-enhancing lesions (HR: 2.1, 95% CI: 1.1–4) were able to identify patients with EDSS worsening. Conclusion: Although early activity during IFNβ therapy is associated with poor long-term outcomes, minimal degree of activity does not seem to be predictive of EDSS worsening over 6.7-year mean follow-up.

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.

α-Linolenic acid is associated with MRI activity in a prospective cohort of multiple sclerosis patients

2018 ◽  
Vol 25 (7) ◽  
pp. 987-993 ◽  
Author(s):  
Kjetil Bjornevik ◽  
Kjell-Morten Myhr ◽  
Antonie Beiske ◽  
Kristian S Bjerve ◽  
Trygve Holmøy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Linolenic Acid ◽  
Statistical Significance ◽  
Serum Levels ◽  
T2 Lesions ◽  
Random Intercept ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Sclerosis Patients

Background: The plant-based ω-3 fatty acid α-linolenic acid (ALA) has been associated with lower MS risk. It is currently unknown whether ALA affects disease activity. Objective: To investigate the association between ALA levels and disease activity. Methods: We conducted a cohort study including 87 multiple sclerosis (MS)-patients who originally participated in a randomized trial of ω-3 fatty acids (the OFAMS study). We measured serum levels of ALA during follow-up and used random intercept logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association between ALA levels, new magnetic resonance imaging (MRI) lesions, Expanded Disability Status Scale (EDSS) progression and new relapses adjusting for age at inclusion, sex, and use of interferon beta-1a. Results: In continuous (per 1-SD increase) multivariable-adjusted analyses, higher ALA levels were significantly associated with lower odds of new T2-lesions (OR: 0.59, 95% CI: 0.37–0.95) during follow-up. The effect estimates were similar for new T1Gd + lesions (OR: 0.73, 95% CI: 0.48–1.11), EDSS-progression (OR: 0.62, 95% CI: 0.34–1.16) and new relapses (OR: 0.49, 95% CI: 0.22–1.10), but these estimates did not reach statistical significance. Further adjustment for vitamin D and tobacco use did not materially change the results. Conclusion: We found that higher levels of ALA were associated with lower disease activity in MS-patients.

scholarly journals Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731882461
Author(s):  
Stanley L Cohan ◽  
Keith Edwards ◽  
Lindsay Lucas ◽  
Tiffany Gervasi-Follmar ◽  
Judy O’Connor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Magnetic Resonance Imaging ◽  
T2 Lesions ◽  
Disability Status ◽  
The Mean ◽  
Multiple Sclerosis Patients ◽  
Mean Time ◽  
Relapsing Multiple Sclerosis

Background Natalizumab is an effective treatment for relapsing multiple sclerosis. Return of disease activity upon natalizumab discontinuance creates the need for follow-up therapeutic strategies. Objective To assess the efficacy of teriflunomide following natalizumab discontinuance in relapsing multiple sclerosis patients. Methods Clinically stable relapsing multiple sclerosis patients completing 12 or more consecutive months of natalizumab, testing positive for anti-John Cunningham virus antibody, started teriflunomide 14 mg/day, 28 ± 7 days after their final natalizumab infusion. Physical examination, Expanded Disability Status Scale, laboratory assessments, and brain magnetic resonance imaging were performed at screening and multiple follow-up visits. Results Fifty-five patients were enrolled in the study. The proportion of patients relapse-free was 0.94, restricted mean time to first gadolinium-enhancing lesion was 10.9 months and time to 3-month sustained disability worsening was 11.8 months. The mean number of new or enlarging T2 lesions per patient at 12 months was 0.42. Exploratory analyses revealed an annualized relapse rate of 0.08, and a proportion of patients with no evidence of disease activity of 0.68. Forty-seven patients (85.5%) reported adverse events, 95% of which were mild to moderate. Conclusions Teriflunomide therapy initiated without natalizumab washout resulted in a low rate of return of disease activity. Clinicians may consider this a worthwhile strategy when transitioning clinically stable patients off natalizumab to another therapy. ClinicalTrials.gov Identifier: NCT01970410

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