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

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.

scholarly journals Aging and efficacy of disease-modifying therapies in multiple sclerosis: a meta-analysis of clinical trials

2020 ◽  
Vol 13 ◽  
pp. 175628642096901
Author(s):  
Yinan Zhang ◽  
Natalia Gonzalez Caldito ◽  
Afsaneh Shirani ◽  
Amber Salter ◽  
Gary Cutter ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Disease Activity ◽  
Meta Analysis ◽  
Group Level ◽  
T2 Lesions ◽  
Disease Modifying Therapies ◽  
Level Data ◽  
Disease Modifying ◽  
Magnetic Resonance Imaging Mri

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for the treatment of disease activity and are effective in reducing relapses and new magnetic resonance imaging (MRI) lesions. However, disease activity generally subsides with time, and age-dependent changes in DMT efficacy are not well-established. We aimed to investigate whether age impacts the efficacy of DMTs in treating disease activity in patients with relapsing–remitting MS (RRMS). Methods: DMT efficacy related to age was assessed through a meta-analysis of clinical trials that evaluated the efficacy of DMTs in RRMS patients as measured by reductions in the annualized relapse rate (ARR), new T2 lesions, and gadolinium-enhanced lesions on MRI. Using the mean baseline patient age from each trial, a weighted linear regression was fitted to determine whether age was associated with treatment efficacy on a group level. Results: Group-level data from a total of 28,082 patients from 26 trials of 14 different DMTs were included in the meta-analysis. There were no statistically significant associations between age and reductions in ARR, new T2 lesions, and gadolinium-enhanced lesions of the treatment group compared with placebo. Conclusion: DMTs for RRMS show efficacy in treating disease activity independent of age as demonstrated by group-level data from DMT clinical trials. Nevertheless, clinical trials select for patients with baseline disease activity regardless of age, thereby not representing real-world patients with RRMS, where disease activity declines with age.

Intrathecal synthesis of soluble HLA-G and HLA-I molecules are reciprocally associated to clinical and MRI activity in patients with multiple sclerosis

2006 ◽  
Vol 12 (1) ◽  
pp. 2-12 ◽  
Author(s):  
E Fainardi ◽  
R Rizzo ◽  
L Melchiorri ◽  
M Castellazzi ◽  
E Paolino ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Neurological Disorders ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Concentrations ◽  
Intrathecal Synthesis ◽  
Soluble Hla ◽  
Elisa Technique ◽  
Magnetic Resonance Imaging Mri

The aim of this study was to provide further insight into the effective contribution of classical soluble HLA-A, B and C class Ia (sHLA-I) and non-classical soluble HLA-G class Ib (sHLA-G) molecules in immune dysregulation occurring in multiple sclerosis (MS). We evaluated by enzyme-linked immunosorbent assay (ELISA) technique intrathecal synthesis and cerebrospinal fluid (CSF) and serum levels of sHLA-I and sHLA-G in 69 relapsing-remitting (RR), 21 secondary progressive (SP) and 13 primary progressive (PP) MS patients stratified according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also tested, as neurological controls, 91 patients with other inflammatory neurological disorders (OIND) and 92 with non-inflammatory neurological disorders (NIND). Eighty-two healthy volunteers served as further controls for sHLA-I and sHLA-G determinations. An intrathecal production of sHLA-I and sHLA-G detected by specific indexes was significantly more frequent in MS patients than in controls (p<0.01). An intrathecal synthesis of sHLA-I was prevalent in clinically (p<0.02) and MRI active (p<0.001) MS, whereas a CSF-restricted release of sHLA-G predominated in clinically (p<0.01) and MRI stable (p<0.001) MS. sHLA-I levels were low in the serum of clinically active (p<0.001) and high in the CSF of MRI active (p<0.01) MS. Conversely, sHLA-G concentrations were decreased in the serum of clinically stable MS (p<0.01) and increased in the CSF of MRI inactive MS (p<0.001). The trends towards a negative correlation observed between CSF and serum concentrations and intrathecal synthesis of sHLA-I and sHLA-G in patients without evidence of clinical and MRI activity confirmed that intrathecal production and fluctuations in CSF and serum concentrations of sHLA-I and sHLA-G were reciprocal in MS. Our results suggest that, in MS, a balance between classical sHLA-I and non-classical sHLA-G products modulating both MRI and clinical disease activity in opposite directions may exist.

Interferon beta failure predicted by EMA criteria or isolated MRI activity in multiple sclerosis

2013 ◽  
Vol 20 (5) ◽  
pp. 566-576 ◽  
Author(s):  
Luca Prosperini ◽  
Chiara Rosa Mancinelli ◽  
Laura De Giglio ◽  
Floriana De Angelis ◽  
Valeria Barletta ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
European Medicines Agency ◽  
First Year ◽  
Resonance Imaging ◽  
T2 Lesions ◽  
Increased Risk ◽  
Magnetic Resonance Imaging Mri ◽  
One Year

Objective: The objective of this paper is to investigate four-year outcomes of interferon beta (IFNB)-treated patients with multiple sclerosis (MS) according to their clinical or magnetic resonance imaging (MRI) activity status at first year of treatment. Methods: A total of 370 patients with MS duration ≤5 years before IFNB start were followed-up for four years. The optimal threshold for one-year MRI activity that more accurately predicted subsequent relapses or disability worsening was identified. The risk of relapses and disability worsening after the first year was then estimated by propensity score (PS)-adjusted analyses in patients fulfilling European Medicines Agency (EMA) criteria for second-line escalation and in those with isolated MRI activity. Results: A total of 192 (51.9%) patients relapsed, and 66 (17.8%) worsened in disability from year 1 to 4 of follow-up. The more accurate threshold for one-year MRI activity was the occurrence of ≥1 enhancing or ≥2 new T2-lesions. An increased risk of relapses and disability worsening was found in either patients fulfilling EMA criteria (hazard ratio (HR) = 3.69, and HR = 6.02) and in those experiencing isolated MRI activity (HR = 3.15, and HR = 5.31) at first year of treatment, when compared with stable patients (all p values <0.001). Conclusion: The four-year outcomes of patients with isolated MRI activity did not differ from those fulfilling EMA criteria at first year of IFNB treatment.

scholarly journals Inflammatory activity and vitamin D levels in an MS population treated with rituximab

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731982659 ◽  
Author(s):  
Johan Linden ◽  
Gabriel Granåsen ◽  
Jonatan Salzer ◽  
Anders Svenningsson ◽  
Peter Sundström
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Magnetic Resonance ◽  
Vitamin D Supplementation ◽  
Inflammatory Activity ◽  
T2 Lesions ◽  
Vitamin D Levels ◽  
25 Hydroxy Vitamin D ◽  
Multiple Sclerosis Patients

Background Most multiple sclerosis patients on disease-modifying treatment at Umeå University Hospital are treated with rituximab and the prevalence of vitamin D supplementation has increased over time. Follow-up studies of these off-label treatments are needed. Objective To study inflammatory activity and adverse effects in rituximab-treated multiple sclerosis patients, and associations with 25-hydroxy-vitamin D levels. Methods Retrospectively collected data on repeated estimates of relapses, disability, side effects, magnetic resonance imaging, laboratory measures including 25-hydroxy-vitamin D levels and self-perceived health. Results In 272 multiple sclerosis patients with a mean follow-up of 43 months, we identified seven possible relapses during active rituximab treatment. On magnetic resonance imaging examination, new T2 lesions were seen in 1.3% (10 out of 792 scans), and 0.25% (two out of 785 scans) showed contrast enhancement. Adjusted 25-hydroxy-vitamin D levels in samples drawn close to all magnetic resonance images with new T2 lesions were lower compared to the remainder (62 vs. 81 nmol/l; P = 0.030). Levels of 25-hydroxy-vitamin D were associated with self-perceived health ( r = 0.18, P = 0.041, n = 130) and C-reactive protein ( r = –0.13, P = 0.042) but not with the risk of side effects. Conclusion The inflammatory activity in this rituximab-treated multiple sclerosis population that increasingly used vitamin D supplementation was extremely low. Higher 25-hydroxy-vitamin D levels were associated with beneficial outcomes.

Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis

2006 ◽  
Vol 12 (3) ◽  
pp. 294-301 ◽  
Author(s):  
E Fainardi ◽  
M Castellazzi ◽  
T Bellini ◽  
M C Manfrinato ◽  
E Baldi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Matrix Metalloproteinase ◽  
Disease Activity ◽  
Neurological Disorders ◽  
Serum Levels ◽  
Matrix Metalloproteinase 9 ◽  
Active Matrix ◽  
Magnetic Resonance Imaging Mri ◽  
Metalloproteinase 9

In this study, we employed a sensitive activity assay system to measure cerebrospinal fluid (CSF) and serum levels of active matrix metalloproteinase-9 (MMP-9) in 37 relapsing-remitting (RR), 15 secondary progressive (SP) and nine primary progressive (PP) multiple sclerosis (MS) patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also studied, as neurological controls, 48 patients with other inflammatory neurological disorders (OIND) and 48 with non-inflammatory neurological disorders (NIND). To assess active MMP-9/TIMP-1 circuit, CSF and serum levels of MMP-9 tissue inhibitor TIMP-1 were quantified by ELISA in the same patient population. CSF mean levels of active MMP-9, CSF active MMP-9/TIMP-1 ratios and intrathecal active MMP-9 synthesis, as indicated by specific index, were more elevated in MS than in NIND ( P <0.05, <0.02 and <0.02, respectively), serum active MMP-9/TIMP-1 ratio was higher in MS ( P<0.01) and OIND ( P<0.02) than in NIND, and serum TIMP-1 concentrations were lower in MS than in NIND ( P<0.05). More importantly, serum active MMP-9 mean levels, serum active MMP-9/TIMP-1 ratio and intrathecal production of active MMP-9 were increased in MS patients with clinical ( P<0.001, <0.001 and <0.05, respectively) and MRI ( P<0.001, <0.001 and <0.02, respectively) disease activity, whereas CSF mean concentrations of active MMP-9 and CSF active MMP-9/TIMP-1 ratio were enhanced only in MS patients with MRI evidence of disease activity ( P<0.02 and <0.01, respectively). Altogether, these findings suggest that a shift in MMP-9/TIMP-1 balance towards proteolytic activity of MMP-9 could be relevant in MS immune dysregulation. In addition, our results indicate that CSF and serum levels of active MMP-9 may represent a potential surrogate biomarker for monitoring MS disease activity. In particular, serum active MMP-9/TIMP-1 ratio seems to be a very appropriate indicator of ongoing MS inflammation, since it is easily measurable.

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.

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