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 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.

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.

EFFECT OF FINGOLIMOD VS. IFN-BETA1A ON NO EVIDENCE OF DISEASE ACTIVITY

2015 ◽  
Vol 86 (11) ◽  
pp. e4.18-e4
Author(s):  
E Silber ◽  
X Montalban ◽  
F Barkhof ◽  
B Khatri ◽  
HP Hartung ◽  
...  
Keyword(s):  
Disease Activity ◽  
Interferon Beta ◽  
Brain Volume ◽  
Disability Progression ◽  
T2 Lesions ◽  
Brain Volume Loss ◽  
Relapsing Remitting ◽  
Balanced Measure ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

IntroductionTo compare effects of fingolimod vs. interferon beta-1a (IFN) in achieving no evidence of disease activity (NEDA-4) in patients with relapsing-remitting multiple sclerosis (RRMS) in the TRANSFORMS study. Adding Brain Volume Loss (BVL) to NEDA results in a more comprehensive and balanced measure of focal and diffuse damage.MethodsIn this post-hoc analysis, we used data from the fingolimod 0.5 mg daily (n=431) and IFN 30 µg weekly (n=435) groups. NEDA-4 was defined as absence of confirmed relapses, new/enlarging T2 lesions, 6-month confirmed disability progression (CDP) and BVL (annual percent brain volume change [PBVC] of >−0.4%). 3-month CDP and additional PBVC cut-offs representing mean BVL rates in healthy adults (0.2%), MS patients (0.6%), or accelerated BVL (1.2%) were also tested. Odds ratios (OR) were calculated for differences between fingolimod- and IFN-treated groups.ResultsSignificantly more fingolimod (n=425) than IFN-treated patients (n=418) achieved NEDA-4 status: 27.9% vs. 16.7% (OR:1.93; 95% CI: 1.36–2.73; p=0.0002). Results were similar for other PBVC cut-offs: (>–0.2%): 20.2% vs 11.5%; 1.94; 1.30–2.90, p=0.0011; (>–0.6%): 34.6% vs 20.4%; 2.06; 1.49–2.86, p<0.0001; (>–1.2%): 40.8% vs 26.4%; 1.92; 1.42–2.60; p<0.0001.ConclusionFingolimod-treated patients had twice the odds of achieving NEDA-4 status over 1 year as patients treated with IFN.

scholarly journals A Delphi panel on treatment of high disease activity relapsing remitting multiple sclerosis in the Netherlands

2020 ◽  
Author(s):  
Renée E Michels ◽  
Michel L Peters ◽  
Krijn MH Schiffers ◽  
Paul A Bouma ◽  
Gerald ID Hengstman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
The Netherlands ◽  
Disease Activity ◽  
High Disease Activity ◽  
Delphi Panel ◽  
Online Questionnaire ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Aim: To gain insight into current treatment and barriers to optimal treatment for high disease activity relapsing remitting multiple sclerosis (MS) in the Netherlands. Materials & methods: A two-round Delphi panel using an online questionnaire was conducted. Seven MS neurologists from diverse locations in the Netherlands were invited to participate. Result: Out of the seven MS neurologists, five completed both questionnaire rounds. Conclusion: Effectiveness and side effects along with patient’s lesion load were the most important factors for choosing a disease modifying therapy (DMTs). Respondents felt restricted to optimally treat their patients due to reimbursement restrictions for certain disease modifying therapies, although agreed that satisfactory treatment options are currently available. The answers show consensus between the participating MS neurologists with high certainty of answers.

scholarly journals Clinical and MRI efficacy of sc IFN β-1a tiw in patients with relapsing MS appearing to transition to secondary progressive MS: post hoc analyses of PRISMS and SPECTRIMS

2019 ◽  
Vol 267 (1) ◽  
pp. 64-75
Author(s):  
Mark S. Freedman ◽  
Staley Brod ◽  
Barry A. Singer ◽  
Bruce A. Cohen ◽  
Brooke Hayward ◽  
...  
Keyword(s):  
Disease Activity ◽  
Disability Progression ◽  
Secondary Progressive ◽  
T2 Lesions ◽  
Baseline Activity ◽  
Point Increase ◽  
Relapsing Remitting ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Clinical Mri

Abstract This study evaluated efficacy of subcutaneous (sc) interferon beta-1a (IFN β-1a) 44 µg 3 × weekly (tiw) in patients appearing to transition from relapsing–remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS). The PRISMS study included 560 patients with RRMS (EDSS 0–5.0; ≥ 2 relapses in previous 2 years), and the SPECTRIMS study included 618 patients with SPMS (EDSS 3.0–6.5 and ≥ 1-point increase in previous 2 years [≥ 0.5 point if 6.0–6.5]) randomly assigned to sc IFN β-1a 44 or 22 µg or placebo for 2–3 years, respectively. These post hoc analyses examined five subgroups of MS patients with EDSS 4.0–6.0: PRISMS (n = 59), PRISMS/SPECTRIMS (n = 335), PRISMS/SPECTRIMS with baseline disease activity (n = 195; patients with either ≥ 1 relapse within 2 years before baseline or ≥ 1 gadolinium-enhancing lesion at baseline), PRISMS/SPECTRIMS without baseline disease activity (n = 140), and PRISMS/SPECTRIMS with disease activity during the study (n = 202). In the PRISMS and PRISMS/SPECTRIMS subgroups, sc IFN β-1a delayed disability progression, although no significant effect was observed in PRISMS/SPECTRIMS subgroups with activity at baseline or activity during the study (regardless of baseline activity). In the PRISMS/SPECTRIMS subgroup, over year 1 (0–1) and 2 (0–2), sc IFN β-1a 44 µg tiw significantly reduced annualized relapse rate (p ≤ 0.001), and relapse risk (p < 0.05) versus placebo. Similar results were seen for the PRISMS/SPECTRIMS with baseline disease activity subgroup. Subcutaneous IFN β-1a reduced T2 burden of disease and active T2 lesions in the PRISMS/SPECTRIMS subgroups overall, with and without baseline activity. In conclusion, these post hoc analyses indicate that effects of sc IFN β-1a 44 µg tiw on clinical/MRI endpoints are preserved in a patient subgroup appearing to transition between RRMS and SPMS.

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.

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