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.

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 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.

scholarly journals Real-world experience of fingolimod in patients with multiple sclerosis (MS Fine): An observational study in the UK

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731880163
Author(s):  
Gordon Mazibrada ◽  
Charlotte Sharples ◽  
Ines Perfect
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Observational Study ◽  
Disease Activity ◽  
Relapse Rate ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
The Uk ◽  
Relapsing Remitting Multiple Sclerosis

Background Fingolimod is approved for the treatment of highly active relapsing–remitting multiple sclerosis in Europe. There is limited information on its effectiveness and safety in clinical practice within the UK. Objective To evaluate retrospectively the effectiveness and safety of fingolimod in patients with relapsing–remitting multiple sclerosis who were prescribed fingolimod by UK neurologists within the National Health Service. Methods This was a multicentre, observational study conducted in the UK. Patients were initiated on fingolimod 0.5 mg 12 months before inclusion in the study. Key efficacy outcomes included annualised relapse rate and the proportion of patients free from relapses, disability progression and clinical and radiological disease activity at 12 months following fingolimod initiation. Resource utilisation and safety outcomes were also assessed. Results In 12 months of treatment with fingolimod, the mean annualised relapse rate was reduced by 79%, the majority of patients were free from relapses (83.7%). Based on limited data, most patients were free from disability progression and clinical and radiological disease activity. More than 90% of patients continued on fingolimod. Lymphocyte count reductions and liver enzyme increases were observed. Conclusion Fingolimod was effective in reducing the disease activity in relapsing–remitting multiple sclerosis patients requiring an escalation from first-line therapies who were prescribed fingolimod in clinical practice in the UK.

Personalized extended interval dosing of natalizumab in MS

Neurology ◽  
2020 ◽  
Vol 95 (6) ◽  
pp. e745-e754
Author(s):  
Zoé L.E. van Kempen ◽  
Erwin L.J. Hoogervorst ◽  
Mike P. Wattjes ◽  
Nynke F. Kalkers ◽  
Jop P. Mostert ◽  
...  
Keyword(s):  
Disease Activity ◽  
Extension Phase ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Mri Scans ◽  
Secondary Endpoints ◽  
Trough Concentrations ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo determine whether natalizumab efficacy is maintained when switching to personalized extended interval dosing based on individual natalizumab trough concentrations in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsThis was a prospective multicenter single-arm trial with 1 year follow-up and a 1-year extension phase. Participants were adult persons with RRMS treated with natalizumab without disease activity in the year prior to enrollment. The natalizumab treatment interval was based on longitudinal natalizumab trough concentrations. Patients received 3 monthly MRI scans, relapse assessments, and disability scoring during follow-up. The primary endpoint was the occurrence of gadolinium-enhancing lesions on MRI. Secondary endpoints were new/enlarging T2 lesions on MRI and relapses and progression on the Expanded Disability Status Scale (EDSS) during follow-up and extension phase.ResultsSixty-one patients were included. Eighty-four percent extended the interval from a 4-week interval to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI] 0%–7.4%) during follow-up. No new/enlarging T2 lesions (95% CI 0%–7.4%) or relapses (95% CI 0%–7.4%) were reported during follow-up and in the extension phase. Median EDSS was comparable at baseline (3.0, interquartile range [IQR] 2.0–5.0) and after follow-up (3.0, IQR 2.0–5.0).ConclusionPersonalized extended interval dosing did not induce recurrence of MS disease activity. Natalizumab efficacy was maintained in stable patients with RRMS receiving personalized extended interval dosing based on individual natalizumab concentrations.Classification of evidenceThis study provides Class IV evidence that personalized extended interval dosing of natalizumab does not result in recurrence of disease activity in stable patients with RRMS.

Relationship between Sustained Disability Progression and Functional System Scores in Relapsing-Remitting Multiple Sclerosis: Analysis of Placebo Data from Four Randomized Clinical Trials

2015 ◽  
Vol 44 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Thomas Scott ◽  
Ping Wang ◽  
Xiaojun You ◽  
Monica Mann ◽  
Bjørn Sperling
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Functional System ◽  
Validity And Reliability ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

Background: The Expanded Disability Status Scale (EDSS), based on different functional system scores (FSS), remains the most frequently used disability assessment in relapsing-remitting multiple sclerosis (RRMS). In this analysis, we evaluated the relationship between sustained disability progression, measured by EDSS, and simultaneous changes in individual FSS domains. Methods: A post hoc analysis was performed on data from placebo-treated RRMS patients from four large, randomized, multicenter, phase 3 clinical trials. Sustained disability progression was defined as a ≥1.0-point EDSS score increase over a ≥3- or ≥6-month period. Simultaneous sustained disability progression and worsening of individual FSS domains was analyzed. Results: The majority of patients experienced sustained disability progression and simultaneous worsening of ≥1 FSS domain, with ≥1-point worsening in the pyramidal domain being most frequently associated with sustained disability progression (in 31-51% of patients), followed by ≥1-point worsening in the cerebellar (35-41% of patients) and sensory (31-45% of patients) domains. Conclusion: The key FSS components correlating with sustained disability progression, measured by EDSS, appear to be pyramidal, cerebellar, and sensory. In this analysis, the simultaneous worsening of consistent FSS domains confirms the validity and reliability of the use of sustained EDSS progression as a measure of disability progression.

067 Efficacy of cladribine tablets in patients with highly active relapsing-remitting multiple sclerosis: analysis of pooled double-blind data from the clarity and onward studies

2018 ◽  
Vol 89 (6) ◽  
pp. A27.2-A28
Author(s):  
Gavin Giovannoni ◽  
Xavier Montalban ◽  
Kottil Rammohan ◽  
Stuart Cook ◽  
Giancarlo Comi ◽  
...  
Keyword(s):  
Disease Activity ◽  
Placebo Treatment ◽  
Interferon Β ◽  
Double Blind ◽  
Highly Active ◽  
Relapsing Remitting ◽  
Mri Characteristics ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Efficacy Of Treatment

IntroductionPatients with relapsing MS (RMS) who show an increased rate of relapse or disability worsening can be described as showing high disease activity (HDA). Treatment with cladribine tablets (CT) in the CLARITY study, and with CT added to interferon-β in the ONWARD study demonstrated efficacy vs. placebo (PBO) across a range of patients with active MS. Combining double-blind data from these studies allows assessment of the efficacy of treatment with CT 3.5 mg/kg (CT3.5; cumulative dose). The objective of this post-hoc analysis is to compare the effects of CT3.5 vs. PBO on the proportion of patients achieving no evidence of disease activity (NEDA) status in HDA subgroups identified using two sets of criteria in a pooled cohort of patients from CLARITY and ONWARD.MethodsPatients from CLARITY and ONWARD were retrospectively stratified using 2 sets of HDA criteria based on relapse history, prior treatment, and MRI characteristics: high relapse activity (HRA; n=314) and HRA plus disease-activity-on-treatment (HRA +DAT; n=459). Patients treated with CT3.5 or PBO who fulfilled these criteria and achieved NEDA were compared over 2 years using odds ratios (ORs) and 95%CIs.ResultsIn the HRA subgroup, 76.5% of CT3.5-treated patients were relapse-free, 86.7% were T1 Gd +lesion free vs. 50.7% and 35.8%, respectively, for PBO. In the HRA +DAT subgroup, 77.6% were relapse-free and 88.8% were T1 Gd +lesion free with CT3.5 vs. 53.9% and 40.8%, respectively for PBO. In the HRA and HRA +DAT subgroups, 42.7% and 41.3%, respectively, of CT3.5-treated patients were disease activity free compared with 9.7%, (OR 6.94, 95% CI 3.67;13.12, p<0.0001) and 13.7% (OR 4.28, 95% CI 2.62;6.99, p<0.0001) respectively, of PBO recipients. In the overall CLARITY+ONWARD population (including non-HDA patients), the composite NEDA score also favoured CT over PBO (OR 3.95, 95% CI 2.90;5.37, p<0.0001).ConclusionCompared with placebo, treatment with CT3.5 was associated with increased odds of achieving NEDA in HDA patients.

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