Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis

2008 ◽  
Vol 14 (5) ◽  
pp. 663-670 ◽  
Author(s):  
T Vollmer ◽  
H Panitch ◽  
A Bar-Or ◽  
J Dunn ◽  
MS Freedman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Induction Therapy ◽  
Brain Magnetic Resonance Imaging ◽  
Short Term ◽  
Disability Status ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Forty relapsing multiple sclerosis patients with 1–15 gadolinium (Gd)-enhancing lesions on screening brain magnetic resonance imaging (MRI) and Expanded Disability Status Scale (EDSS) scores 0–6.5 were randomized to receive short-term induction therapy with mitoxantrone (three monthly 12 mg/m2 infusions) followed by 12 months of daily glatiramer acetate (GA) therapy 20 mg/day subcutaneously for a total of 15 months (M-GA, n = 21) or daily GA 20 mg/day for 15 months (GA, n = 19). MRI scans were performed at months 6, 9, 12 and 15. The primary measure of outcome was the incidence of adverse events; secondary measures included number of Gd-enhanced lesions, confirmed relapses and EDSS changes. Except age, baseline demographic characteristics were well matched in both treatment arms. Both treatments were safe and well tolerated. M-GA induction produced an 89% greater reduction (relative risk (RR) = 0.11, 95% confidence interval (CI): 0.04–0.36, p = 0.0001) in the number of Gd-enhancing lesions at months 6 and 9 and a 70% reduction (RR = 0.30, 95% CI: 0.11–0.86, p = 0.0147) at months 12 and 15 versus GA alone. Mean relapse rates were 0.16 and 0.32 in the M-GA and GA groups, respectively. Short-term immunosuppression with mitoxantrone followed by daily GA for up to 15 months was found to be safe and effective, with an early and sustained decrease in MRI disease activity.

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

scholarly journals Long-term efficacy and safety of three times weekly dosing regimen of glatiramer acetate in relapsing multiple sclerosis patients: Seven-year results of the Glatiramer Acetate Low-frequency Administration (GALA) open-label extension study

2021 ◽  
Vol 7 (4) ◽  
pp. 205521732110615
Author(s):  
Peter Rieckmann ◽  
Robert Zivadinov ◽  
Alexey Boyko ◽  
Krzysztof Selmaj ◽  
Jessica K. Alexander ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Low Frequency ◽  
Exposure Period ◽  
Similar Efficacy ◽  
Open Label ◽  
Open Label Extension ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Objective Describe the long-term outcomes of early-start (ES) and delayed-start (DS) glatiramer acetate 40 mg/mL treatment three times weekly (GA40) for up to seven years in the Glatiramer Acetate Low-frequency Administration (GALA) study in patients with relapsing multiple sclerosis (RMS). Methods Patients were evaluated every three to six months. The primary efficacy endpoint was annualized relapse rate (ARR); additional endpoints were exploratory or post hoc. For efficacy, data from the entire exposure period were used for the ES and DS cohorts. For safety, exposure only under GA40 was considered. Results Of the patients who continued into the open-label extension (OLE), 580/834 (70%) ES and 261/419 (62%) DS completed the OLE. For the entire placebo-controlled and OLE study period, ARR was 0.26 for ES and 0.31 for DS patients (risk ratio = 0.83; 95% confidence interval [CI]: 0.70–0.99). ES prolonged median time to first relapse versus DS (4.9 versus 4.3 years; hazard ratio = 0.82; 95% CI: 0.6–0.96). OLE-only results showed DS patients experienced similar efficacy for relapse and disability outcomes as ES patients. Adverse events were consistent with the well-established GA safety profile. Conclusions GA40 treatment conferred clinical benefit up to seven years, resulting in sustained efficacy and was generally well tolerated in RMS patients.

scholarly journals Rituximab vs placebo induction prior to glatiramer acetate monotherapy in multiple sclerosis

Neurology ◽  
2019 ◽  
Vol 92 (7) ◽  
pp. e723-e732 ◽  
Author(s):  
Justin M. Honce ◽  
Kavita V. Nair ◽  
Stefan Sillau ◽  
Brooke Valdez ◽  
Augusto Miravalle ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Controlled Study ◽  
Short Term ◽  
Double Blind ◽  
T2 Lesions ◽  
Time To Treatment Failure ◽  
Sustained Change ◽  
Baseline Characteristics ◽  
Relapsing Multiple Sclerosis

ObjectiveTo examine whether rituximab induction followed by glatiramer acetate (GA) monotherapy is more effective than GA alone for the treatment of relapsing multiple sclerosis with active disease.MethodsThis was a single-center, double-blind, placebo-controlled study. Fifty-five participants were randomly assigned (1:1 ratio) to either rituximab (R-GA) or placebo (P-GA) induction, followed by GA therapy initiated in all participants. Participants were followed up to 3 years. The primary endpoint was the number of participants with no evidence of disease activity (NEDA): those without relapse, new MRI lesions, and sustained change in disability.ResultsTwenty-eight and 27 participants received rituximab and placebo induction, respectively, with one participant in each arm withdrawing before 6-month MRI. There were no significant differences in baseline characteristics. At end of study, 44.44% of R-GA participants demonstrated NEDA vs 19.23% of P-GA participants (p = 0.049). Treatment failed for a smaller proportion of R-GA participants (37.04% R-GA vs 69.23% P-GA, p = 0.019), and time to treatment failure was longer (23.32 months R-GA vs 11.29 months P-GA, p = 0.027). Fewer participants in the R-GA arm had new lesions (25.93% R-GA vs 61.54% P-GA, p = 0.009), and there were fewer new T2 lesions (0.48 R-GA vs 1.96 P-GA, p = 0.027). Probability of demonstrating NEDA in the R-GA arm returned to baseline within the study period. There were no differences in adverse events.ConclusionsInduction therapy with rituximab followed by GA may provide superior efficacy in the short term than GA alone in relapsing multiple sclerosis, but this benefit appears to wane within the study period. Larger studies are needed to assess sustainability of results.ClinicalTrials.gov identifierNCT01569451.

Should frequent MRI monitoring be performed in natalizumab-treated MS patients? A contribution to a recent debate

2019 ◽  
Vol 26 (10) ◽  
pp. 1227-1236 ◽  
Author(s):  
Cristina Scarpazza ◽  
Alessio Signori ◽  
Mirco Cosottini ◽  
Maria Pia Sormani ◽  
Simonetta Gerevini ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Small Volume ◽  
Brain Magnetic Resonance Imaging ◽  
Available N ◽  
Disability Status ◽  
Mri Scans ◽  
Recent Debate ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Surveillance ◽  
The Impact

Background: Brain magnetic resonance imaging (MRI) is the most effective surveillance tool for the detection of asymptomatic progressive multifocal leukoencephalopathy (PML). However, the optimal frequency for routine MRI surveillance is under-investigated. Objective: To understand whether, upon their first MRI appearance, PML lesions present a difference in volume when comparing patients who frequently underwent MRI surveillance (3/4 months) with those who were assessed at longer intervals (6/12 months) and to understand the impact of the volume of lesions on clinical outcome. Methods: The data of patients included in the Italian PML cohort were retrospectively analysed. Patients who had all the pre-diagnostic MRI scans available ( n = 37) were included. The volume of PML lesion was calculated by manually outlining the PML lesion. Results: Compared with patients who underwent MRI examination at least every 4 months, patients who were assessed less frequently had a lesion of significantly higher volume (median: 2567 (883–3583) vs. 664 mm3 (392–963) p = 0.006) and suffered a higher rate of disability (median: 2.25 expanded disability status scale points (–2.5 to 8) vs. 0.5 (–1 to 2.5) p = 0.004). Conclusion: The positive clinical outcome of patients undergoing frequent MRI surveillance and the small volume of the PML lesion upon first appearance justify a frequent surveillance using MRI in patients at high risk of PML.

Three-year clinical outcomes of relapsing multiple sclerosis patients treated with dimethyl fumarate in a United States community health center

2017 ◽  
Vol 24 (7) ◽  
pp. 942-950 ◽  
Author(s):  
Kyle Smoot ◽  
Kateri J Spinelli ◽  
Tamela Stuchiner ◽  
Lindsay Lucas ◽  
Chiayi Chen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Community Health Center ◽  
Dimethyl Fumarate ◽  
Clinical Relapse ◽  
Disease Modifying Therapy ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Sclerosis Patients ◽  
Previous Disease ◽  
Relapsing Multiple Sclerosis

Background: Following approval of dimethyl fumarate (DMF), we established a registry of relapsing multiple sclerosis (RMS) patients taking DMF at our community MS center. Objective: To track DMF patients’ tolerability, disease progression, and lymphopenia. Methods: Patients prescribed DMF for RMS from March 2013 to March 2016 were prospectively enrolled ( N = 412). Baseline data, clinical relapses, magnetic resonance imaging (MRI) activity, discontinuation, and lymphocyte counts were captured through chart review. Results: The mean age of patients starting DMF was 49.4 ± 12.0 years and 70% transitioned from a previous disease-modifying therapy (DMT). Of the patients, 38% discontinued DMF, 76% of whom discontinued due to side effects. Clinical relapse and MRI activity were low. Comparing patients who transitioned from interferon-β (IFN), glatiramer acetate (GA), or natalizumab (NTZ), patients previously on NTZ had higher rates of relapse than those previously on GA (annualized relapse rate p = 0.039, percent relapse p = 0.021). Grade III lymphopenia developed in 11% of patients. Lymphopenia was associated with older age ( p < 0.001) and longer disease duration ( p < 0.001). Conclusion: Given the high rates of lymphopenia and discontinuation, it has become our clinical practice to more closely scrutinize older patients and those with a longer disease duration who are potential candidates for initiating DMF therapy.

scholarly journals Correlation Between Disability Measure and Black Hole (T1 Hypointense Lesion) Lesion Load in Brain Magnetic Resonance Imaging (MRI) of Patients With Multiple Sclerosis (MS): Protocol for a Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Amir Valizadeh ◽  
Elham Barati ◽  
Mohammad Ali Sahraian ◽  
Mohammad Reza Fattahi ◽  
Mana Moassefi
Keyword(s):  
Multiple Sclerosis ◽  
Meta Analysis ◽  
Rank Correlation ◽  
Brain Magnetic Resonance Imaging ◽  
Lesion Volume ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient ◽  
Disability Status ◽  
Formation And Evolution ◽  
Magnetic Resonance Imaging Mri

Abstract Introduction: As the role of neurodegeneration in the pathophysiology of multiple sclerosis (MS) has become more prominent, the formation and evolution of chronic or persistent T1-hypointense lesions (Black Holes) have been used as markers of axonal loss and neuronal destruction to measure disease activity. However, findings regarding this subject are controversial. In this study we aim to clarify the level of importance of T1 hypointense lesions for estimating the prognosis of patients.Methods: We will search MEDLINE (through PubMed), Embase and Web of Science for relevant studies. We will extract the Spearman's rank correlation coefficient (SRCC) between the T1 hypointense lesion volume and Extended Disability Status Scale (EDSS) in participants. All included studies will be evaluated for the risk of bias. We will also perform a meta-analysis on the data. The risk of publication bias will be evaluated using Funnel plots. Finally, we will assess the confidence in cumulative evidence using an adapted version of GRADE.

scholarly journals Short-term outcomes of pediatric multiple sclerosis patients treated with alemtuzumab at a Canadian University multiple sclerosis clinic

2020 ◽  
Vol 6 (2) ◽  
pp. 205521732092661
Author(s):  
David Jure Hunt ◽  
Anthony Traboulsee
Keyword(s):  
Multiple Sclerosis ◽  
Stable Disease ◽  
Expanded Disability Status Scale ◽  
Short Term ◽  
Pediatric Multiple Sclerosis ◽  
Risks And Benefits ◽  
Disability Status ◽  
Infusion Reactions ◽  
Multiple Sclerosis Patients

There is a lack of literature documenting the use of alemtuzumab in pediatric multiple sclerosis (MS) patients. Here we describe a 16-year-old and a 17-year-old patient receiving alemtuzumab and being followed for 37 months and 20 months, respectively. Both patients experienced a 1.0 decrease in Expanded Disability Status Scale since initial alemtuzumab infusion and had stable disease. No serious infusion reactions, infections, or definite relapses were recorded on follow-up. Alemtuzumab has been relatively well-tolerated and effective; however, larger, longer-term studies are necessary to understand the specific risks and benefits of alemtuzumab in pediatric MS.

Does MRI lesion activity regress in secondary progressive multiple sclerosis?

2010 ◽  
Vol 16 (4) ◽  
pp. 434-442 ◽  
Author(s):  
Y. Zhao ◽  
AJ Petkau ◽  
A. Traboulsee ◽  
A. Riddehough ◽  
DKB Li
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Short Term ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri ◽  
Short Term Trend

Background: The rate of new contrast-enhancing lesions (CELs) on monthly magnetic resonance imaging (MRI) scans has been shown to decrease over a 9-month period in placebo-treated patients with relapsing—remitting (RR) multiple sclerosis (RRMS). Objective: We examined this phenomenon in placebo-treated secondary progressive MS (SPMS) patients. Methods: Patients were chosen from two clinical trials. Monthly scans were taken at screening, baseline and months 1—9 for Cohort-1 and months 1—6 for Cohort-2. We examined the monthly new CEL rates according to initial CEL level: 0, 1—3, >3 CELs at screening, and presence and absence of pre-study relapses. Results: Respectively, 59, 21 and 14 of the 94 Cohort-1 patients, and 36, 17 and 9 of the 62 Cohort-2 patients had 0, 1—3 and >3 initial CELs. For Cohort-1, the monthly new CEL rates did not change during follow-up, regardless of initial CEL level. For Cohort-2, the monthly rate was unchanged in the 0 initial CEL subgroup, but decreased 33% (95% confidence interval: 8%, 52%) from months 1—3 to months 4—6 in the other two subgroups. For the combined cohorts, a decreasing rate was observed in the 12 patients with >3 initial CELs and pre-study relapses. Conclusions: The short-term trend of new CEL activity in placebo-treated SPMS patients may vary across cohorts.

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