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 Effect of tobacco use on disease activity and DMT discontinuation in multiple sclerosis patients treated with dimethyl fumarate or fingolimod

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732095981
Author(s):  
Carrie M Hersh ◽  
Haleigh Harris ◽  
Malissa Ayers ◽  
Devon Conway
Keyword(s):  
Multiple Sclerosis ◽  
Risk Factor ◽  
Clinical Practice ◽  
Disease Activity ◽  
Tobacco Use ◽  
Dimethyl Fumarate ◽  
Tobacco Exposure ◽  
Disease Modifying Therapy ◽  
Patient Reported ◽  
Multiple Sclerosis Patients

Background Tobacco exposure is a modifiable risk factor for multiple sclerosis (MS). Studies evaluating the relationship between tobacco, disease activity, and disease modifying therapy (DMT) persistence yielded conflicting results. We sought to address this issue with data from clinical practice. Objective To compare 24-month disease outcomes in tobacco versus non-tobacco users treated with dimethyl fumarate (DMF) or fingolimod (FTY) in clinical practice. Methods We retrospectively identified 659 MS patients treated with DMF or FTY, stratified by patient-reported tobacco use. DMT discontinuation and measures of disease activity at 24 months were assessed using propensity score (PS) weighting. Outcome estimates were calculated as tobacco vs non-tobacco use. Results 164 tobacco users (DMF n = 101; FTY n = 63) and 495 non-tobacco users (DMF n = 294; FTY n = 201) were identified. Tobacco (39.4%) and non-tobacco (34.4%) users were equally likely to discontinue DMT (OR = 1.17, 95% CI 0.79, 1.75), but tobacco users discontinued therapy earlier (HR = 1.53, 95% CI 1.06, 2.43). There were no differences in ARR (rate ratio = 1.39, 95% CI 0.97, 1.96). However, tobacco users had decreased odds of NEDA-2 (OR = 0.61, 95% CI 0.44, 0.83). Conclusion Our findings suggest that tobacco is a negative risk factor for inflammatory disease activity and earlier DMF and FTY discontinuation.

Extracranial venous stenosis is an unlikely cause of multiple sclerosis

2010 ◽  
Vol 16 (11) ◽  
pp. 1341-1348 ◽  
Author(s):  
Bassem Yamout ◽  
Aline Herlopian ◽  
Zeinab Issa ◽  
Robert H Habib ◽  
Ahmad Fawaz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Duration ◽  
Disease Onset ◽  
Clear Correlation ◽  
Clinical Relapse ◽  
Venous Stenosis ◽  
Relapsing Remitting ◽  
Similar Disease ◽  
Magnetic Resonance Imaging Mri ◽  
Secondary Phenomenon

Background: Extracranial venous stenosis (EVS) has recently been implicated as the primary cause of multiple sclerosis (MS). Objective: The aim of this study was to determine the presence of EVS in MS patients. Methods: We performed selective extracranial venography on 42 patients with early MS (EMS): clinically isolated syndrome (CIS) or relapsing—remitting MS (RRMS) of less than 5 years duration, and late MS (LMS): RRMS of more than 10 years duration. Magnetic resonance imaging (MRI) and clinical relapse data were reviewed for all patients with EVS. Results: EVS was present in 7/29 patients with EMS and 12/13 patients with LMS, a highly significant statistical difference ( p< 0.001). Only 3/42 patients (all in the LMS group) had two vessel stenoses, while the rest had only one vessel involved. EVS was seen in 1/11 patients with CIS compared with 6/18 RRMS patients of less than 5 years duration. Disease duration was greater in patients with EVS overall ( p < 0.005). LMS remained an independent predictor of EVS following multivariate adjustment for gender, age at disease onset and Expanded Disability Status Scale (EDSS) (Adjusted Odds Ratio = 29 (3—298); p = 0.005]. Within the EMS group, patients with ( n = 7) and without ( n = 22) EVS had similar EDSS and disease duration, suggesting similar disease severity. No clear correlation could be found between site of EVS and anatomic localization of either clinical relapses or MRI gadolinium-enhancing lesions. Conclusions: We conclude that EVS is an unlikely cause of MS since it is not present in most patients early in the disease and rarely involves more than one extracranial vein. It is likely to be a late secondary phenomenon.

scholarly journals Gadopentetate but not gadobutrol accumulates in the dentate nucleus of multiple sclerosis patients

2016 ◽  
Vol 23 (7) ◽  
pp. 963-972 ◽  
Author(s):  
Ludwig Schlemm ◽  
Claudia Chien ◽  
Judith Bellmann-Strobl ◽  
Jan Dörr ◽  
Jens Wuerfel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Dentate Nucleus ◽  
Alternative Explanation ◽  
Disease Duration ◽  
Gadopentetate Dimeglumine ◽  
Progressive Neurodegeneration ◽  
Magnetic Resonance Imaging Mri ◽  
T1 Hyperintensity ◽  
Multiple Sclerosis Patients

Background: Previous studies have postulated an association between dentate nucleus T1 hyperintensity and multiple sclerosis (MS)-related progressive neurodegeneration. Therefore, MS patients have been excluded from most studies investigating brain deposition of gadolinium-based contrast agents (GBCAs). Objective: To study the hypothesis that dentate nucleus T1 hyperintensity in MS patients is associated with GBCA administration. Methods: In a cohort of 97 MS patients, the dentate-to-pons signal intensity ratio (DPSIR) was calculated for 265 consecutive T1-weighted magnetic resonance (MR) scans (including sessions with and without the administration of GBCA). Patients exclusively received either gadopentetate dimeglumine (Gd-DTPA, linear) or gadobutrol (Gd-BT-DO3A, macrocyclic). Results: In patients receiving Gd-DTPA, DPSIR increased significantly between the first and the last scan (+0.009, p < 0.001), and following magnetic resonance imaging (MRI) with Gd-DTPA administration as compared to following an MRI without Gd-DTPA administration (+0.005 vs −0.001; p = 0.022). Additionally, there was a positive linear relationship between the number of Gd-DTPA administrations and the increase in DPSIR ( p = 0.017). No DPSIR increase was observed after Gd-BT-DO3A administration. Conclusion: Dentate nucleus T1 hyperintensity in MS patients is associated with Gd-DTPA (but not Gd-BT-DO3A) administration, suggesting an alternative explanation for the association of T1 hyperintensity with disease duration and severity.

Real-world patient characteristics, treatment patterns and costs in relapsing multiple sclerosis patients treated with glatiramer acetate, dimethyl fumarate or teriflunomide in Germany

2021 ◽  
Author(s):  
Tjalf Ziemssen ◽  
Anna Kurzeja ◽  
Bogdan Muresan ◽  
Jennifer S Haas ◽  
Jessica Alexander ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Patient Characteristics ◽  
Dimethyl Fumarate ◽  
Healthcare Resource Utilization ◽  
Disease Modifying Therapies ◽  
High Adherence ◽  
Treatment Naïve ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Aim: To evaluate adherence, healthcare resource utilization (HRU) and costs for glatiramer acetate (GA; injectable), dimethyl fumarate (oral) and teriflunomide (oral) in relapsing multiple sclerosis. Patients & methods: Retrospective analyses of a claims database. Results: Teriflunomide patients were older with more co-morbidities and fewer relapses versus GA and dimethyl fumarate. GA patients were mostly disease-modifying therapies (DMTs)-treatment naive. Treatment adherence was 61–70%. All DMTs reduced HRU versus pre-index. Costs were comparable across cohorts. High adherence reduced hospitalizations and several costs versus low adherers. Conclusion: Adherence rates were high and comparable with all DMTs. Similar (and high) reductions in HRU and costs occurred with all DMTs. High adherence improved economic outcomes versus low adherence. Thus, investing in adherence improvement is beneficial to improve outcomes in relapsing multiple sclerosis.

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 Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis

2021 ◽  
Author(s):  
Matteo Lucchini ◽  
Luca Prosperini ◽  
Maria Chiara Buscarinu ◽  
Diego Centonze ◽  
Antonella Conte ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Lymphocyte Count ◽  
Disease Duration ◽  
Dimethyl Fumarate ◽  
Oral Drug ◽  
Delayed Initiation ◽  
Grade Ii ◽  
Relapsing Multiple Sclerosis ◽  
Grade Iii ◽  
Count Recovery

Abstract Background Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5–10% DMF-treated patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce. Objectives To characterize ALC recovery and to identify predictors of slower recovery after DMF interruption. Methods Multicenter data from RMS patients who started DMF and developed lymphopenia during treatment were collected. In patients with grade II–III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm3. Results Among 1034 patients who started DMF, we found 198 (19.1%) patients with lymphopenia and 65 patients (6.3%) who discontinued DMF due to persistent grade II–III lymphopenia. Complete data were available for 51 patients. All patients recovered to ALC > 800 cells/mm3 with a median time of 3.4 months. Lower ALCs at DMF suspension (HR 0.98; p = 0.005), longer disease duration (HR 1.29; p = 0.014) and prior exposure to MS treatments (HR 0.03; p = 0.025) were found predictive of delayed ALC recovery. Conclusion ALC recovery after DMF withdrawal is usually rapid, nevertheless it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy.

scholarly journals Progressive multifocal leukoencephalopathy in dimethyl fumarate-treated multiple sclerosis patients

2020 ◽  
pp. 135245852094915 ◽  
Author(s):  
Allison LM Jordan ◽  
Jennifer Yang ◽  
Caitlyn J Fisher ◽  
Michael K Racke ◽  
Yang Mao-Draayer
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Immune Cell ◽  
Dimethyl Fumarate ◽  
The Central Nervous System ◽  
Immune Cell Migration ◽  
Absolute Lymphocyte Counts ◽  
Adhesive Molecules ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Dimethyl fumarate (DMF), a fumaric acid with antioxidant and immunomodulatory properties, is among the most commonly used oral therapies for relapsing multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) has been associated with several disease-modifying therapies (DMTs), including DMF in treating MS. We present detailed clinical characteristics of nine PML cases and show that the PML incidence in DMF-treated patients is 0.02 per 1000 patients. In addition to persistent severe lymphopenia, older age appears to be a potential risk for PML. However, younger patients without lymphopenia were also observed to develop PML. DMF-associated PML has occurred in patients with absolute lymphocyte counts (ALCs) above the guideline threshold, suggesting that changes in specific subsets might be more important than total ALC. Furthermore, since DMF has been found to decrease immune cell migration by decreasing the expression of adhesive molecules, the cerebrospinal fluid (CSF) immune profile may also be useful for assessing PML risk in DMF-treated patients. This review provides an up-to-date assessment of PML cases occurring in DMF-treated patients and discusses other potential considerations in light of our current understanding of DMF’s mechanism of action on the immune system in the periphery and in the central nervous system (CNS).

Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis

2017 ◽  
Vol 24 (3) ◽  
pp. 245-255 ◽  
Author(s):  
Gianluigi Mancardi ◽  
Maria Pia Sormani ◽  
Paolo A Muraro ◽  
Giacomo Boffa ◽  
Riccardo Saccardi
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Haematopoietic Stem Cell Transplantation ◽  
Haematopoietic Stem Cell ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis ◽  
Related Mortality

In the majority of relapsing multiple sclerosis patients, the disease can be quite easily controlled by already available, approved therapies. There are, however, some aggressive cases who continue to have clinical and magnetic resonance imaging (MRI) activity in spite of the treatment. These are the cases who may now receive benefit from intense immunosuppression followed by autologous haematopoietic stem cell transplantation (aHSCT). In this review, we describe the method and the rationale of aHSCT, the more recently published studies that demonstrate its efficacy in selected multiple sclerosis cases, the problems related to safety and the transplant-related mortality risk of the procedure. A description of the ideal patient who can take advantage of aHSCT is outlined and, finally, the ongoing studies which are near to completion or are close to starting are briefly reported.

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