scholarly journals Real-world effectiveness of dimethyl fumarate versus fingolimod in a cohort of patients with multiple sclerosis using standardized, quantitative outcome metrics

2022 ◽  
Vol 8 (1) ◽  
pp. 205521732110698
Author(s):  
Carrie M Hersh ◽  
Arman Altincatal ◽  
Nicholas Belviso ◽  
Shivani Kapadia ◽  
Carl de Moor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sensitivity Analysis ◽  
Real World ◽  
Dimethyl Fumarate ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Brain Volume Loss ◽  
Disability Status ◽  
Magnetic Resonance Imaging Mri

Background Prior studies suggest comparable effectiveness of dimethyl fumarate (DMF) and fingolimod (FTY) in multiple sclerosis (MS) using relapse, Expanded Disability Status Score (EDSS), and magnetic resonance imaging (MRI) lesion metrics. Objective Compare the real-world effectiveness of DMF versus FTY using quantitative, validated neuroperformance tests, MRI, and serum neurofilament light chain (sNfL) outcomes while controlling for between-group differences. Methods Patients were eligible if on DMF or FTY when first enrolled in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network and had ≥1-year follow-up in MS PATHS. Sensitivity analysis included a subgroup who started DMF/FTY ≤2 years from enrolment. After propensity score weighting, differences in means and in mean 1-year change of neuroperformance and MRI outcomes were compared. sNfL levels were assessed. This was a non-randomized comparison. Results In the overall cohort, no significant differences were observed between DMF ( n = 702) and FTY ( n = 600) in neuroperformance or MRI outcomes including brain volume loss; mean time (SD) since treatment initiation was 1.98 (0.68) years for DMF and 2.02 (0.75) years for FTY. A sensitivity analysis controlling for DMF and FTY treatment duration yielded similar results. Conclusion In this study, DMF and FTY demonstrated similar effects on physical and cognitive neuroperformance and MRI outcomes. Direct comparisons to other fumarates and S1P receptor modulators were not conducted.

De-escalating rituximab dose results in stability of clinical, radiological, and serum neurofilament levels in multiple sclerosis

2020 ◽  
pp. 135245852095203
Author(s):  
Giulio Disanto ◽  
Paolo Ripellino ◽  
Gianna C Riccitelli ◽  
Rosaria Sacco ◽  
Barbara Scotti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Comparable Efficacy ◽  
High Dose ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T2 Lesions ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri

Background: Phase II and observational studies support the use of rituximab in multiple sclerosis. Standard protocols are lacking, but studies suggest comparable efficacy between low- and high-dose regimens. Objective: To evaluate effectiveness and safety of de-escalating rituximab dose from 1000 to 500 mg/6 months in multiple sclerosis. Methods: Patients were switched from rituximab 1000 to 500 mg/6 months and prospectively followed for 12 months. Relapses, disability, occurrence of brain/spinal magnetic resonance imaging (MRI) lesions, serum neurofilament light chain (NfL), CD19+ B cell, and IgG concentrations were analyzed. Results: Fifty-nine patients were included (37 relapsing-remitting, 22 secondary progressive). No relapses occurred, with no difference in expanded disability status scale (EDSS) between baseline (4 (2.5–4.5) and 12 months (3.5 (2.5–5.5) p = 0.284). Overall, three new T2 lesions appeared during follow-up. NfL concentration was stable between baseline (7.9 (5.9–45.2) pg/mL) and 12 months (9.1 (5.9–21.3) pg/mL, p = 0.120). IgG concentrations decreased with greater rituximab load (coefficient = −0.439, p = 0.041). IgG deficient patients had greater risk of infections (OR = 6.27, 95% CI = 1.71–22.9, p = 0.005). Conclusion: De-escalating rituximab dose from 1000 to 500 mg/6 months is safe, results in clinical and radiological stability, and does not affect serum NfL over 12 months. Rituximab load negatively influences IgG concentrations, and IgG deficient patients are at higher risk of infections.

scholarly journals Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

2021 ◽  
Vol 14 ◽  
pp. 175628642110576
Author(s):  
Kimberley Allen-Philbey ◽  
Stefania De Trane ◽  
Zhifeng Mao ◽  
Cesar Álvarez-González ◽  
Joela Mathews ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Stage ◽  
Neurofilament Light Chain ◽  
Skin Reactions ◽  
Neurofilament Light ◽  
Disability Status ◽  
Walking Tests ◽  
Grade 3

Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. Methods: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data ( n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data ( n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.

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.

scholarly journals Should We Use Clinical Tools to Identify Disease Progression?

2021 ◽  
Vol 11 ◽  
Author(s):  
Hernan Inojosa ◽  
Undine Proschmann ◽  
Katja Akgün ◽  
Tjalf Ziemssen
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Markers ◽  
Disability Progression ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Secondary Progressive ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Clinical Tools

The presence of disability progression in multiple sclerosis (MS) is an important hallmark for MS patients in the course of their disease. The transition from relapsing remitting (RRMS) to secondary progressive forms of the disease (SPMS) represents a significant change in their quality of life and perception of the disease. It could also be a therapeutic key for opportunities, where approaches different from those in the initial phases of the disease can be adopted. The characterization of structural biomarkers (e.g., magnetic resonance imaging or neurofilament light chain) has been proposed to differentiate between both phenotypes. However, there is no definite threshold between them. Whether the risk of clinical progression can be predicted by structural markers at early disease phases is still a focus of clinical research. However, several theories and pathological evidence suggest that both disease phenotypes are part of a continuum with common pathophysiological mechanisms. In this case, the clinical evaluation of the patients would play a preponderant role above destruction biomarkers for the early identification of disability progression and SPMS. For this purpose, the use of clinical tools beyond the Expanded Disability Status Scale (EDSS) should be considered. Besides established functional tests such as the Multiple Sclerosis Functional Composite (MSFC), patient's neurological history or digital resources may help neurologists in the decision-taking. In this article, we discuss arguments for the use of clinical markers in the detection of secondary progressive MS and the characterization of progressive disease activity.

Comparison of rituximab originator (MabThera®) to biosimilar (Truxima®) in patients with multiple sclerosis

2020 ◽  
pp. 135245852091217 ◽  
Author(s):  
Thomas Perez ◽  
Audrey Rico ◽  
Clémence Boutière ◽  
Adil Maarouf ◽  
Marjorie Roudot ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Efficacy And Safety ◽  
Middle Income ◽  
Middle Income Countries ◽  
Disability Status ◽  
Baseline Characteristics ◽  
Magnetic Resonance Imaging Mri ◽  
Improve Access

Background: Rituximab’s originator MabThera® or Rituxan® has demonstrated high efficacy in multiple sclerosis (MS). Because of the patent expiration, rituximab biosimilars have been developed. However, because a biosimilar is not the exact copy of the originator, the efficacy and safety of a biosimilar may significantly differ. Objectives: To compare the efficacy and safety of the biosimilar Truxima® and the originator MabThera® in MS. Methods: Consecutive MS patients receiving MabThera® or Truxima® were prospectively followed during 1 year after treatment introduction. Allocation to each treatment depended on the period of introduction and not the physician’s choice. Lymphocyte count, clinical and magnetic resonance imaging (MRI) activity, Expanded Disability Status Scale (EDSS), and adverse events were compared. Results: In total, 105 and 40 patients received MabThera® and Truxima®, respectively. The two groups did not differ in baseline characteristics. Effect on CD19+ lymphocytes and disease activity were similar during follow-up. EDSS remained stable, with no difference between groups. Adverse events were similar between groups. Conclusion: The efficacy and safety of the rituximab biosimilar Truxima® seem equivalent to the originator MabThera® in MS patients. Truxima® could represent a relatively cheap and safe therapeutic alternative to MabThera® and could improve access to highly efficient therapy for MS in low- or middle-income countries.

Characterizing cognitive function during relapse in multiple sclerosis

2014 ◽  
Vol 20 (13) ◽  
pp. 1745-1752 ◽  
Author(s):  
Ralph HB Benedict ◽  
Sarah Morrow ◽  
Jonathan Rodgers ◽  
David Hojnacki ◽  
Margaret A Bucello ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Test Performance ◽  
Clinical Status ◽  
Cognitive Change ◽  
Expanded Disability Status Scale ◽  
Resonance Imaging ◽  
Disability Status ◽  
Magnetic Resonance Imaging Mri ◽  
Meaningful Event

Objective: To characterize neuropsychological (NP) test performance during multiple sclerosis (MS) relapse and recovery. Methods: Clinical status was assessed with NP testing and Expanded Disability Status Scale (EDSS) in 24 relapsing patients, and 24 individually-matched, stable controls. All presented with cognitive symptoms as indicated by patient, clinician or caregiver perceived decline, but were free of optic neuritis, ataxia and upper extremity weakness that could compromise NP testing. The presence of enhancing magnetic resonance imaging (MRI) lesions was considered confirmatory of relapse. Relapsing patients were treated with corticosteroids. NP testing and EDSS were compared to pre-relapse baseline levels, and three-month, post-relapse, follow-up. Results: Analyses revealed significant decline on the Symbol Digit Modalities Test (SDMT) ( p=0.005) and worsening on EDSS ( p=0.019). Impairment was observed at the point of relapse in cases but not controls. The groups were no longer different at three-month follow-up. The increment of decline on SDMT was 3.5 raw score points, or roughly 6%. Conclusions: This is the first study to assess NP status changes during MS relapse using well established, reliable metrics. The presence of a clinically meaningful event is substantiated by decline in NP testing, observed or reported cognitive change, and in a subset of patients, gadolinium-enhancing MRI lesions.

scholarly journals Comparative effectiveness of teriflunomide and dimethyl fumarate

Neurology ◽  
2019 ◽  
Vol 92 (16) ◽  
pp. e1811-e1820 ◽  
Author(s):  
Mathias Due Buron ◽  
Thor Ameri Chalmer ◽  
Finn Sellebjerg ◽  
Jette Frederiksen ◽  
Monika Katarzyna Góra ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Efficacy ◽  
Dimethyl Fumarate ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo compare on-treatment efficacy and discontinuation outcomes in teriflunomide (TFL) and dimethyl fumarate (DMF) in the treatment of relapsing-remitting multiple sclerosis (RRMS) in a real-world setting.MethodsWe identified all patients starting TFL or DMF from the Danish Multiple Sclerosis Registry and compared on-treatment efficacy outcomes between DMF using TFL, adjusted for clinical baseline variables and propensity score-based methods.ResultsWe included 2,236 patients in the study: 1,469 patients on TFL and 767 on DMF. Annualized relapse rates (ARRs) in TFL and DMF were 0.16 (95% confidence interval [CI] 0.13–0.20) and 0.09 (95% CI 0.07–0.12), respectively. Relapse rate ratio for DMF/TFL was 0.58 (95% CI 0.46–0.73, p < 0.001). DMF had a higher relapse-free survival proportion at 48 months of follow-up (p < 0.05). We observed no difference in Expanded Disability Status Scale score worsening. Discontinuations due to disease breakthrough were 10.2% (95% CI 7.6%–12.8%) and 22.1% (95% CI 19.2%–25.0%) for DMF and TFL, respectively. A subgroup analysis of ARRs in 708 patients with available baseline MRI T2 lesion amount reported similar results after adjustment.ConclusionWe found lower ARR, higher relapse-free survival, and lower incidence of discontinuation due to disease breakthrough on treatment with DMF compared with TFL.Classification of evidenceThis study provides Class II evidence that for patients with RRMS, DMF is more effective in preventing relapses and has lower discontinuation due to disease breakthrough compared with TFL.

scholarly journals Tetravalent Influenza Vaccine Is Not Associated With Neuroaxonal Damage in Multiple Sclerosis Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Tobias Moser ◽  
Michael Seiberl ◽  
Julia Feige ◽  
Lara Bieler ◽  
Richard F. Radlberger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Influenza Vaccine ◽  
Fold Increase ◽  
Dimethyl Fumarate ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Humoral Immune ◽  
Antibody Titers ◽  
Disease Reactivation ◽  
Multiple Sclerosis Patients

BackgroundEfficacy of vaccines and disease activity linked to immunization are major concerns among people with multiple sclerosis (pwMS).ObjectiveTo assess antibody responses to seasonal influenza antigens and vaccine-associated neuroaxonal damage utilizing serum neurofilament light chain (sNfL) in pwMS receiving dimethyl fumarate (DMF).MethodsIn this prospective study, the 2020/2021 seasonal tetravalent influenza vaccine was administered to 20 pwMS treated with DMF and 15 healthy controls (HCs). The primary endpoints were responder rate of strain-specific antibody production (seroconversion or significant (4-fold) increase in influenza-antibody titers for ≥2/4 strains) at 30 days post-vaccination and changes in sNfL levels.ResultsAll patients treated with DMF fulfilled the responder criteria for immunization compared with 53% of the controls. However, higher proportions of HCs already had influenza-antibody titers ≥1:40 at baseline (53% vs. 41%, p = 0.174). sNfL levels were comparable among both groups at baseline and did not increase 34 days after vaccination. In addition, no clinical or radiological disease reactivation was found.ConclusionDMF-treated patients mount an adequate humoral immune response to influenza vaccines. Within the limits of the small cohort investigated, our data suggest that influenza immunization is not associated with clinical or subclinical disease reactivation.

Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis

2018 ◽  
Vol 25 (5) ◽  
pp. 678-686 ◽  
Author(s):  
Nelly Siller ◽  
Jens Kuhle ◽  
Muthuraman Muthuraman ◽  
Christian Barro ◽  
Timo Uphaus ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Single Molecule ◽  
Light Chain ◽  
Neuronal Damage ◽  
Axonal Damage ◽  
Lesion Volume ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Magnetic Resonance Imaging Mri ◽  
Brain Parenchymal

Background: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament – a major component of the neuro-axonal cytoskeleton – is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. Objective: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. Methods: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology. Standardized 3 T magnetic resonance imaging (MRI) was performed at baseline and 1–3 consecutive follow-ups (42 patients; range: 6–37 months). Results: Baseline sNfL correlated significantly with T2 lesion volume ( r = 0.555, p < 0.0001). There was no correlation between baseline sNfL and age, Expanded Disability Status Scale (EDSS) score or other calculated MRI measures. However, T2 lesion volume increased ( r = 0.67, p < 0.0001) and brain parenchymal volume decreased more rapidly in patients with higher baseline sNfL ( r = −0.623, p = 0.0004). Gd-enhancing lesions correlated positively with sNfL levels. Initiation of disease-modifying treatment led to a significant decrease in sNfL levels. Conclusion: sNfL indicates acute inflammation as demonstrated by correlation with Gd+ lesions. It is a promising biomarker for neuro-axonal damage in early multiple sclerosis (MS) patients, since higher baseline sNfL levels predicted future brain atrophy within 2 years.

scholarly journals Autologous Haematopoietic Stem Cell Transplantation in Active Multiple Sclerosis: a Real-world Case Series

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012449
Author(s):  
Richard S Nicholas ◽  
Elijah Edward Rhone ◽  
Alice Mariottini ◽  
Eli Silber ◽  
Omar Malik ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Real World ◽  
Haematopoietic Stem Cell ◽  
Expanded Disability Status Scale ◽  
Free Survival ◽  
Disability Status

Objective:to examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting.Methods:retrospective cohort study on PwMS treated with AHSCT at two centers in London, UK, consecutively between 2012 and 2019 who had ≥ 6 months of follow-up or died at any time. Primary outcomes were survival free of MS relapses, MRI new lesions and worsening of expanded disability status scale (EDSS). Adverse events rates were also examined.Results:the cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS (RRMS). At baseline, the median expanded disability status scale (EDSS) was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6–85). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of subjects at 2 years and 85% at 4 years. EDSS progression-free survival (PFS) was 75% at 2 years and 65% at 4 years. EBV reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplant-related deaths within 100 days (2.5%), all following fluid overload and cardiac or respiratory failure.Conclusions:efficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher.Classification of evidence:this study is rated Class IV because of the uncontrolled, open-label design.

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