Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study

Background: With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences. Objectives: To identify prognostic factors for early switch after first therapy choice. Methods: Newly diagnosed relapsing–remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models. Results: We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p < 0.001), dimethyl-fumarate (HR = 0.60; p = 0.037), teriflunomide (HR = 0.21; p = 0.031) as compared to interferons. Younger age (HR = 0.96; p < 0.001), diagnosis delay (HR = 1.23; p = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17; p = 0.001), and spinal cord lesions (HR = 1.46; p = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61; p = 0.001), fingolimod (HR = 0.35; p = 0.002), and dimethyl-fumarate (HR = 0.57; p = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43; p = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28; p = 0.047). Conclusion: Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.

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Lymphocytes subsets after one year of dimethylfumarate treatment in multiple sclerosis: a real life study

10.26226/morressier.59a3e8b6d462b8028d8951d7 ◽

2017 ◽

Author(s):

Sara La Gioia

Keyword(s):

Multiple Sclerosis ◽

Real Life ◽

Life Study ◽

Real Life Study ◽

One Year ◽

Lymphocytes Subsets

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Efficacy and discontinuation of nabiximols in patients with multiple sclerosis: a real-life study

10.26226/morressier.5b719e475aff74008ae4caaa ◽

2018 ◽

Author(s):

Valeria Bergamaschi ◽

Valeria ['Brichetto']

Keyword(s):

Multiple Sclerosis ◽

Real Life ◽

Life Study ◽

Real Life Study

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Clinical predictors of Dimethyl Fumarate response in multiple sclerosis: a real life multicentre study

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2019.101871 ◽

2020 ◽

Vol 38 ◽

pp. 101871 ◽

Cited By ~ 4

Author(s):

R. Lanzillo ◽

M. Moccia ◽

R. Palladino ◽

E. Signoriello ◽

A. Carotenuto ◽

...

Keyword(s):

Multiple Sclerosis ◽

Multicentre Study ◽

Real Life ◽

Dimethyl Fumarate ◽

Clinical Predictors

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CD56bright Natural Killer Cells: A Possible Biomarker of Different Treatments in Multiple Sclerosis

Journal of Clinical Medicine ◽

10.3390/jcm9051450 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1450 ◽

Cited By ~ 1

Author(s):

Alice Laroni ◽

Antonio Uccelli

Keyword(s):

Multiple Sclerosis ◽

Nk Cells ◽

Natural Killer ◽

Dimethyl Fumarate ◽

Regulatory Function ◽

Clinical Activity ◽

Hematopoietic Stem ◽

Immune Mediated ◽

The Central Nervous System ◽

Magnetic Resonance Imaging Mri

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system, which leads, in many cases, to irreversible disability. More than 15 disease-modifying treatments (DMTs) are available for the treatment of MS. Clinical activity or activity at magnetic resonance imaging (MRI) are now used to assess the efficacy of DMTs, but are negative prognostic factors per se. Therefore, a biomarker permitting us to identify patients who respond to treatment before they develop clinical/radiological signs of MS activity would be of high importance. The number of circulating CD56bright natural killer (NK) cells may be such a biomarker. CD56bright NK cells are a regulatory immune population belonging to the innate immune system. The number of CD56bright NK cells increases upon treatment with interferon-beta, alemtuzumab, dimethyl fumarate, after autologous hematopoietic stem cell transplantation, and is higher in those who respond to fingolimod. In some cases, an increased number of CD56bright NK cells is associated with an increase in their regulatory function. In the current review, we will evaluate the known effect on CD56bright NK cells of DMTs for MS, and will discuss their possible role as a biomarker for treatment response in MS.

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Efficacy and safety of delayed-release dimethyl fumarate in treatment-naïve Japanese patients with relapsing-remitting multiple sclerosis: A post-hoc subgroup analysis of the apex study

Journal of the Neurological Sciences ◽

10.1016/j.jns.2017.08.2241 ◽

2017 ◽

Vol 381 ◽

pp. 795-796

Author(s):

M. Mori ◽

T. Ohashi ◽

Y. Onizuka ◽

K. Hiramatsu ◽

M. Hase ◽

...

Keyword(s):

Multiple Sclerosis ◽

Subgroup Analysis ◽

Japanese Patients ◽

Dimethyl Fumarate ◽

Efficacy And Safety ◽

Relapsing Remitting ◽

Treatment Naïve ◽

Remitting Multiple Sclerosis ◽

Post Hoc ◽

Relapsing Remitting Multiple Sclerosis

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

Multiple Sclerosis Journal ◽

10.1177/1352458517709956 ◽

2017 ◽

Vol 24 (7) ◽

pp. 942-950 ◽

Cited By ~ 12

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.

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Successful pregnancy after natalizumab-associated progressive multifocal leukoencephalopathy in a patient with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458516678475 ◽

2016 ◽

Vol 23 (3) ◽

pp. 483-486 ◽

Cited By ~ 3

Author(s):

Kalliopi Pitarokoili ◽

Kerstin Hellwig ◽

Carsten Lukas ◽

Ralf Gold

Keyword(s):

Multiple Sclerosis ◽

Progressive Multifocal Leukoencephalopathy ◽

Clinical Presentation ◽

Dimethyl Fumarate ◽

Resonance Imaging ◽

Successful Pregnancy ◽

Uncomplicated Pregnancy ◽

Pregnancy And Delivery ◽

Magnetic Resonance Imaging Mri ◽

Inflammatory Syndrome

We report the case of a post-progressive multifocal leukoencephalopathy (PML), multiple sclerosis (MS) patient with an uncomplicated pregnancy and delivery. A 28-year-old woman on natalizumab (total of 49 infusions) was diagnosed with PML due to typical magnetic resonance imaging (MRI) and clinical presentation. John Cunningham virus (JCV) was detected in the cerebrospinal fluid (CSF) during the immune reconstitution inflammatory syndrome (IRIS). Nine months after PML onset, JCV negativity in the CSF was observed. MS was stabilised with dimethyl fumarate (DMF), and 18 months later, a desired pregnancy was reported, resulting in the birth of a healthy boy. Our report gives new hope regarding family planning for post-PML patients.

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A comparison of multiple sclerosis clinical disease activity between patients treated with natalizumab and fingolimod

Multiple Sclerosis Journal ◽

10.1177/1352458516643393 ◽

2016 ◽

Vol 23 (2) ◽

pp. 234-241 ◽

Cited By ~ 25

Author(s):

Nils Koch-Henriksen ◽

Melinda Magyari ◽

Finn Sellebjerg ◽

Per Soelberg Sørensen

Keyword(s):

Multiple Sclerosis ◽

Propensity Score ◽

Disease Activity ◽

Propensity Score Matching ◽

Relapse Rate ◽

Real Life ◽

Clinical Disease ◽

Clinical Disease Activity ◽

Magnetic Resonance Imaging Mri ◽

Treatment Register

Background: Natalizumab and fingolimod were approved for treatment of active relapsing-remitting multiple sclerosis (RRMS) in Denmark in 2006 and 2011, respectively. There have been no randomized head-to-head studies comparing the two drugs. Objective: To compare the clinical efficacy of natalizumab and fingolimod. Methods: Data on all Danish RRMS patients who started their first second-line treatment with natalizumab or fingolimod from July 2011 to March 2015 were prospectively recorded in the Danish Multiple Sclerosis (MS) Treatment Register. The two treatment arms were 1:1 propensity score matched by baseline covariates using ‘nearest neighbour’ method. Results: Propensity score matching left 928 of 1309 RRMS cases, 464 in each treatment group. The on-treatment annualized relapse rate was 0.296 (95% confidence interval (CI): 0.26–0.34) for natalizumab and 0.307 (95% CI: 0.27–0.35) for fingolimod. The adjusted relapse rate ratio was 0.93 (95% CI: 0.74–1.17; p = 0.53). Mean time to first relapse was 2.55 and 2.56 years, respectively ( p = 0.76). There was no difference in change of Expanded Disability Status Scale (EDSS). Conclusion: We found no differences in clinical disease activity between natalizumab- and fingolimod-treated RRMS patients in this real-life observational study. However, the lack of magnetic resonance imaging (MRI) data for the propensity score matching may conceal a higher efficacy of natalizumab.

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Comparative effectiveness of dimethyl fumarate in Multiple Sclerosis

10.21203/rs.3.rs-321622/v1 ◽

2021 ◽

Author(s):

Pauline Bosco-Levy ◽

Marc Debouverie ◽

Bruno Brochet ◽

Céline Louapre ◽

Elisabeth Maillard ◽

...

Keyword(s):

Multiple Sclerosis ◽

Negative Binomial ◽

Real Life ◽

Logistic Models ◽

Negative Binomial Regression ◽

Dimethyl Fumarate ◽

Population Based ◽

Disability Progression ◽

Real Life Setting ◽

Using Data

Abstract Objectives: To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse (ARR) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real life setting. Methods: A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between July 1, 2015 and December 12, 2017, with 4.5 years of database history and 1 to 3.5 years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional Propensity Score. Negative binomial regression and a regression logistic models were used to estimate the relative risk (RR ± [95% CI]) of ARR and the Odds Ratio (OR ± [95% CI]) of disability progression, respectively. Results: Overall, 9 304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF- IMM, patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARR compared to IMM (RR 0.72 [0.61 - 0.86]) and TERI (0.81 [0.68 - 0.96]). The risk of the progression of MS specific disability was not significantly different for any matched cohorts.Interpretation: DMF is associated with lower risk of relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM).

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