Real-world effectiveness of natalizumab treatment in patients with relapsing multiple sclerosis in Argentina and Chile

ABSTRACT Background: The real-world effectiveness of natalizumab in people with relapsing multiple sclerosis (PwRMS) in Argentina and Chile has not been reported. Objective: To evaluate the effectiveness of natalizumab treatment in PwRMS in Argentina and Chile, in clinical practice. Methods: We conducted a multicenter retrospective and observational study. We reviewed the medical records of PwRMS who had been treated with natalizumab for at least one year, without any interruption in MS treatment that lasted more than 12 weeks. We analyzed changes in annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score and magnetic resonance imaging (MRI). Results: We enrolled 117 PwRMS treated with natalizumab. Natalizumab treatment was associated with a significant reduction in ARR from baseline after one year and two years of treatment (from 1.97 to 0.06 and 0.09 respectively; p<0.01 at each time point). From baseline, EDSS scores were reduced by 0.71 and 0.73 points at one and two years, respectively (p<0.01). No worsening of disability was observed in 82.9 and 67.5% of PwRMS at one and two years, respectively. The improvement in disability was 44.4% at one year and 39.3% at two years. During natalizumab treatment, the number of relapse-related hospitalizations was significantly reduced (p<0.01). MRI lesions (new/enlarging T2 or gadolinium-enhancing) were significantly reduced, compared with baseline. No evidence of disease activity was observed in 65% at two years of natalizumab treatment. Conclusions: Natalizumab significantly reduced disease activity in PwRMS in Argentina and Chile, in clinical practice. Natalizumab also decreased the number of hospitalizations compared with pre-natalizumab treatment.

Download Full-text

Ocrelizumab in Multiple Sclerosis: A Real-World Study From Spain

Frontiers in Neurology ◽

10.3389/fneur.2020.592304 ◽

2021 ◽

Vol 11 ◽

Author(s):

Angel P. Sempere ◽

Leticia Berenguer-Ruiz ◽

Ines Borrego-Soriano ◽

Amparo Burgos-San Jose ◽

Luis Concepcion-Aramendia ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Practice ◽

Real World ◽

Median Number ◽

Progressive Multiple Sclerosis ◽

Primary Progressive Multiple Sclerosis ◽

Clinical Practice Setting ◽

Number Of Treatment ◽

Relapsing Multiple Sclerosis

Objectives: The aim of this study was to describe the tolerability, safety, and effectiveness of ocrelizumab for primary progressive multiple sclerosis (PPMS) and relapsing multiple sclerosis (RMS) in a clinical practice setting.Methods: In this retrospective observational study, we analyzed clinical and MRI data in all patients with PPMS and RMS who had received at least one infusion of ocrelizumab in two health areas in south-eastern Spain. Patients involved in any ocrelizumab trial and those patients with a follow-up shorter than 6 months were excluded.Results: The cohort included 70 patients (42 women) who had received ocrelizumab; 30% had PPMS and 70%, RMS. At baseline, patients' mean age was 47.1 years in the PPMS group and 39.2 years in the RMS group, while the median EDSS was 3.0 and 2.5, respectively. Median follow-up was 13.6 months. The median number of treatment cycles was three. Most patients remained free from clinical and MRI activity after ocrelizumab initiation. Baseline MRI showed T1 Gd-enhancing lesions in 57% of the patients; by the first MRI control at 4–6 months, all patients except one were free of T1 Gd-enhancing lesions (69/70, 98.6% P < 0.001). The proportion of patients with NEDA was 94% in the group of RMS patients who were followed for at least 1 year. Ocrelizumab was generally well-tolerated; the most common adverse events were infusion-related reactions and infections, none of which were serious.Conclusions: Our real-world study supports the tolerability, safety, and effectiveness of ocrelizumab in clinical practice.

Download Full-text

Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318824618 ◽

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

Download Full-text

Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20150098 ◽

2015 ◽

Vol 73 (9) ◽

pp. 736-740 ◽

Cited By ~ 2

Author(s):

Enedina Maria Lobato de Oliveira ◽

Renata Faria Simm ◽

Gorana Dasic ◽

Marília Mamprim de Morais ◽

Samira Luiza dos Apostolos Perreira ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disability Progression ◽

Neurological Disability ◽

Line Therapy ◽

Disability Status ◽

Natalizumab Treatment ◽

Third Line Therapy ◽

Third Line ◽

One Year ◽

The Impact

Objective Analyze the demographics, clinical characteristics, efficacy and safety of natalizumab treatment in Brazilian patients with multiple sclerosis (MS) followed up for at least 12 months, in two tertiary MS care centers in São Paulo.Method We evaluated the effect of natalizumab treatment on annualized relapse rate and disability progression in 75 patients with MS treated with natalizumab for at least 12 months. A subgroup analysis was performed to evaluate efficacy of natalizumab treatment in patients with Expanded Disability Status Scale (EDSS) ≤ 3.0 vs patients with EDSS > 3.Results Patients treated for at least one year with natalizumab showed a 91% reduction in aRR, as well and an improvement in neurological disability. The impact of natalizumab treatment was greater in patients with EDSS < 3.0. Overall, natalizumab was safe but one patient developed progressive multifocal leukoencephalopathy.Conclusion Natalizumab as a third line therapy is safe and efficacious, especially in patients with mild neurological disability.

Download Full-text

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

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/20552173211069852 ◽

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.

Download Full-text

Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458507085759 ◽

2008 ◽

Vol 14 (5) ◽

pp. 663-670 ◽

Cited By ~ 60

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.

Download Full-text

Time for Change – Evolution of Real-world Evidence Outcome Measures in Multiple Sclerosis Exemplified by Fingolimod

European Neurological Review ◽

10.17925/enr.2014.09.02.136 ◽

2015 ◽

Vol 9 (2) ◽

pp. 136 ◽

Cited By ~ 8

Author(s):

Mefkure Eraksoy ◽

Helmut Butzkueven ◽

Tjalf Ziemssen ◽

Robert Zivadinov ◽

◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Practice ◽

Real World ◽

Imaging Data ◽

Real World Evidence ◽

Number Of Patients ◽

Magnetic Resonance Imaging Mri ◽

Minimum Dataset ◽

Automated Procedures

Real-world evidence provides important information concerning the long-term effectiveness and safety of disease-modifying treatments (DMTs) for multiple sclerosis (MS) in clinical practice in a large number of patients. These data enhance and extend the results from randomised clinical trials and include information that cannot easily be obtained in trials such as treatment efficacy in non-trial populations (e.g. those with co-morbidities, older patients and children) and long-term safety analyses. Such data are compatible with specialist clinical practice and, when accumulated in multicentre databases using an agreed minimum dataset, these data can provide invaluable information on long-term disease progression and treatment. Real-world evidence in terms of fingolimod is reviewed and clearly demonstrates its long-term effectiveness and safety. Currently, imaging data are not systematically collected but the development of improved standard magnetic resonance imaging (MRI) protocols and automated procedures now makes this a realistic option in the near future. Automated (or largely automated) MRI analytics are likely to greatly enhance and further strengthen real-world evidence for outcomes of different treatment algorithms incorporating more sophisticated MRI measures.

Download Full-text

Temporal profile of serum neurofilament light in multiple sclerosis: Implications for patient monitoring

Multiple Sclerosis Journal ◽

10.1177/1352458520972573 ◽

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.

Download Full-text

Personalized B-cell tailored dosing of ocrelizumab in patients with multiple sclerosis during the COVID-19 pandemic

Multiple Sclerosis Journal ◽

10.1177/13524585211028833 ◽

2021 ◽

pp. 135245852110288

Author(s):

Zoë YGJ van Lierop ◽

Alyssa A Toorop ◽

Wouter JC van Ballegoij ◽

Tom BG Olde Dubbelink ◽

Eva MM Strijbis ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

B Cell ◽

Cell Count ◽

Future Research ◽

Neurofilament Light ◽

Light Levels ◽

Disability Status ◽

Magnetic Resonance Imaging Mri

In this observational study, 159 patients with multiple sclerosis received personalized dosing of ocrelizumab incentivized by the COVID-19 pandemic. Re-dosing was scheduled when CD19 B-cell count was ⩾10 cells/µL (starting 24 weeks after the previous dose, repeated 4-weekly). Median interval until re-dosing or last B-cell count was 34 [30–38] weeks. No clinical relapses were reported and a minority of patients showed Expanded Disability Status Scale (EDSS) progression. Monthly serum neurofilament light levels remained stable during extended intervals. Two (1.9%) of 107 patients with a follow-up magnetic resonance imaging (MRI) scan showed radiological disease activity. Personalized dosing of ocrelizumab could significantly extend intervals with low short-term disease activity incidence, encouraging future research on long-term safety and efficacy.

Download Full-text

Predicting the profile of increasing disability in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458518790397 ◽

2018 ◽

Vol 25 (9) ◽

pp. 1306-1315 ◽

Cited By ~ 5

Author(s):

Valentina Tomassini ◽

Fulvia Fanelli ◽

Luca Prosperini ◽

Raffaella Cerqua ◽

Paola Cavalla ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Early Recognition ◽

Early Predictors ◽

Disability Status ◽

Preserve Function ◽

Magnetic Resonance Imaging Mri ◽

Individual Disease ◽

Delay Progression

Background: Effective therapeutic strategies to preserve function and delay progression in multiple sclerosis (MS) require early recognition of individual disease trajectories. Objectives: To determine the profiles of disability evolution, identify their early predictors and develop a risk score of increasing disability. Methods: We analysed demographic, clinical and magnetic resonance imaging (MRI) data from patients with relapsing MS, Expanded Disability Status Scale (EDSS) score of 3.0–4.0 and follow-up ≥ 2 years. Attaining EDSS = 6.0 defined increasing disability; relapses and/or MRI defined disease activity. Results: In total, 344 out of 542 (63.5%) patients reached EDSS ≥ 6.0; of these, 220 (64.0%) showed disease activity. In patients with activity, the number of relapses before reaching EDSS 3.0–4.0 predicted increasing disability; age > 45 at baseline predicted increasing disability without activity. Combining age and number of relapses increased the risk of and shortened the time to EDSS = 6.0. Conclusion: Increasing disability is frequently associated with persistent activity. The high number of relapses identifies early those patients worsening in the presence of activity. Age predicts increasing disability in the absence of activity. The presence of both factors increases the risk of developing severe disability. As this study likely describes the transition to progression, our findings contribute to improving patient management and stratification in trials on progressive MS.

Download Full-text