Clinical outcomes in patients who discontinue natalizumab therapy after 2 years in the Tysabri® Observational Program (TOP)

2020 ◽  
pp. 135245852091792 ◽  
Author(s):  
Helmut Butzkueven ◽  
Maria Trojano ◽  
Ludwig Kappos ◽  
Tim Spelman ◽  
Heinz Wiendl ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Outcomes ◽  
Treatment Duration ◽  
Oral Therapy ◽  
Relapse Risk ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Observational Program

Background: Natalizumab is a highly efficacious therapy for relapsing–remitting multiple sclerosis (RRMS). Patients who discontinue natalizumab may experience return of MS disease activity. Objective: The aim of this study was to analyze predictors of post-natalizumab disease activity return. Methods: The Tysabri® Observational Program (TOP) is an ongoing observational study of natalizumab-treated RRMS patients. Patients discontinuing natalizumab are encouraged to remain in TOP. Results: Analyses included 3221 TOP patients. After ⩾2 years on natalizumab, relapse risk was twice as high for patients who switched to an oral therapy ( n = 660, hazard ratio (HR) = 2.18, p < 0.001) and three times as high for patients who switched to an injectable therapy ( n = 95, HR = 3.02, p < 0.001) as for those who stayed on natalizumab ( n = 2466). Relapse rates after switching remained below pre-natalizumab rates. In patients who switched to an oral therapy, higher relapse risk was predicted by longer washout time, more pre-natalizumab relapses, higher Expanded Disability Status Scale score at natalizumab initiation, and shorter natalizumab treatment duration. Conclusion: Patients who stayed on natalizumab had better clinical outcomes than those who switched to an oral or injectable therapy after ⩾2 years on natalizumab. These results highlight modifiable risk factors for disease activity return (e.g. natalizumab treatment duration and washout duration) to consider when making treatment decisions.

085 Clinical outcomes were better for relapsing-remitting multiple sclerosis (RRMS) patients who remained on natalizumab compared to those who switched to oral or injectable therapies after 2 years in the tysabri® observational program (TOP)

2018 ◽  
Vol 89 (6) ◽  
pp. A34.2-A34
Author(s):  
Helmut Butzkueven ◽  
Ludwig Kappos ◽  
Tim Spelman ◽  
Maria Trojano ◽  
Heinz Wiendl ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Outcomes ◽  
Cox Models ◽  
Relapse Risk ◽  
Lower Baseline ◽  
Relapsing Remitting ◽  
Study Support ◽  
Using Data ◽  
Relapsing Remitting Multiple Sclerosis

IntroductionNatalizumab is a high-efficacy RRMS therapy. Data on post-natalizumab disease activity may be important for physician consideration. We compared outcomes in patients who switched to an oral or injectable therapy or remained on natalizumab and analysed post-natalizumab relapse predictors using data from TOP, an ongoing 10 year observational study of natalizumab-treated RRMS patients.MethodsData from November 2016 were analysed for patients who stayed on natalizumab (≥3 years natalizumab and only natalizumab during follow-up; n=2466; mean time on natalizumab: 5.5 years) or switched to oral (n=660) or injectable (n=95) therapies for ≥1 year after ≥2 years on natalizumab (mean post-natalizumab follow-up 2.5 vs 2.4 years). Annualised relapse rates (ARRs) and Expanded Disability Status Scale (EDSS) worsening risks were evaluated. Disease activity predictors were compared using adjusted Cox models.ResultsRelapse risk was higher for oral switchers (hazard ratio [HR]=2.18; p<0.001) or injectable switchers (HR=3.02; p<0.001) than for patients who stayed on natalizumab >2 years. EDSS worsening risk was similar for oral (HR=1.19; p=0.266) and higher for injectable (HR=2.52; p<0.001) switchers compared with stayed-on-natalizumab patients. ARRs decreased after 2 years by 20.2% for stayed-on-natalizumab patients but increased from on-natalizumab rates by 17.8% in oral switchers (p<0.001) and 108.1% in injectable switchers (p<0.001). In oral switchers, lower relapse risk was predicted by shorter washout time (>12 weeks vs ≤4 weeks; HR=2.03; p<0.001), fewer pre-natalizumab relapses (HR=1.24/relapse in the prior year; p<0.001), lower baseline EDSS (>3.5 vs≤3.5; HR=1.44; p=0.007), and longer natalizumab duration (>3 years vs ≤3 years; HR=0.76; p=0.040).ConclusionStaying on natalizumab >2 years yields better clinical outcomes than switching to oral or injectable therapies. For those discontinuing natalizumab, switching to an oral versus an injectable yields better outcomes. Disease activity risk in oral switchers is predicted by washout time, pre-natalizumab relapses and EDSS, and time on natalizumab.Study supportBiogen.

scholarly journals Switching natalizumab to fingolimod within 6 weeks reduces recurrence of disease activity in MS patients

2017 ◽  
Vol 24 (11) ◽  
pp. 1453-1460 ◽  
Author(s):  
Cyra E Leurs ◽  
Zoé LE van Kempen ◽  
Iris Dekker ◽  
Lisanne J Balk ◽  
Mike P Wattjes ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lymphocyte Count ◽  
Odds Ratio ◽  
Jc Virus ◽  
Observational Cohort Study ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Observational Cohort ◽  
Carry Over ◽  
Relapsing Remitting Multiple Sclerosis

Background: Natalizumab is an effective treatment in relapsing-remitting multiple sclerosis (MS). Mainly because of the risk of progressive multifocal leukoencephalopathy (PML), a substantial proportion of John Cunningham (JC) virus–positive patients switch to fingolimod. Previous reports show a clear benefit when the duration of a washout (WO) period of natalizumab is 0–3 months in comparison to longer WO periods. However, there is no consensus regarding the optimal duration of a WO period under 3 months. Objective: We compared MS disease activity after different WO periods. In addition, we investigated several factors that possibly influence recurrence of disease activity, including serum natalizumab concentration and lymphocyte counts. Methods: From a prospective observational cohort study of natalizumab-treated patients, we selected 52 patients who switched to fingolimod. We divided the patients in three groups (<6 weeks, 6–8 weeks, >8 weeks WO). Serum natalizumab concentration and lymphocyte count were assessed during and after natalizumab treatment. Results: Patients with a WO period of >8 weeks had a significant higher recurrence of disease activity (odds ratio, 6.8; 95% confidence interval, 1.4–32.8) compared to patients with a WO period of <6 weeks. Serum natalizumab concentration and lymphocyte count did not predict recurrence of disease activity. Interpretation: A short WO period decreases the risk of recurrence of disease activity. The possible impact of a short WO period on the risk of carry-over PML in JC virus–positive patients remains uncertain.

Effect of lateral therapy switches to oral moderate-efficacy drugs in multiple sclerosis: a nationwide cohort study

2021 ◽  
pp. jnnp-2020-324869 ◽  
Author(s):  
Mathias Due Buron ◽  
Tomas Kalincik ◽  
Finn Sellebjerg ◽  
Per Soelberg Sørensen ◽  
Melinda Magyari
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Absolute Risk ◽  
Dimethyl Fumarate ◽  
Interferon Β ◽  
First Line ◽  
Disease Modifying Therapies ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

BackgroundSwitching between first-line disease-modifying therapies in patients with clinically stable relapsing–remitting multiple sclerosis (RRMS) due to reasons other than disease activity is frequent, but evidence on the effect of this practice is limited. We investigated the effect of switching patients with stable RRMS on occurrences of disability accumulation, relapses and future treatment discontinuation.MethodsUsing the Danish Multiple Sclerosis Registry, we identified patients with RRMS without disease activity who either (1) stayed on injectable platform therapy (interferon-β or glatiramer acetate) or (2) switched to dimethyl fumarate (DMF) or teriflunomide (TFL) and compared treatment outcomes using propensity-score-based methods and marginal structural models (MSM).ResultsWe included 3206 patients in the study. We found no change in risk of 6-month confirmed Expanded Disability Status Scale score worsening in patients switching to DMF (HR: 1.15, 95% CI 0.88 to 1.50) or TFL (HR: 1.16, 95% CI 0.92 to 1.46). The risk of suffering any relapse tended to decrease when switching to DMF (HR: 0.73, 95% CI 0.51 to 1.04) and tended to increase when switching to TFL (HR: 1.25, 95% CI 0.96 to 1.63). Absolute risk differences were small. MSM analyses showed similar results but did not find an increased relapse risk in TFL switchers.ConclusionSwitching from injectable platform therapies to oral first-line therapies in patients with clinically stable RRMS does not increase the risk of disability accumulation. While the postswitch risk of relapses trended towards marginally higher on TFL, this trend was eliminated by adjustment for time-variant confounders.

Personalized extended interval dosing of natalizumab in MS

Neurology ◽  
2020 ◽  
Vol 95 (6) ◽  
pp. e745-e754
Author(s):  
Zoé L.E. van Kempen ◽  
Erwin L.J. Hoogervorst ◽  
Mike P. Wattjes ◽  
Nynke F. Kalkers ◽  
Jop P. Mostert ◽  
...  
Keyword(s):  
Disease Activity ◽  
Extension Phase ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Mri Scans ◽  
Secondary Endpoints ◽  
Trough Concentrations ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo determine whether natalizumab efficacy is maintained when switching to personalized extended interval dosing based on individual natalizumab trough concentrations in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsThis was a prospective multicenter single-arm trial with 1 year follow-up and a 1-year extension phase. Participants were adult persons with RRMS treated with natalizumab without disease activity in the year prior to enrollment. The natalizumab treatment interval was based on longitudinal natalizumab trough concentrations. Patients received 3 monthly MRI scans, relapse assessments, and disability scoring during follow-up. The primary endpoint was the occurrence of gadolinium-enhancing lesions on MRI. Secondary endpoints were new/enlarging T2 lesions on MRI and relapses and progression on the Expanded Disability Status Scale (EDSS) during follow-up and extension phase.ResultsSixty-one patients were included. Eighty-four percent extended the interval from a 4-week interval to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI] 0%–7.4%) during follow-up. No new/enlarging T2 lesions (95% CI 0%–7.4%) or relapses (95% CI 0%–7.4%) were reported during follow-up and in the extension phase. Median EDSS was comparable at baseline (3.0, interquartile range [IQR] 2.0–5.0) and after follow-up (3.0, IQR 2.0–5.0).ConclusionPersonalized extended interval dosing did not induce recurrence of MS disease activity. Natalizumab efficacy was maintained in stable patients with RRMS receiving personalized extended interval dosing based on individual natalizumab concentrations.Classification of evidenceThis study provides Class IV evidence that personalized extended interval dosing of natalizumab does not result in recurrence of disease activity in stable patients with RRMS.

Course of relapsing–remitting multiple sclerosis before, during and after natalizumab

2010 ◽  
Vol 17 (4) ◽  
pp. 490-494 ◽  
Author(s):  
Michael D Kaufman ◽  
R Lee ◽  
HJ Norton
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Relapse Rate ◽  
Generalized Estimating Equations ◽  
Chart Review ◽  
Relapsing Remitting ◽  
Annualized Relapse Rate ◽  
Natalizumab Treatment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Relapse Rates

The consequences of interruption of natalizumab treatment are incompletely known. The objective was to assess the confirmed annualized relapse rates for patients preceding initiation, during and following suspension of natalizumab therapy. A chart review was conducted and data were analyzed using the Generalized Estimating Equations. During natalizumab therapy the confirmed annualized relapse rate was 0.08, compared to 0.52 ( p = 0.0003) during the prior 12 months and to 0.35 ( p = 0.0032) during the following 3 to 24 months. Similar results were found when confirmed and unconfirmed were analyzed. To conclude, following cessation of natalizumab therapy disease activity rapidly returned to pre-natalizumab levels.

Natalizumab discontinuation after PML risk stratification: outcome from a shared and informed decision

2012 ◽  
Vol 18 (8) ◽  
pp. 1193-1196 ◽  
Author(s):  
Carmen Tur ◽  
Mar Tintoré ◽  
Angela Vidal-Jordana ◽  
Joaquín Castilló ◽  
Ingrid Galán ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Jc Virus ◽  
Risk Groups ◽  
Serological Status ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Group A ◽  
Risk Treatment ◽  
Group B ◽  
Relapsing Remitting Multiple Sclerosis

Multifocal progressive leukoencephalopathy (PML) is associated with JC virus (JCV) seropositivity, past immunosuppression, and natalizumab treatment for two years or more. The aim of our study was to investigate the rate of treatment discontinuation after stratifying for the three risk factors in a group of 104 natalizumab-treated patients with relapsing–remitting multiple sclerosis. We investigated JCV serological status in our population. We then divided patients into groups according to their PML risk. Treatment indication was reassessed. Of the patients, 64 (61.5%) were JCV seropositive. Amongst seropositive patients on natalizumab for 2 years or more, 10 had received immunosuppression (group A), and 38 had not (group B). After an informed and shared decision-making process, 6/10 (60%) from group A compared with 9/38 (23.7%) from group B discontinued treatment ( p=0.027). In groups A and B, discontinuation also depended upon doctors’ views ( p=0.019, group A; p=0.010, group B) and clinical outcomes ( p=0.021, group A). No-one from low–intermediate risk groups discontinued. The decision to discontinue natalizumab treatment is complex, even when clear PML risk rates are described. Clinical outcomes and doctors’ idiosyncrasies play a crucial part in patients’ final choice.

scholarly journals Relationship between Expanded Disability Status Scale scores and the presence of temporomandibular disorders in patients with multiple sclerosis

2018 ◽  
Vol 12 (01) ◽  
pp. 144-148 ◽  
Author(s):  
Lucas Senra Correa Carvalho ◽  
Osvaldo José Moreira Nascimento ◽  
Luciane Lacerda Franco Rocha Rodrigues ◽  
Andre Palma Da Cunha Matta
Keyword(s):  
Multiple Sclerosis ◽  
Temporomandibular Disorders ◽  
Control Group ◽  
Expanded Disability Status Scale ◽  
Exact Test ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Scale Scores ◽  
Axis I ◽  
Relapsing Remitting Multiple Sclerosis

ABSTRACTObjectives: The objectives of this study were to assess the prevalence of temporomandibular disorders (TMDs) in patients with relapsing-remitting multiple sclerosis (MS) and to investigate whether an association exists between the presence of TMD symptoms and the degree of MS-related disability. Materials and Methods: In all, 120 individuals were evaluated: 60 patients with a diagnosis of relapsing-remitting MS and 60 age- and sex-matched controls without neurological impairments. A questionnaire recommended by the European Academy of Craniomandibular Disorders for the assessment of TMD symptoms was administered. For those who answered affirmatively to at least one of the questions, the RDC/TMD Axis I instrument was used for a possible classification of TMD subtypes. The Expanded Disability Status Scale (EDSS) was the measure of the degree of MS-related disability. Statistical Analysis Used: Fisher’s exact test was used to analyze the data. ANOVA was used to detect significant differences between means and to assess whether the factors influenced any of the dependent variables by comparing means from the different groups. Results: The prevalence of TMD symptoms in patients with MS was 61.7% versus 18.3% in the control group (CG). A diagnosis of TMD was established for 36.7% in the MS group and 3.3% in the CG (P = 0.0001). There were statistically significant differences between degrees of MS-related disability and the prevalence of TMD (P = 0.0288). Conclusions: The prevalence of both TMD and TMD symptoms was significantly greater in the MS group. EDSS scores and TMD prevalence rates were inversely related.

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