scholarly journals Experiences in treatment of multiple sclerosis with natalizumab from a real-life cohort over 15 years

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael Auer ◽  
Anne Zinganell ◽  
Harald Hegen ◽  
Gabriel Bsteh ◽  
Franziska Di Pauli ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Real Life ◽  
Treatment Discontinuation ◽  
Disease Course ◽  
Highly Active ◽  
Potential Risk Factors ◽  
Risk Of Disease ◽  
Disease Reactivation ◽  
Therapeutic Decision Making

AbstractNatalizumab (NTZ) has been used for treatment of highly active relapsing–remitting multiple sclerosis (MS). When stopping NTZ the risk of severe rebound phenomenon has to be considered. We aimed to investigate the use of NTZ in clinical routine and focused on identification of potential risk factors for disease reactivation after treatment discontinuation. At the Medical University of Innsbruck, Austria, we identified all MS patients who were treated with NTZ and performed a retrospective analysis on therapeutic decision making, disease course before, during and after treatment with NTZ and on risk factors for disease reactivation after NTZ discontinuation. 235 NTZ treated MS patients were included, of whom 105 had discontinued treatment. At NTZ start disease duration was 5.09 (IQR 2.09–10.57) years, average number of total relapses was 4 (IQR 3–6) and median EDSS 2.0 (range 0–6.5), whereby these values significantly decreased over time. Reduction of annualized relapse rate (ARR) on treatment was 93% and EDSS remained stable in 64%. In multivariate regression models only conversion to secondary progressive MS (SPMS) on treatment was significantly associated with lower risk of disease reactivation after NTZ, while ARR before treatment was associated with earlier disease reactivation. We could confirm the high therapeutic efficacy of NTZ which trends to be used earlier in the disease course nowadays. Discontinuation of NTZ seems safe only in patients who convert to SPMS during treatment, while higher ARR before NTZ increases the risk of disease reactivation after treatment discontinuation.

scholarly journals Treatment of Multiple Sclerosis with Natalizumab: Experiences from a Real-Life Cohort Over 15 Years

2021 ◽  
Author(s):  
Michael Auer ◽  
Anne Zinganell ◽  
Harald Hegen ◽  
Gabriel Bsteh ◽  
Franziska Di Pauli ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Real Life ◽  
Disease Course ◽  
Highly Active ◽  
Potential Risk Factors ◽  
Risk Of Disease ◽  
Disease Reactivation ◽  
Therapeutic Decision Making ◽  
Medical University

Abstract BackgroundNatalizumab (NTZ) has been used for treatment of highly active relapsing-remitting multiple sclerosis (MS). When stopping NTZ the risk of severe rebound phenomenon has to be considered. We aimed to investigate the use of NTZ in clinical routine and focused on identification of potential risk factors for disease reactivation after treatment discontinuation.MethodsAt the Medical University of Innsbruck, Austria, we identified all MS patients who were treated with NTZ and performed a retrospective analysis on therapeutic decision making, disease course before, during and after treatment with NTZ and on risk factors for disease reactivation after NTZ discontinuation.Results235 NTZ treated MS patients were included, of whom 105 had discontinued treatment. At NTZ start disease duration was 5.09 (IQR 2.09-10.57) years, average number of total relapses was 4 (IQR 3-6) and median EDSS 2.0 (range 0-6.5), whereby these values significantly decreased over time. Reduction of annualized relapse rate (ARR) on treatment was 93% and EDSS remained stable in 64%. In a multivariate regression model only conversion to secondary progressive MS (SPMS) on treatment was significantly associated with lower risk of disease reactivation after NTZ, while ARR before treatment was associated with earlier disease reactivation. ConclusionsWe could confirm the high therapeutic efficacy of NTZ which trends to be used earlier in the disease course nowadays. Discontinuation of NTZ seems safe only in patients who convert to SPMS during treatment, while higher ARR before NTZ increases the risk of disease reactivation after treatment discontinuation.

scholarly journals Potential risk factors for multiple sclerosis in Rio de Janeiro: a case-control study

2009 ◽  
Vol 67 (2a) ◽  
pp. 229-234 ◽  
Author(s):  
Kátia Regina Penha da Silva ◽  
Regina Maria Papais Alvarenga ◽  
Oscar Fernandez y Fernandez ◽  
Hélcio Alvarenga ◽  
Luiz Claudio Santos Thuler
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Potential Risk ◽  
Rio De Janeiro ◽  
Case Control Study ◽  
Conditional Logistic Regression ◽  
Case Control ◽  
Potential Risk Factors ◽  
Epidemiological Characteristics ◽  
Control Study

PURPOSE: To evaluate potential risk factors for the development of multiple sclerosis in Brazilian patients. METHOD: A case control study was carried out in 81 patients enrolled at the Department of Neurology of the Hospital da Lagoa in Rio de Janeiro, and 81 paired controls. A standardized questionnaire on demographic, social and cultural variables, and medical and family history was used. Statistical analysis was performed using descriptive statistics and conditional logistic regression models with the SPSS for Windows software program. RESULTS: Having standard vaccinations (vaccinations specified by the Brazilian government) (OR=16.2; 95% CI=2.3-115.2), smoking (OR=7.6; 95% CI=2.1-28.2), being single (OR=4.7; 95% CI=1.4-15.6) and eating animal brain (OR=3.4; 95% CI=1.2-9.8) increased the risk of developing MS. CONCLUSIONS: RESULTS of this study may contribute towards better awareness of the epidemiological characteristics of Brazilian patients with multiple sclerosis.

A genetic variant of the anti-apoptotic protein Akt predicts natalizumab-induced lymphocytosis and post-natalizumab multiple sclerosis reactivation

2012 ◽  
Vol 19 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Silvia Rossi ◽  
Caterina Motta ◽  
Valeria Studer ◽  
Fabrizia Monteleone ◽  
Valentina De Chiara ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
At Risk ◽  
Genetic Variant ◽  
Apoptotic Pathway ◽  
Apoptotic Protein ◽  
Natalizumab Treatment ◽  
Patients At Risk ◽  
Risk Of Disease ◽  
Disease Reactivation ◽  
Natalizumab Discontinuation

Background: Multiple sclerosis (MS) patients discontinuing natalizumab treatment are at risk of disease reactivation. No clinical or surrogate parameters exist to identify patients at risk of post-natalizumab MS reactivation. Objective: To determine the role of natalizumab-induced lymphocytosis and of Akt polymorphisms in disease reactivation after natalizumab discontinuation. Methods: Peripheral leukocyte count and composition were monitored in 93 MS patients during natalizumab treatment, and in 56 of these subjects who discontinued the treatment. Genetic variants of the anti-apoptotic protein Akt were determined in all subjects because natalizumab modulates the apoptotic pathway and lymphocyte survival is regulated by the apoptotic cascade. Results: Natalizumab-induced peripheral lymphocytosis protected from post-natalizumab MS reactivation. Subjects who relapsed or had magnetic resonance imaging (MRI) worsening after treatment cessation, in fact, had milder peripheral lymphocyte increases during the treatment, largely caused by less marked T cell increase. Furthermore, subjects carrying a variant of the gene coding for Akt associated with reduced anti-apoptotic efficiency (rs2498804T) had lower lymphocytosis and higher risk of disease reactivation. Conclusion: This study identified one functionally meaningful genetic variant within the Akt signaling pathway that is associated with both lymphocyte count and composition alterations during natalizumab treatment, and with the risk of disease reactivation after natalizumab discontinuation.

scholarly journals Shortening the washout to 4 weeks when switching from natalizumab to fingolimod and risk of disease reactivation in multiple sclerosis

2018 ◽  
Vol 25 ◽  
pp. 14-20 ◽  
Author(s):  
Y. Naegelin ◽  
M. Rasenack ◽  
M. Andelova ◽  
S. Von Felten ◽  
B. Fischer-Barnicol ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Risk Of Disease ◽  
Disease Reactivation

scholarly journals Onset Symptom Clusters in Multiple Sclerosis: Characteristics, Comorbidities, and Risk Factors

2021 ◽  
Vol 12 ◽  
Author(s):  
Vladeta Ajdacic-Gross ◽  
Nina Steinemann ◽  
Gábor Horváth ◽  
Stephanie Rodgers ◽  
Marco Kaufmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Potential Risk ◽  
Latent Class ◽  
Skin Diseases ◽  
Familial Aggregation ◽  
Depression Symptoms ◽  
Latent Classes ◽  
Potential Risk Factors ◽  
Multiple Symptoms

Background: Multiple sclerosis (MS) symptoms are expected to aggregate in specific patterns across different stages of the disease. Here, we studied the clustering of onset symptoms and examined their characteristics, comorbidity patterns and associations with potential risk factors.Methods: Data stem from the Swiss Multiple Sclerosis Registry, a prospective study including 2,063 participants by November 2019. MS onset symptoms were clustered using latent class analysis (LCA). The latent classes were further examined using information on socio-demographic characteristics, MS-related features, potential risk factors, and comorbid diseases.Results: The LCA model with six classes (frequencies ranging from 12 to 24%) was selected for further analyses. The latent classes comprised a multiple symptoms class with high probabilities across several symptoms, contrasting with two classes with solitary onset symptoms: vision problems and paresthesia. Two gait classes emerged between these extremes: the gait-balance class and the gait-paralysis class. The last class was the fatigue-weakness-class, also accompanied by depression symptoms, memory, and gastro-intestinal problems. There was a moderate variation by sex and by MS types. The multiple symptoms class yielded increased comorbidity with other autoimmune disorders. Similar to the fatigue-weakness class, the multiple symptoms class showed associations with angina, skin diseases, migraine, and lifetime prevalence of smoking. Mononucleosis was more frequently reported in the fatigue-weakness and the paresthesia class. Familial aggregation did not differ among the classes.Conclusions: Clustering of MS onset symptoms provides new perspectives on the heterogeneity of MS. The clusters comprise different potential risk factors and comorbidities. They point toward different risk mechanisms.

Pregnancy decision-making in women with multiple sclerosis treated with natalizumab

Neurology ◽  
2018 ◽  
Vol 90 (10) ◽  
pp. e823-e831 ◽  
Author(s):  
Emilio Portaccio ◽  
Pietro Annovazzi ◽  
Angelo Ghezzi ◽  
Mauro Zaffaroni ◽  
Lucia Moiola ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
General Population ◽  
Spontaneous Abortion ◽  
Multivariable Analysis ◽  
Italian Population ◽  
Linear Regression Models ◽  
Class Iii ◽  
Increased Risk ◽  
Risk Of Disease ◽  
Disease Reactivation

ObjectiveTo assess fetal risk after pregnancy exposure to natalizumab in women with multiple sclerosis (MS), with a specific focus on spontaneous abortion (SA) and congenital anomalies (CA).MethodsData of all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents. Rates of SA and CA were also compared with those reported in the Italian population. Multivariable logistic and linear regression models were performed.ResultsA total of 92 pregnancies were tracked in 83 women. In the multivariable analysis, natalizumab exposure was associated with SA (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.9–8.5, p < 0.001). However, the rate of SA (17.4%) was within the estimates for the general population, as well as the rate of major CA (3.7%). Moreover, exposure to natalizumab and interferon-β (IFN-β) was associated with lower length and weight of the babies (p < 0.001).ConclusionOur results showed that natalizumab exposure to up 12 weeks of gestation is associated with an increased risk of SA, although within the limits expected in the general population, whereas the risk of CA needs further investigation. Taking into account the high risk of disease reactivation after natalizumab suspension, pregnancy could be planned continuing natalizumab while strictly monitoring conception.Classification of evidenceThis study provides Class III evidence that in women with MS, natalizumab exposure increases the risk of spontaneous abortion as compared to IFN-β-exposed or untreated patients (OR 3.9, 95% CI 1.9–8.5).

Natural history of secondary-progressive multiple sclerosis

2008 ◽  
Vol 14 (3) ◽  
pp. 314-324 ◽  
Author(s):  
Helen Tremlett ◽  
Yinshan Zhao ◽  
Virginia Devonshire
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Population Based ◽  
Secondary Progressive Multiple Sclerosis ◽  
Older Age ◽  
Secondary Progressive ◽  
Younger Age ◽  
Relapsing Remitting ◽  
Potential Risk Factors

Objective To examine prognosis and risk factors for progression to and from secondary-progressive multiple sclerosis (SPMS).Methods Patients with definite relapsing—remitting MS (RRMS), onset before July 1988, attending a British—Columbian MS clinic before July 1998, and at least one Expanded Disability Status Scale (EDSS) scores were selected from the population-based database. Time to SPMS (from onset and birth) and the subsequent time to EDSS 8 were examined, as were potential risk factors.Results In all, 2484/2837 (87.6%) were relapsing—remitting (RR) at onset, with 1445/2484 (58.2%) reaching SPMS, taking a median 18.9 years (95% CI: 18.2—19.7). Those younger at onset took longer to reach SPMS ( P < 0.0005), but did so at a younger age ( P < 0.0005). Males reached SPMS more rapidly from onset and at a younger age ( P < 0.0005), but were around the same age as females at EDSS 8 ( P = 0.975). Characteristics at SPMS onset associated with a longer time from SPMS to EDSS 8 and an older age at EDSS 8 were: longer disease duration ( P < 0.02), older age ( P < 0.01) and lower EDSS ( P < 0.0005). Onset symptoms had little influence on time to SPMS or subsequent progression.Conclusions The RR phase lasted on average almost two decades, being shorter for males and those older at onset of MS. However, neither were necessarily unfavorable predictors as those older at onset were typically older at SPMS and eventually males and females reached EDSS 8 at around the same age. A longer RR phase was a favorable predictor of disease progression in SPMS. Furthermore, reaching SPMS at an older age or lower EDSS did not necessarily confer a worse outcome. Multiple Sclerosis 2008; 14: 314—324. http://msj.sagepub.com

Pregnancy decision-making in women with multiple sclerosis treated with natalizumab

Neurology ◽  
2018 ◽  
Vol 90 (10) ◽  
pp. e832-e839 ◽  
Author(s):  
Emilio Portaccio ◽  
Lucia Moiola ◽  
Vittorio Martinelli ◽  
Pietro Annovazzi ◽  
Angelo Ghezzi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Repeated Measures ◽  
Multivariable Analysis ◽  
Disease Modifying Drugs ◽  
Maternal Risk ◽  
Logistic Regression Models ◽  
Repeated Measures Analysis ◽  
Risk Of Disease ◽  
Disease Reactivation

ObjectiveTo assess the risk of disease reactivation during pregnancy after natalizumab suspension in women with multiple sclerosis (MS).MethodsData of all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents through a 2-factor repeated measures analysis. Predictors of disease activity were assessed through stepwise multivariable logistic regression models.ResultsA total of 92 pregnancies were tracked in 83 women receiving natalizumab. Among these pregnancies, 74 in 70 women resulted in live births, with a postpartum follow-up of at least 1 year, and were compared with 350 previously published pregnancies. Relapse rate during and after pregnancy was higher in women treated with natalizumab (p < 0.001). In multivariable analysis, longer natalizumab washout period was the only predictor of relapse occurrence during pregnancy (p = 0.001). Relapses in the postpartum year were related to relapses during pregnancy (p = 0.019) and early reintroduction of disease-modifying drugs (DMD; p = 0.021). Disability progression occurred in 16.2% of patients and was reduced by early reintroduction of DMD (p = 0.024).ConclusionsTaken as a whole, our findings indicate that the combination of avoiding natalizumab washout and the early resumption of DMD after delivery could be the best option in the perspective of maternal risk. This approach must take into account possible fetal risks that need to be discussed with the mother and require further investigation.Classification of evidenceThis study provides Class IV evidence that in women with MS, the risk of relapses during pregnancy is higher in those who had been using natalizumab as compared to those who had been using interferon-β or no treatment.

scholarly journals Should I stop or should I go on? Disease modifying therapy after the first clinical episode of multiple sclerosis

2020 ◽  
Author(s):  
Tobias Monschein ◽  
Sabine Salhofer-Polanyi ◽  
Patrick Altmann ◽  
Tobias Zrzavy ◽  
Assunta Dal-Bianco ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Predictive Factor ◽  
Disease Modifying Therapy ◽  
Clinical Episode ◽  
Risk Of Disease ◽  
Disease Reactivation ◽  
Disease Modifying ◽  
In Cis

Abstract Introduction Treatment with disease-modifying therapies (DMT) in patients with clinically isolated syndrome (CIS) represents standard care in multiple sclerosis (MS) patients nowadays. Since a proportion of patients may show no evidence of disease activity (NEDA) after some time of treatment, the question might arise about the risks of stopping DMT. Methods We present a cohort of 49 patients who started DMT immediately after CIS and had no evidence of disease activity (NEDA-3) for at least five years before discontinuation of therapy. Thereafter, patients underwent clinical and MRI follow-up for at least five consecutive years. Results Of 49 patients discontinuing DMT, 53% (n = 26) had NEDA for at least further five years, while 47% (n = 23) showed either a relapse/disease progression (18.4%, n = 9), MRI activity (14.3%, n = 7) or both (14.3%, n = 7). The main predictive factor for sustained NEDA was age at DMT termination. Patients aged > 45 years had a significantly lower risk of disease reactivation (13% vs. 54% in patients aged < 45 years, p < 0.001) after DMT discontinuation. Discussion In CIS patients with immediate DMT after their first clinical episode, older age at the time of DMT discontinuation is the main predictive factor for sustained NEDA status.

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