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).

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 Pregnancy and the Use of Disease-Modifying Therapies in Patients with Multiple Sclerosis: Benefits versus Risks

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Raed Alroughani ◽  
Ayse Altintas ◽  
Mohammed Al Jumah ◽  
Mohammadali Sahraian ◽  
Issa Alsharoqi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Current Evidence ◽  
Disease Modifying Therapies ◽  
Increased Risk ◽  
Pregnancy And Lactation ◽  
Risk Of Disease ◽  
Disease Reactivation ◽  
Disease Modifying ◽  
Adverse Pregnancy ◽  
In Pregnancy

The burden of multiple sclerosis (MS) in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs), which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-βappears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation.

scholarly journals Left ventricular mechanical dispersion in a general population: Data from the Akershus Cardiac Examination 1950 study

2019 ◽  
Author(s):  
Erika N Aagaard ◽  
Brede Kvisvik ◽  
Mohammad O Pervez ◽  
Magnus N Lyngbakken ◽  
Trygve Berge ◽  
...  
Keyword(s):  
General Population ◽  
Global Longitudinal Strain ◽  
Population Data ◽  
Left Ventricular ◽  
Linear Regression Models ◽  
Cross Sectional ◽  
Clinical Model ◽  
Mechanical Dispersion ◽  
Obesity And Diabetes ◽  
Increased Risk

Abstract Aims Increased left ventricular mechanical dispersion by 2D speckle tracking echocardiography predicts ventricular arrhythmias in ischaemic heart disease and heart failure. However, little is known about mechanical dispersion in the general population. We aimed to study mechanical dispersion in the general population and in diseases associated with increased risk of cardiovascular disease. Methods and results The present cross-sectional study consists of 2529 subjects born in 1950 included in the Akershus Cardiac Examination (ACE) 1950 study. Global longitudinal strain (GLS) was assessed from 17 strain segments, and mechanical dispersion calculated as the standard deviation of contraction duration of all segments. The cohort was divided according to the median value of mechanical dispersion, and multivariable linear regression models were performed with mechanical dispersion as the dependent variable. The prevalence of coronary artery disease (CAD), hypertension, obesity, and diabetes (P < 0.01 for all) was significantly higher in subjects with supra-median mechanical dispersion. In a multivariable clinical model, CAD (B = 7.05), hypertension (B = 4.15; both P < 0.001), diabetes (B = 3.39), and obesity (B = 1.89; both P < 0.05) were independently associated with increasing mechanical dispersion. When echocardiographic indices were added to the multivariable model, CAD (B = 4.38; P < 0.01) and hypertension (B = 2.86; P < 0.001) remained significant in addition to peak early diastolic tissue velocity e’ (B = −2.00), GLS (B = 1.68), and ejection fraction (B = 0.22; P < 0.001 for all). Conclusion In a general middle-aged population, prevalent CAD and hypertension were associated with increasing mechanical dispersion, possibly indicating elevated risk of fatal arrhythmias and sudden cardiac death. Albeit weaker, systolic and diastolic dysfunction, were also associated with increasing mechanical dispersion.

scholarly journals Post-natalizumab disease reactivation in multiple sclerosis: systematic review and meta-analysis

2019 ◽  
Vol 12 ◽  
pp. 175628641983780 ◽  
Author(s):  
Luca Prosperini ◽  
Revere P. Kinkel ◽  
Augusto A. Miravalle ◽  
Pietro Iaffaldano ◽  
Simone Fantaccini
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Disease Activity ◽  
Meta Analysis ◽  
Random Effect ◽  
Patient Characteristics ◽  
Increased Risk ◽  
Disease Reactivation ◽  
Definition Of ◽  
High Level

Background: Natalizumab (NTZ) is sometimes discontinued in patients with multiple sclerosis, mainly due to concerns about the risk of progressive multifocal leukoencephalopathy. However, NTZ interruption may result in recrudescence of disease activity. Objective: The objective of this study was to summarize the available evidence about NTZ discontinuation and to identify which patients will experience post-NTZ disease reactivation through meta-analysis of existing literature data. Methods: PubMed was searched for articles reporting the effects of NTZ withdrawal in adult patients (⩾18 years) with relapsing–remitting multiple sclerosis (RRMS). Definition of disease activity following NTZ discontinuation, proportion of patients who experienced post-NTZ disease reactivation, and timing to NTZ discontinuation to disease reactivation were systematically reviewed. A generic inverse variance with random effect was used to calculate the weighted effect of patients’ clinical characteristics on the risk of post-NTZ disease reactivation, defined as the occurrence of at least one relapse. Results: The original search identified 205 publications. Thirty-five articles were included in the systematic review. We found a high level of heterogeneity across studies in terms of sample size (10 to 1866 patients), baseline patient characteristics, follow up (1–24 months), outcome measures (clinical and/or radiological), and definition of post-NTZ disease reactivation or rebound. Clinical relapses were observed in 9–80% of patients and peaked at 4–7 months, whereas radiological disease activity was observed in 7–87% of patients starting at 6 weeks following NTZ discontinuation. The meta-analysis of six articles, yielding a total of 1183 patients, revealed that younger age, higher number of relapses and gadolinium-enhanced lesions before treatment start, and fewer NTZ infusions were associated with increased risk for post-NTZ disease reactivation ( p ⩽ 0.05). Conclusions: Results from the present review and meta-analysis can help to profile patients who are at greater risk of post-NTZ disease reactivation. However, potential reporting bias and variability in selected studies should be taken into account when interpreting our data.

Conjugal multiple sclerosis in Isfahan, Iran: a population-based study

2007 ◽  
Vol 13 (5) ◽  
pp. 673-675 ◽  
Author(s):  
A.H. Maghzi ◽  
M. Etemadifar ◽  
V. Shaygannejad ◽  
M. Saadatnia ◽  
M. Salehi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
General Population ◽  
Environmental Factors ◽  
Adult Life ◽  
Marital Relationship ◽  
Population Based ◽  
Rare Form ◽  
Population Based Study ◽  
Increased Risk ◽  
Estimated Risk

Conjugal multiple sclerosis (MS) is a rare form of MS in which both spouses are affected, and at least one is affected after marriage. Among 1606 definite MS patients, 1076 were in marital relationship, among whom we identified six conjugal pairs, giving the conjugal rate of 0.5%. This rate is 12.5 times higher than the estimated risk of MS for the general population (0.04%). The observed conjugal rate suggests an increased risk of developing MS for MS patients' spouses, this could be due to transmission or, more likely, to the same environmental factors shared in adult life. Multiple Sclerosis 2007; 13: 673-675. http://msj.sagepub.com

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 Patients with Inflammatory Bowel Disease Are Not at Increased Risk of COVID-19: A Large Multinational Cohort Study

2020 ◽  
Vol 9 (11) ◽  
pp. 3533
Author(s):  
Mariangela Allocca ◽  
María Chaparro ◽  
Haidee Aleman Gonzalez ◽  
Marta Maia Bosca-Watts ◽  
Carolina Palmela ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Monoclonal Antibodies ◽  
General Population ◽  
Bowel Disease ◽  
Detrimental Effect ◽  
Multivariable Analysis ◽  
Increased Risk ◽  
Containment Measures ◽  
Inflammatory Bowel ◽  
The Impact

The impact of COVID-19 on inflammatory bowel disease (IBD) patients under pharmacological immunosuppression is still not clearly understood. We investigated the incidence of COVID-19 and the impact of immunosuppression and containment measures on the risk of SARS-CoV-2 infection in a large IBD cohort, from a multicenter cohort from 21st of February to 30th of June, 2020. Ninety-seven patients with IBD (43 UC, 53 CD, one unclassified IBD) and concomitant COVID-19 over a total of 23,879 patients with IBD were enrolled in the study. The cumulative incidence of SARS-CoV-2 infection in patients with IBD vs. the general population was 0.406% and 0.402% cases, respectively. Twenty-three patients (24%) were hospitalized, 21 (22%) had pneumonia, four (4%) were admitted to the Intensive Care Unit, and one patient died. Lethality in our cohort was 1% compared to 9% in the general population. At multivariable analysis, age > 65 years was associated with increased risk of pneumonia and hospitalization (OR 11.6, 95% CI 2.18–62.60; OR 5.1, 95% CI 1.10–23.86, respectively), treatment with corticosteroids increased the risk of hospitalization (OR 7.6, 95% CI 1.48–40.05), whereas monoclonal antibodies were associated with reduced risk of pneumonia and hospitalization (OR 0.1, 95% CI 0.04–0.52; OR 0.3, 95% CI 0.10–0.90, respectively). The risk of COVID-19 in patients with IBD is similar to the general population. National lockdown was effective in preventing infection in our cohort. Advanced age and treatment with corticosteroids impacted negatively on the outcome of COVID-19, whereas monoclonal antibodies did not seem to have a detrimental effect.

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.

An excessive risk of suicide may no longer be a reality for multiple sclerosis patients

2017 ◽  
Vol 23 (6) ◽  
pp. 864-871 ◽  
Author(s):  
Shoshannah Kalson-Ray ◽  
Gilles Edan ◽  
Emmanuelle Leray ◽  
Keyword(s):  
Multiple Sclerosis ◽  
General Population ◽  
Population Based ◽  
Sensitivity Analyses ◽  
Clinical Onset ◽  
Increased Risk ◽  
Multiple Sclerosis Patients ◽  
Mean Time ◽  
Long Term Mortality

Background: Few recent studies have shown that there is no longer an increased risk of suicide in patients affected with multiple sclerosis (MS). Objectives: To describe suicide cases within a large French MS cohort and assess whether MS patients are at a higher risk of suicide compared with the general population. Methods: Data derives from a study on long-term mortality of 27,603 prevalent cases from 15 MS specialist centres. Of 1,569 deceased MS patients (5.7%) on 1 January 2010, 47 were suicides. Results: The mean time between MS clinical onset and death was 13.5 years (standard deviation (SD): 9.3 years; none within the first 3 years) and was significantly shorter than for MS patients who had died from other causes (mean = 21.4 (SD = 11.6), p < 0.0001). Age at death was also lower (46.3 vs 56.7). The standardized mortality rates were around 1 in several sensitivity analyses, reflecting no excess mortality in MS compared with general population. Conclusion: Our findings indicate that an excess suicide risk may no longer be true for MS patients and highlight the changing profile of cases, occurring later in the disease course. Further studies in population-based registries are needed to confirm and explain these potential changes (e.g. treatments’ impact?).

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