Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study

Ebrahimi, Neda; Herbstritt, Sandra; Gold, R.; Amezcua, Lilyana; Koren, Gideon; Hellwig, Kerstin

doi:10.1177/1352458514546790

Cited by 111 publications

(81 citation statements)

References 17 publications

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“…The risk of selective outcome reporting could not be assessed because no study protocols were available. The classification of participants as exposed or unexposed was not a problem in several studies 149,150,[153][154][155]158,159,[161][162][163][164][165] as exposed status was clearly defined and classification was unlikely to have been affected by knowledge of the outcomes as they were measured prospectively. However, in some studies, information used to define DMT exposure was recorded retrospectively after delivery; therefore, infant outcomes may have biased recall of prior exposure.…”

Section: Exposure To Other Disease-modifying Treatmentsmentioning

confidence: 99%

“…One study with a serious risk of bias compared exposure to natalizumab with interferon or glatiramer acetate and suggested little difference between the groups in the proportion of infants born with low birth weight but a higher risk of spontaneous abortion in the group exposed to interferon or glatiramer acetate (21.1% vs 17.4%) and a higher proportion of infants with congenital malformations in the group exposed to natalizumab (3.9% vs 1.4%). 159 Compared to women who were not exposed to DMDs, evidence with a serious risk of bias indicated a higher proportion of women experiencing a spontaneous abortion in those exposed to natalizumab but a higher proportion of infants born with a congenital malformation in the unexposed group. 161 Further details of the study results are presented in Supplementary Appendix 9 - Table 4.…”

Section: Recommendationsmentioning

confidence: 99%

“…Several studies investigated the impact of exposure to interferon beta and/or glatiramer acetate, [144][145][146][147][148][149][150][151][152][153][154][155][156][157][158] while fewer and more recent ones explored the effect of natalizumab, [159][160][161] dimethyl fumarate, 162 teriflunomide 163 and fingolimod. 164 In most studies, women were classified as being exposed to a DMT, provided the last dose/injection of drug was administered after the last menstrual period before conception.…”

Section: Recommendationsmentioning

confidence: 99%

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ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

et al. 2018

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Background and scopeMultiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS) that is characterized by inflammation, demyelination and degenerative changes. MS usually begins around the age between 20 and 40 years and affects two to three times as many women as men; it also constitutes the most frequent cause of non-traumatic disability in the young adult population. 1 The incidence of MS varies across regions, with rates as high as 8 to 10 new cases per 100,000 in high latitudinal regions. 2,3 Current estimates suggest that over 700,000 people are affected in Europe, with over 2.5 million cases worldwide, 4 which represent a significant burden in terms of impact on quality of life, societal costs and personal expenses. 5,6 Most patients (85%-90%) have a relapsing course from onset that is characterized by relapses and remissions of neurological symptoms Methods: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations. Clinical questions were formulated in Patients-Intervention-Comparator-Outcome (PICO) format and outcomes were prioritized. The quality of evidence was rated into four categories according to the risk of bias. The recommendations with assigned strength (strong and weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. Results: A total of 10 questions were agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency (EMA) at the time of publication. A total of 21 recommendations were agreed by the guideline working group after three rounds of consensus. Conclusion:The present guideline will enable homogeneity of treatment decisions across Europe. associated with areas of CNS inflammation, and over the course of two decades, more than half of untreated patients transition to a phase of gradual worsening independent of acute attacks. 7,8 Progressive forms of MS can be present as the initial disease course (primary-progressive MS) in approximately 10%-15% of patients. 9,10 There is no curative treatment available for MS, and the current therapeutic strategy is aimed at reducing the risk of relapses and potentially disability progression. The treatment era for MS began in 1993, when the first interferon became available, and recent years have seen a large expansion in the therapeutic options for MS, with 11 disease-modifying therapies (DMTs) approved by the European Medicine Agency (EMA) in both injectable and oral formulations by the beginning of 2017. 11 The growing armamentarium of therapies brings new opportunities for individualized therapy where patients and providers must balance considerations around efficacy,...

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Section: Exposure To Other Disease-modifying Treatmentsmentioning

confidence: 99%

Section: Recommendationsmentioning

confidence: 99%

Section: Recommendationsmentioning

confidence: 99%

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ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

et al. 2018

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“…However, no human implantation or embryonic defects have been reported, and no cardiac issues have been found [Cree, 2013]. In a recent prospective, controlled, observational study, 101 MS women exposed to natalizumab in the first trimester were compared with 78 pregnant MS women without DMT exposure, and 97 healthy control women [Ebrahimi et al 2015]. There was no difference in major malformations, low birth weight, or premature births.…”

Section: Disease-modifying Therapiesmentioning

confidence: 99%

Management of women with multiple sclerosis through pregnancy and after childbirth

Coyle

2016

Ther Adv Neurol Disord

121

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Multiple sclerosis (MS) is a major acquired neurologic disease of young adults. The prototypic patient is a young woman of reproductive age. Gender preference is becoming more pronounced, since MS is increasing specifically among women. Any healthcare provider who deals with MS must be prepared to discuss pregnancy issues, and provide appropriate counseling. This is now complicated by the availability of multiple treatment options. There is growing literature on which to base recommendations, particularly regarding washout periods. After a brief background introduction, this review will discuss state-of-the-art family planning counseling in the treatment era, divided into prepregnancy, pregnancy, and postpartum MS issues.

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“…The rate of major defects rate was the same as in the general population and there was no increased abortion rate. In this issue, Ebrahimi et al 4 report on 101 women who were exposed to NZB around conception time and who experienced 102 deliveries. They had received an average of 18 NZB infusions before becoming pregnant.…”

mentioning

confidence: 99%

How safe is natalizumab during pregnancy?

Duquette

Prat

2014

Mult Scler

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Women with multiple sclerosis (MS) want to enjoy life to the full, including giving birth to and raising children. MS, in itself, has little impact on the course of pregnancy. It is well established that disease activity is considerably reduced during the last two trimesters of pregnancy. 1 Breast-feeding has a neutral effect on MS course. We have reported that pregnancy may hasten transition to secondary progression. 2 Family planning for a woman with MS must consider the following: a 3-5% risk of MS transmission to the child, treatment cessation, a post-partum relapse rate of around 30%, resumption of disease-modifying therapies (DMT), and the possibility of a lessened capacity to take care of the child. The only demonstrated effects of standard DMTs on pregnancy outcomes are a slightly decreased child birth weight and length, and an increased rate of spontaneous abortions with interferons. 3 Uncertainty remains over some possible long-term effects of treatments on the child. Women are generally unwilling to take any DMT during pregnancy, so that treatment is almost always deferred. DMT interruption carries the risk of disease reactivation, so that it is now advised to continue DMTs until a pregnancy test is positive. There is still, though, a high percentage of unplanned pregnancies. Natalizumab (NZB) is highly effective in reducing clinical and magnetic resonance imaging (MRI) manifestations of MS. Its use as a 4-weekly IV infusion is convenient, and is well tolerated in the short term. Alpha4-integrin, which is the target of NZB, plays an active role in fertilization, implantation, placental and cardiac development. When antagonized with NZB in pregnant animals, severe birth defects have been reported. Risks associated with NZB exposures during pregnancy and potential adverse effects on the developing fetus have therefore been expected.There are some reports of NZB exposure during pregnancy. In the manufacturer's (Biogen-Idec) registry on 364 pregnancies on NZB, mostly after very short and early exposure, 30 children (8%) had birth defects, mostly mild. The rate of major defects rate was the same as in the general population and there was no increased abortion rate. In this issue, Ebrahimi et al. 4 report on 101 women who were exposed to NZB around conception time and who experienced 102 deliveries. They had received an average of 18 NZB infusions before becoming pregnant. Only one of these women was exposed during the third trimester of pregnancy. The others 100 were exposed shortly before conception, or during the first few weeks of pregnancy. Ebrahimi et al.'s data uncover a higher miscarriage rate and lower birth weights in NZBtreated women, when compared with healthy controls. Amongst the non-live births, three fetuses had genetic anomalies. Rates of major malformations, low birth weight, and premature birth were not different from those found in the general population. Twentyone women experienced a relapse during pregnancy that required at least one course of steroid treatment. There is no mention of ...

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Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study

Abstract: Exposure to natalizumab in early pregnancy does not appear to increase the risk of adverse pregnancy outcomes in comparison to a DM group not exposed to natalizumab.

Cited by 111 publications

References 17 publications

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

Management of women with multiple sclerosis through pregnancy and after childbirth

How safe is natalizumab during pregnancy?

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