The effects of long-term exposure to disease-modifying drugs during pregnancy in multiple sclerosis

Fragoso, Yára Dadalti; Boggild, Mike; Macías-Islas, Miguel Ángel; Carrá, Adriana; Schaerer, K; Aguayo, Adriana; Almeida, Sandra Maria Garcia de; Alvarenga, Marcos Papais; Alves-Leon, Soniza Vieira; Arruda, Walter Oleschko; Brooks, Joseph Bruno Bidin; Comini-Frota, Elizabeth Regina; Ferreira, Maria Lúcia Brito; Finkelsztejn, Alessandro; Finkelsztejn, Juliana; Freitas, Lucas Dias de; Gallina, Andre S.; Gama, Paulo Diniz da; Georgetto, Sergio; Giacomo, Maria Cristina B.; Gomes, Sidney; Gonçalves, Marcus Vinícius Magno; Grzesiuk, Anderson Kuntz; Kaimen-Maciel, Damacio Ramón; Lopes, Josiane; Lourenço, Giselle; Malfetano, Fabíola Rachid; Morales, Norberto; Morales, Rogério de Rizo; Oliveira, Celso Luis Silva; Onaha, P.; Patroclo, Cristiane Borges; Ribeiro, Sonia Beatriz Felix; Ribeiro, T.A.G.J.; Salminen, Heidi; Santoro, Paula Freire; SEEFELD, Marcos; Soares, Paula Vallegas; Tarulla, Adriana; Vasconcelos, Cláudia Cristina Ferreira

doi:10.1016/j.clineuro.2012.04.024

Cited by 74 publications

(86 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%

“…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%

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

et al. 2018

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“…In particular, two large registries reported spontaneous abortion frequencies of 11.5 and 8 % of cases, respectively [83,102]. Moreover, the occurrence of malformations or developmental abnormalities has been described in some studies, but the overall frequency does not seem to be different from that of the normal population [83,90,[102][103][104]. Finally, a lower body weight has been observed in some studies [83,[103][104][105] but not confirmed by others [106,107].…”

Section: Pregnancy and Foetal Developmentmentioning

confidence: 82%

Fertility, Pregnancy and Childbirth in Patients with Multiple Sclerosis: Impact of Disease-Modifying Drugs

Amato

Portaccio

2015

CNS Drugs

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In recent decades, pregnancy-related issues in multiple sclerosis (MS) have received growing interest. MS is more frequent in women than in men and typically starts during child-bearing age. An increasing number of disease-modifying drugs (DMDs) for the treatment of MS are becoming available. Gathering information on their influences on pregnancy-related issues is of crucial importance for the counselling of MS patients. As for the immunomodulatory drugs (interferons and glatiramer acetate), accumulating evidence points to the relative safety of pregnancy exposure in terms of maternal and foetal outcomes. In case of higher clinical disease activity before pregnancy, these drugs could be continued until conception. As for the 'newer' drugs (fingolimod, natalizumab, teriflunomide, dimethyl fumarate and alemtuzumab), the information is more limited. Whereas fingolimod and teriflunomide are likely associated with an increased risk of foetal malformations, the effects of natalizumab, dimethyl fumarate and alemtuzumab still need to be ascertained. This article provides a review of the available information on the use of DMDs during pregnancy, with a specific focus on fertility, foetal development, delivery and breast-feeding.

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“…At the sixth stage of development, the eggs were washed Group 2(n=20)(10μl GA) 4 (20) 16 (80) with 70% alcohol and labeled properly on the outer shell. A hole was made on the blunt pole of the eggs with a sharp and thick needle.…”

Section: Methods Of Injectionmentioning

confidence: 99%

Targeting apoptosis through foxp1, and n-cadherin with glatiramer acetate in chick embryos during neural tube development

Taşkapılıoğlu¹,

Billur²,

Kizil³

et al. 2015

Turkish Neurosurgery

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ABSTRACTtheir childbearing ages of 20 to 45 (20, 34, 35). The issue of pregnancy planning in these patients makes treatment tricky.Glatiramer acetate (GA), one of the first-line therapies currently approved for relapsing-remitting multiple sclerosis (RRMS) (34), was originally designed as a synthetic analogue of myelin basic protein (1). Data about exposure to GA during early pregnancy period in humans is limited but animal studies have revealed no fetal risk to date so GA is classified by █ INTRODUCTIONNeural tube (NT) defects are uncommon malformations occurring 6 in 10000 pregnancies (60). Congenital malformation incidence is 3-5% in newborns and NT defects cause 7% of newborn deaths related to congenital malformations (13).Multiple Sclerosis (MS), a chronic demyelinating and degenerative disease of the central nervous system (CNS), is the most common chronic neurologic disability in young adults in AIM: To demonstrate the effect of glatiramer acetate (GA) in chick embryos on neural tube (NT) development, and to explore its effects of FOXP1, apoptosis, and N-cadherin. MATERIAL and METHODS:One hundred fertile, specific pathogen free eggs were divided into 5 groups for this study. The eggshell was windowed specifically at 24 hours of incubation. The embryos in Group 1 (n=20) were treated with 10 μl physiological saline; in Group 2 the embryos (n=20) were given 10 μl GA (equal to daily human therapeutic dose); 20 μl GA (equal to twice daily human therapeutic dose) was injected to embryos in Group 3 (n=20); in Group 4 and 5, 30 μl and 40 μl GA were administered to the embryos (n=20) (equal to x3 and x4 daily human therapeutic dose, respectively). Each egg was re-incubated for 24 hours more. Then, histological and immunohistochemical evaluation of the subjects were done. RESULTS:The embryos with NT defect showed FOXP1 expression without N-cadherin or staining with N-cadherin in another location in our study. We interpreted this result as GA leading to an NT closure defect by increasing FOXP expression. Moreover, we also showed the reverse relation between FOXP1 and N-cadherin at the immunohistochemical level for the first time. CONCLUSION:GA affects the spinal cord development through FOXP in the chick embryo model at high doses.

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The effects of long-term exposure to disease-modifying drugs during pregnancy in multiple sclerosis

Cited by 74 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

Fertility, Pregnancy and Childbirth in Patients with Multiple Sclerosis: Impact of Disease-Modifying Drugs

Targeting apoptosis through foxp1, and n-cadherin with glatiramer acetate in chick embryos during neural tube development

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