Safety of Exposure to Natalizumab During Pregnancy

Study Overview
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Brief Summary
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Multiple sclerosis (MS) preferentially affects young adults with a female predominance. MS is not associated with an increased risk of complications or abnormal pregnancy outcomes. Nevertheless, disease-modifying therapies can have a teratogenic effect. Discussions about discontinuation should be made with a view to or upon discovery of pregnancy, taking into account the risk of untreated relapses and the risk of toxicity to the fetus. Natalizumab (NTZ) is a humanized anti-alpha4-integrin monoclonal antibody used as a treatment for highly active relapsing-remitting MS (RRMS). When it is stopped, there is frequent reactivation of the disease with possible relapses and a rebound effect could occur. At present, depending on the center, attitudes of neurologist may vary and 3 main scenarios can be observed: Pregnancy and postpartum under NTZ (group1), Pregnancy partially under NTZ (with or without immunomodulator (IM) supplementation, group 2), or NTZ stopped before pregnancy (with or without IM supplementation, group3). The first part of the BABYZUMAB study, a retrospective study of Natalizumab exposure during pregnancy, analysed the comparison the clinical activity of the disease (annualized relapse rate) according to these 3 scenarios of NTZ treatment The investigators analyzed the annual relapse rate (ARR) during a two-year period (9 months before and 15 months after the beginning of the pregnancy) in 117 patients identified in the OFSEP database. The investigators showed that the risk of relapses was four times higher in Group 2 versus Group 1 (p=0,014) and six times higher in Group 3 versus Group 1 (p=0,001). In the literature, there are few studies of newborns from NTZ-exposed pregnancies. No specific pattern of birth defects has been found, but mild to moderate transient thrombocytopenia and anemia have been reported in infants born to NTZ-exposed mothers in the third trimester of pregnancy.

Official Title
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Safety of Exposure to Natalizumab During Pregnancy

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Behavioral: Questionnaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 years at the index date (date of pregnancy onset) of data collection, RRMS according to McDonald's 2017 criteria (Thompson et al., 2018) Affiliated person or beneficiary of a social security scheme. followed up at one of the participating centers (OFSEP centers) NTZ exposure during pregnancy according to 3 pre-defined sub-groups: continuation of NTZ throughout pregnancy and postpartum (Group 1), exposure during the first trimester (Group 2) exposure during the first and the second trimester (Group 3). Participants capable of expressing non objection French-speaking, without comprehension disorders Exclusion Criteria: Patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>continuation of NTZ throughout pregnancy and postpartum | Behavioral: Questionnaire<br>* Questionnaire<br>|
| Group 2<br>exposure during the first trimester | Behavioral: Questionnaire<br>* Questionnaire<br>|
| Group 3<br>exposure during the first and the second trimester | Behavioral: Questionnaire<br>* Questionnaire<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who presented serious adverse events (SAE) during their pregnancy |  | At baseline (Day 0) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who presented pregnancy complications |  | At baseline (day 0) | 
| Proportion of patients who presented delivery complications |  | At baseline (day 0) | 
| Proportion of patients who presented postpartum AEs of interest |  | At baseline (day 0) | 
| Proportion of viable children at birth |  | At baseline (day 0) | 
| Average weight at birth |  | At baseline (day 0) | 
| apgar score at birth |  | At baseline (day 0) | 
| Number of child AEs of interest (haematological, infectious, malformations) at birth |  | At baseline (day 0) | 
| Number of child AEs of interest (haematological, infectious, malformations) two years after birth |  | At baseline (day 0) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Natalizumab, Safety, pregnancy