Clinical trial NCT05209815: Safety of Exposure to Natalizumab During Pregnancy
Official title: Safety of Exposure to Natalizumab During Pregnancy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Keywords: Natalizumab
Safety
pregnancy
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Biogen
First posted: 2022-01-27
Enrollment: 68
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient aged over 18 years old, affected by RRMS according to McDonald's 2017 criteria identified in the BABYZUMAB-1 study

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Proportion of patients who presented serious adverse events (SAE) during their pregnancy
timeFrame: At baseline (Day 0)
Secondary outcomes:
measure: Proportion of patients who presented pregnancy complications
timeFrame: At baseline (day 0)
measure: Proportion of patients who presented delivery complications
timeFrame: At baseline (day 0)
measure: Proportion of patients who presented postpartum AEs of interest
timeFrame: At baseline (day 0)
measure: Proportion of viable children at birth
timeFrame: At baseline (day 0)
measure: Average weight at birth
timeFrame: At baseline (day 0)
measure: apgar score at birth
timeFrame: At baseline (day 0)
measure: Number of child AEs of interest (haematological, infectious, malformations) at birth
timeFrame: At baseline (day 0)
measure: Number of child AEs of interest (haematological, infectious, malformations) two years after birth
timeFrame: At baseline (day 0)
Other outcomes:
Locations:
city: Besançon
country: France
facility: CHRU de Besançon - service de neurologie
city: Bordeaux
country: France
facility: CHU de Bordeaux - service de neurologie
city: Bron
country: France
facility: HCL - service de neurologie
city: Corbeil-Essonnes
country: France
facility: CH Sud Francilien - service de neurologie
city: Créteil
country: France
facility: AP-HP - Hôpital de Créteil - service de neurologie
city: Dijon
country: France
facility: CHU de Dijon-Bourgogne
city: La Tronche
country: France
facility: CHU de Grenoble-Alpes
city: Lille
country: France
facility: CHRU de Lille - service de neurologie
city: Limoges
country: France
facility: CHU de Limoges - service de neurologie
city: Marseille
country: France
facility: AP-HM - service de neurologie
city: Montpellier
country: France
facility: CHU de Montpellier - service de neurologie
city: Nancy
country: France
facility: CHRU de Nancy - service de neurologie
city: Nantes
country: France
facility: CHU de Nantes - service de neurologie
city: Nice
country: France
facility: CHU de Nice - service de neurologie
city: Nîmes
country: France
facility: CHU de Nîmes - service de neurologie
city: Paris
country: France
facility: AP-HP - Hôpital La Pitié Salpétrière - service de neurologie
city: Paris
country: France
facility: AP-HP - Hôpital Saint-Antoine - service de neurologie
city: Paris
country: France
facility: Fondation Rothschild - service de neurologie
city: Poitiers
country: France
facility: CHU de Poitiers - service de neurologie
city: Rennes
country: France
facility: CHU de Rennes - service de neurologie
city: Rouen
country: France
facility: CHU de Rouen - service de neurologie
city: Saint-Denis
country: France
facility: CH de Saint-Denis - service de neurologie
city: Salouël
country: France
facility: CHU d'Amiens - service de neurologie
city: Strasbourg
country: France
facility: CHRU de Strasbourg - service de neurologie
city: Toulouse
country: France
facility: CHU de Toulouse - service de neurologie
city: Tours
country: France
facility: CHU de Tours - service de neurologie
city: Fort-de-France
country: Martinique
facility: CHU de Fort de France - service de neurologie
Study officials:
affiliation: University Hospital, Bordeaux
name: Aurélie RUET, Prof
role: PRINCIPAL_INVESTIGATOR
References: