Safety of Exposure to Natalizumab During Pregnancy

NCT05209815 | Completed

• 1 other identifier: CHUBX 2020/65
• Study Type: observational
• Target: 68
• Locations: 2 countries
• Sites: 27

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.

Conditions

Multiple Sclerosis

Keywords

Natalizumab; Safety; pregnancy

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who presented serious adverse events (SAE) during their pregnancy

  At baseline (Day 0)

Secondary Outcomes (8)

• 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)

Study Arms (3)

Group 1

continuation of NTZ throughout pregnancy and postpartum

Behavioral: Questionnaire

Group 2

exposure during the first trimester

Behavioral: Questionnaire

Group 3

exposure during the first and the second trimester

Behavioral: Questionnaire

Interventions

Questionnaire BEHAVIORAL

Questionnaire

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Biogen: collaborator

Study Sites (27)

CHRU de Besançon - service de neurologie

Besançon, France

Location

CHU de Bordeaux - service de neurologie

Bordeaux, France

Location

HCL - service de neurologie

Bron, France

Location

CH Sud Francilien - service de neurologie

Corbeil-Essonnes, France

Location

AP-HP - Hôpital de Créteil - service de neurologie

Créteil, France

Location

CHU de Dijon-Bourgogne

Dijon, France

Location

CHU de Grenoble-Alpes

La Tronche, France

Location

CHRU de Lille - service de neurologie

Lille, France

Location

CHU de Limoges - service de neurologie

Limoges, France

Location

AP-HM - service de neurologie

Marseille, France

Location

CHU de Montpellier - service de neurologie

Montpellier, France

Location

CHRU de Nancy - service de neurologie

Nancy, France

Location

CHU de Nantes - service de neurologie

Nantes, France

Location

CHU de Nice - service de neurologie

Nice, France

Location

CHU de Nîmes - service de neurologie

Nîmes, France

Location

AP-HP - Hôpital La Pitié Salpétrière - service de neurologie

Paris, France

Location

AP-HP - Hôpital Saint-Antoine - service de neurologie

Paris, France

Location

Fondation Rothschild - service de neurologie

Paris, France

Location

CHU de Poitiers - service de neurologie

Poitiers, France

Location

CHU de Rennes - service de neurologie

Rennes, France

Location

CHU de Rouen - service de neurologie

Rouen, France

Location

CH de Saint-Denis - service de neurologie

Saint-Denis, France

Location

CHU d'Amiens - service de neurologie

Salouël, France

Location

CHRU de Strasbourg - service de neurologie

Strasbourg, France

Location

CHU de Toulouse - service de neurologie

Toulouse, France

Location

CHU de Tours - service de neurologie

Tours, France

Location

CHU de Fort de France - service de neurologie

Fort-de-France, Martinique

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Aurélie RUET, Prof

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: January 27, 2022
• Study Start: June 20, 2022
• Primary Completion: December 22, 2023
• Study Completion: December 22, 2023
• Last Updated: January 16, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1); FR (26)