Safety of Exposure to Natalizumab During Pregnancy (BABYZUMAB-2)

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Behavioral: Questionnaire

• Study Type: Observational
• Enrollment (Actual): 68

Contacts and Locations

• Study Contact: Name: Mathilde DELOIRE, PhD; Phone Number: +33 (0)5.57.82.12.75; Email: mathilde.deloire@chu-bordeaux.fr
• Study Contact Backup: Name: Aurélie RUET, Prof; Phone Number: +33 (0)5.56.79.55.21; Email: aurelie.ruet@chu-bordeaux.fr

Study Locations

• France
  • Besançon, France
    • CHRU de Besançon - service de neurologie
  • Bordeaux, France
    • CHU de Bordeaux - Service de neurologie
  • Bron, France
    • HCL - service de neurologie
  • Corbeil-Essonnes, France
    • CH Sud Francilien - service de neurologie
  • Créteil, France
    • AP-HP - Hôpital de Créteil - service de neurologie
  • Dijon, France
    • CHU de Dijon-Bourgogne
  • La Tronche, France
    • CHU de Grenoble-Alpes
  • Lille, France
    • CHRU de Lille - service de neurologie
  • Limoges, France
    • CHU de Limoges - service de neurologie
  • Marseille, France
    • AP-HM - service de neurologie
  • Montpellier, France
    • CHU de Montpellier - Service de neurologie
  • Nancy, France
    • CHRU de Nancy - service de neurologie
  • Nantes, France
    • CHU de Nantes - service de neurologie
  • Nice, France
    • CHU de Nice - service de neurologie
  • Nîmes, France
    • CHU de Nîmes - service de neurologie
  • Paris, France
    • AP-HP - Hôpital La Pitié Salpétrière - service de neurologie
  • Paris, France
    • AP-HP - Hôpital Saint-Antoine - service de neurologie
  • Paris, France
    • Fondation Rothschild - service de neurologie
  • Poitiers, France
    • CHU de Poitiers - service de neurologie
  • Rennes, France
    • CHU de Rennes - service de neurologie
  • Rouen, France
    • CHU de Rouen - service de neurologie
  • Saint-Denis, France
    • CH de Saint-Denis - service de neurologie
  • Salouël, France
    • CHU d'Amiens - service de neurologie
  • Strasbourg, France
    • CHRU de Strasbourg - service de neurologie
  • Toulouse, France
    • CHU de Toulouse - service de neurologie
  • Tours, France
    • CHU de Tours - service de neurologie
• Martinique
  • Fort-de-France, Martinique
    • CHU de Fort de France - service de neurologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; continuation of NTZ throughout pregnancy and postpartum	Behavioral: Questionnaire; Questionnaire
Group 2; exposure during the first trimester	Behavioral: Questionnaire; Questionnaire
Group 3; exposure during the first and the second trimester	Behavioral: Questionnaire; Questionnaire

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: Biogen
• Investigators: Principal Investigator: Aurélie RUET, Prof, CHU Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2022
• Primary Completion (Actual): December 22, 2023
• Study Completion (Actual): December 22, 2023

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 27, 2022

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Safety; pregnancy; Natalizumab
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis
• Other Study ID Numbers: CHUBX 2020/65

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No