An Observational Study to Learn About the Interferon-beta Exposure of Pregnant Women During the Second and Third Trimester in Finland and Sweden

NCT06053749 | Active Not Recruiting

• 2 other identifiers: 21334EUPAS38736
• Study Type: observational
• Target: 4
• Locations: 2 countries
• Sites: 2

Brief Summary

Observational data have suggested no increased risk of adverse pregnancy outcomes associated with exposure to interferon-beta (IFNB) before or during pregnancy. After the emergence of these data, the European Medicines Agency approved a label change for IFNB in September 2019, stating that use of IFNB during pregnancy may be considered, if clinically needed. However, limited data on pregnancies exposed in the 2nd and 3rd trimesters were observed. INFORM is a secondary use of data drug utilisation study (DUS) to determine late pregnancy exposure (i.e. during the 2nd and 3rd trimester) to IFNB in Finland and Sweden, which will inform whether the number of exposed pregnancies is adequate to conduct a cohort study on adverse pregnancy outcomes, with a focus on late pregnancy exposure. The number of pregnancies will be initially reported three years after the revised label implementation (September 2019) and will include data on pregnancies from 1996 in Finland and from 2005 in Sweden up through 31 December 2022. If the number of pregnancies is deemed adequate for conducting the cohort study on adverse pregnancy outcomes, this DUS will be finalised with the drug utilisation data accrued up through 31 December 2022. If the number of pregnancies until 31 December 2022 is deemed inadequate, this study may be continued and the primary and secondary objectives may be examined five years after the revised label implementation, including pregnancies until 31 December 2024.

Conditions

Multiple Sclerosis (MS)

Outcome Measures

Primary Outcomes (3)

• The number of pregnancies of women with MS, not allowing exposure to other MS Disease Modifying Drugs (MSDMDs)

  Analysis groups: Pregnancies exposed to IFNB only group and Pregnancies unexposed to IFNB nor other MSDMDs group

  Data recorded between 01 January 1996 - 31 December 2022 in Finland, and 01 July 2005 - 31 December 2022 in Sweden.

• The level of precision for the risk of pre-defined adverse pregnancy outcomes in late pregnancy that can be obtained with the available number of exposed and unexposed pregnancies

  Pre-defined adverse pregnancy outcomes: * Anomalies: Major congenital anomalies (MCA); All anomalies, including minor and major * Fatal outcomes: Spontaneous abortions, Elective terminations, Stillbirth and Neonatal mortality * Growth outcomes: Small for gestation age and Low birth weight * Other outcomes: Preterm birth Late pregnancy, i.e. the 2nd and 3rd trimester.

  Data recorded between 01 January 1996 - 31 December 2022 in Finland, and 01 July 2005 - 31 December 2022 in Sweden.

• The annual number of pregnancies of women with MS in the exposure groups

  Analysis in Pregnancies exposed to IFNB only group.

  Data recorded between 2015-2019 and 2020-2022.

Secondary Outcomes (2)

• The number of pregnancies of women with MS in Finland and Sweden in exposure groups allowing exposure to other MSDMDs

  Data recorded between 01 January 1996 - 31 December 2022 in Finland, and 01 July 2005 - 31 December 2022 in Sweden.

• The annual number of women with MS in childbearing age, and with dispensed IFNB

  Data recorded between 2015 to 2022 in Finland and Sweden

Study Arms (4)

Pregnancies exposed to IFNB only

With dispensed IFNB, no other MS disease modifying drugs (MSDMDs) during the pre-pregnancy period or during pregnancy

Drug: Avonex (IFNβ-1-a, Biogen Netherlands B.V); Drug: Rebif (IFNβ-1-a, Merck Europe B.V.); Drug: Extavia (IFNβ-1-b, Novartis Europharm Limited); Drug: Betaseron (IFN-β-1-b, BAY86-5046, Bayer AG); Drug: Plegridy (Peg IFNβ-1-a, Biogen Netherlands B.V)

Pregnancies unexposed to IFNB nor other MSDMDs

No dispensed IFNB nor any other MSDMDs during the pre-pregnancy period nor any time during pregnancy

Pregnancies exposed to IFNB (regardless of other MSDMDs)

With dispensed IFNB, regardless of other MS disease modifying drugs (MSDMDs) during the pre-pregnancy period or during pregnancy

Drug: Avonex (IFNβ-1-a, Biogen Netherlands B.V); Drug: Rebif (IFNβ-1-a, Merck Europe B.V.); Drug: Extavia (IFNβ-1-b, Novartis Europharm Limited); Drug: Betaseron (IFN-β-1-b, BAY86-5046, Bayer AG); Drug: Plegridy (Peg IFNβ-1-a, Biogen Netherlands B.V); Drug: MS disease modifying drugs (MSDMDs)

Pregnancies unexposed to IFNB (regardless of other MSDMDs)

No dispensed IFNB during the pre-pregnancy period nor any time during pregnancy, regardless of other MSDMDs Outcomes:

Drug: MS disease modifying drugs (MSDMDs)

Interventions

Avonex (IFNβ-1-a, Biogen Netherlands B.V) DRUG

Information on drug use in hospitals and outpatient clinics are not recorded in the drug registers used in the study and, thus, information on exposure to these medications is not available.

Pregnancies exposed to IFNB (regardless of other MSDMDs); Pregnancies exposed to IFNB only

Rebif (IFNβ-1-a, Merck Europe B.V.) DRUG

Information on drug use in hospitals and outpatient clinics are not recorded in the drug registers used in the study and, thus, information on exposure to these medications is not available.

Pregnancies exposed to IFNB (regardless of other MSDMDs); Pregnancies exposed to IFNB only

Betaseron (IFN-β-1-b, BAY86-5046, Bayer AG) DRUG

Information on drug use in hospitals and outpatient clinics are not recorded in the drug registers used in the study and, thus, information on exposure to these medications is not available.

Pregnancies exposed to IFNB (regardless of other MSDMDs); Pregnancies exposed to IFNB only

MS disease modifying drugs (MSDMDs) DRUG

Information on drug use in hospitals and outpatient clinics are not recorded in the drug registers used in the study and, thus, information on exposure to these medications is not available.

Pregnancies exposed to IFNB (regardless of other MSDMDs); Pregnancies unexposed to IFNB (regardless of other MSDMDs)

Extavia (IFNβ-1-b, Novartis Europharm Limited) DRUG

Information on drug use in hospitals and outpatient clinics are not recorded in the drug registers used in the study and, thus, information on exposure to these medications is not available.

Pregnancies exposed to IFNB (regardless of other MSDMDs); Pregnancies exposed to IFNB only

Plegridy (Peg IFNβ-1-a, Biogen Netherlands B.V) DRUG

Information on drug use in hospitals and outpatient clinics are not recorded in the drug registers used in the study and, thus, information on exposure to these medications is not available.

Pregnancies exposed to IFNB (regardless of other MSDMDs); Pregnancies exposed to IFNB only

Eligibility Criteria

• Age: 12 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Aggregate secondary data will be collected from the following national registers in Finland and Sweden. FINLAND: Medical Birth Register (MBR-Fin), Care Register for Health Care, National Reimbursement Register/National Prescription Register, Register of Induced Abortions. SWEDEN: Medical Birth Register (MBR-Swe), National Patient Register (NPR), Swedish Prescribed Drug Register (SPDR).

You may qualify if:

• Women with a diagnosis of MS disease, regardless of MS clinical type, recorded at least once during the full study period.
• Women with at least one recorded pregnancy after the MS diagnosis (including pregnancies ending in live birth, stillbirth, spontaneous abortion, ectopic pregnancy, or elective termination)

You may not qualify if:

• \- None.

Sponsors & Collaborators

• Bayer: lead
• Biogen Netherlands B.V: collaborator
• Merck Europe B.V.: collaborator
• Novartis Europharm Limited: collaborator

Study Sites (2)

Many locations

Multiple Locations, Finland

Location

Many locations

Multiple Locations, Sweden

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Interferon beta-1a; Interferon beta-1b; peginterferon beta-1a

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)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Design

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

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: September 26, 2023
• Study Start: March 20, 2024
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); FI (1)