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

INFORM - Interferon-Beta Exposure in the 2nd and 3rd Trimester of Pregnancy - a Register-Based Drug Utilisation Study in Finland and Sweden

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis (MS)
• Intervention / Treatment: 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)

• Study Type: Observational
• Enrollment (Actual): 4

Contacts and Locations

Study Locations

• Finland
  • Multiple Locations, Finland
    • Many Locations
• Sweden
  • Multiple Locations, Sweden
    • Many Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• 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).

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

- None.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of pregnancies of women with MS in Finland and Sweden in exposure groups allowing exposure to other MSDMDs	Analysis groups: Pregnancies exposed to IFNB (regardless of other MSDMDs) group and Pregnancies unexposed to IFNB (regardless of other MSDMDs) group	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

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Biogen Netherlands B.V; Novartis Europharm Limited; Merck Europe B.V.

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: September 19, 2023
• First Submitted That Met QC Criteria: September 19, 2023
• First Posted (Actual): September 26, 2023

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Intercellular Signaling Peptides and Proteins; Cytokines; Interferon Type I; Interferons; Interferon-beta; Interferon beta-1a; Interferon beta-1b; peginterferon beta-1a
• Other Study ID Numbers: 21334; EUPAS38736 (Other Identifier: ENCEPP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No data will be shared

Drug and device information, study documents

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