EPID Multiple Sclerosis Pregnancy Study

Pregnancy Outcomes in Multiple Sclerosis Populations Exposed and Unexposed to Interferon β - a Register-based Study in the Nordic Countries

Multiple Sclerosis (MS) is the most common chronic neurologic disability in young adult females in their childbearing ages. Little evidence is available regarding the association between exposure to IFN-beta (β) products and adverse pregnancy outcomes. Therefore the four marketing holders of IFN-β are conducting a European-wide IFN-β pregnancy registry. Additionally, the Committee for Medicinal Products for Human Use (CHMP) has requested a study to enable identification of pregnancy outcomes in the MS population unexposed to IFN-β products for comparison with the ongoing European IFN-β Pregnancy Registry.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Betaseron (Interferon beta-1b, BAY86-5046), Bayer HealthCare AG; Drug: Extavia (interferon beta-1b), Novartis Pharma AG; Drug: Rebif (interferon beta-1a), Merck Serono Europe Ltd; Drug: Plegridy (peginterferon beta-1a), Biogen Idec Ltd; Drug: Avonex (interferon beta-1a), Biogen Idec Ltd; Drug: MSDMDs other than Betaseron (Interferon beta-1b, BAY86-5046); Other: No MSDMDs therapy (control)

Detailed Description

Information will be obtained from the Drugs and Pregnancy Project database (DPP - FIN) and the Medical Birth Register (MBR - SWE, NOR). The Finnish DPP and Norwegian MBR include information on all stillbirths of foetuses with a birth weight of at least 500 g or with a gestational age of at least 22+0 Gestational Week (GW). The Swedish MBR includes data on stillbirths after 28 GW

The estimated number of pregnancies in MS patients needed is 1671, encompassing data from:

i) FIN: 1 January 1996 - 31 December 2014; ii) SWE: 1 July 2005 - 31 December 2014; iii) NOR: 1 January 2004 - 31 December 2014.

• Study Type: Observational
• Enrollment (Actual): 2089

Contacts and Locations

Study Locations

• Finland
  • Multiple Locations, Finland
    • Many Locations

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The target study population consists of Finnish, Swedish and Norwegian women diagnosed with MS who have been pregnant during the study period from 1996 to 2014. The pregnancy may have resulted in an induced abortion, spontaneous abortion, ectopic pregnancy, stillbirth, or live birth during the study period.

Description

Inclusion Criteria:

• Women who have had a pregnancy with a recorded outcome consisting of an induced abortion, spontaneous abortion, ectopic pregnancy, or birth during the study period in FIN, SWE or NOR with the event being documented in the relevant databases.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
IFN-β / Cohort 1; Exposure to IFN-β only	Drug: Betaseron (Interferon beta-1b, BAY86-5046), Bayer HealthCare AG; Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR); Drug: Extavia (interferon beta-1b), Novartis Pharma AG; Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR); Drug: Rebif (interferon beta-1a), Merck Serono Europe Ltd; Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR); Drug: Plegridy (peginterferon beta-1a), Biogen Idec Ltd; Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR); Drug: Avonex (interferon beta-1a), Biogen Idec Ltd; Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR)
IFN-β + other MSDMDs / Cohort 2; Women with MS exposed to IFN-β regardless of exposure to other MSDMDs	Drug: Betaseron (Interferon beta-1b, BAY86-5046), Bayer HealthCare AG; Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR); Drug: Extavia (interferon beta-1b), Novartis Pharma AG; Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR); Drug: Rebif (interferon beta-1a), Merck Serono Europe Ltd; Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR); Drug: Avonex (interferon beta-1a), Biogen Idec Ltd; Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR); Drug: MSDMDs other than Betaseron (Interferon beta-1b, BAY86-5046); Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR)
No MSDMDs / Cohort 3; Women with MS exposed with no exposure to any MSDMDs	Other: No MSDMDs therapy (control); Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR)
No IFN-β + other MSDMDs / Cohort 4; Women with MS exposed to IFN-β exposure regardless of exposure to other MSDMDs	Drug: MSDMDs other than Betaseron (Interferon beta-1b, BAY86-5046); Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR)
Other MSDMDs / Cohort 5; Women with MS exposed to other MSDMD only excluding IFN-β or glatiramer acetate (Copaxone) or dimethyl fumarate (Tecfidera)	Drug: MSDMDs other than Betaseron (Interferon beta-1b, BAY86-5046); Information will be obtained from the databses DPP (FIN) and MBR (SWE, NOR)
Control / Cohort 6; Women from the general population without MS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse pregnancy outcome due to different regimes of IFN-β exposure defined as a composite endpoint including presence of elective Termination of Pregnancy due to Foetal Anomaly (TOPFA), Major Congenital Anomaly (MCA) or stillbirth	Cohort 1: Exposure to IFN-β only Cohort 2: All patients with IFN-β exposure regardless of exposure to other MS Disease Modifying Drug (MSDMDs) Cohort 3: No exposure to any MSDMDs Cohort 4: All patients with no IFN-β exposure regardless of exposure to other MSDMDs	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Elective TOPFA for other reasons than IFN-β exposure	Cohort 1: Exposure to IFN-β only Cohort 2: All patients with IFN-β exposure regardless of exposure to other MS Disease Modifying Drug (MSDMDs) Cohort 3: No exposure to any MSDMDs Cohort 4: All patients with no IFN-β exposure regardless of exposure to other MSDMDs	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Elective termination for other reasonsthan IFN-β exposure	Cohort 1: Exposure to IFN-β only Cohort 2: All patients with IFN-β exposure regardless of exposure to other MS Disease Modifying Drug (MSDMDs) Cohort 3: No exposure to any MSDMDs Cohort 4: All patients with no IFN-β exposure regardless of exposure to other MSDMDs	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Stillbirth due to different regimes of IFN-β exposure	Cohort 1: Exposure to IFN-β only Cohort 2: All patients with IFN-β exposure regardless of exposure to other MS Disease Modifying Drug (MSDMDs) Cohort 3: No exposure to any MSDMDs Cohort 4: All patients with no IFN-β exposure regardless of exposure to other MSDMDs	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Live birth while different regimes of IFN-β exposure	Cohort 1: Exposure to IFN-β only Cohort 2: All patients with IFN-β exposure regardless of exposure to other MS Disease Modifying Drug (MSDMDs) Cohort 3: No exposure to any MSDMDs Cohort 4: All patients with no IFN-β exposure regardless of exposure to other MSDMDs	Retrospective Data analysis: MS patients data encompassing approximately 19 years
MCA due to different regimes of IFN-β exposure	Cohort 1: Exposure to IFN-β only Cohort 2: All patients with IFN-β exposure regardless of exposure to other MS Disease Modifying Drug (MSDMDs) Cohort 3: No exposure to any MSDMDs Cohort 4: All patients with no IFN-β exposure regardless of exposure to other MSDMDs	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Comparison of the prevalence of serious adverse pregnancy outcome due to different regimes of IFN-β exposure defined as a composite endpoint including elective TOPFA, MCA or stillbirth	Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Comparison of the prevalence of elective termination for other reasons than due to different regimes of IFN-β exposure	Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Comparison of the prevalence of stillbirth due to different regimes of IFN-β exposure	Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Comparison of the prevalence of live birth due to different regimes of IFN-β exposure	Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Comparison of the prevalence of MCA due to different regimes of IFN-β exposure	Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Comparison of the prevalence of Elective TOPFA due to different regimes of IFN-β exposure	Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)	Retrospective Data analysis: MS patients data encompassing approximately 19 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the prevalence of ectopic pregnancies due to different regimes of IFN-β exposure	Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3),; Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4); Women with MS exposed to IFN-β regardless of exposure to other MSDMDs (cohort 2) vs. unexposed to any MSDMDs (cohort 3)	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Comparison of the prevalence of spontaneous abortions due to different regimes of IFN-β exposure	Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3),; Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4); Women with MS exposed to IFN-β regardless of exposure to other MSDMDs (cohort 2) vs. unexposed to any MSDMDs (cohort 3)	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Prevalence of elective TOPFA stratified by specific patient characteristics	Patient characteristics: country, year of pregnancy outcome, chronic diseases, exposure to any teratogenic medications, time since MS diagnosis, duration of MS treatment, maternal age, gestational age, weight of the newborn	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Prevalence of stillbirth stratified by specific patient characteristics	Patient characteristics: country, year of pregnancy outcome, chronic diseases, exposure to any teratogenic medications, time since MS diagnosis, duration of MS treatment, maternal age, gestational age, weight of the newborn	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Prevalence of live birth stratified by specific patient characteristics	Patient characteristics: country, year of pregnancy outcome, chronic diseases, exposure to any teratogenic medications, time since MS diagnosis, duration of MS treatment, maternal age, gestational age, weight of the newborn	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Prevalence of MCA stratified by specific patient characteristics	Patient characteristics: country, year of pregnancy outcome, chronic diseases, exposure to any teratogenic medications, time since MS diagnosis, duration of MS treatment, maternal age, gestational age, weight of the newborn	Retrospective Data analysis: MS patients data encompassing approximately 19 years
Comparison of the prevalence of ectopic pregnancies due to different regimes of IFN-β exposure	Patient characteristics: country, year of pregnancy outcome, chronic diseases, exposure to any teratogenic medications, time since MS diagnosis, duration of MS treatment, maternal age, gestational age, weight of the newborn	Retrospective Data analysis: MS patients data encompassing approximately 19 years

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Novartis Pharmaceuticals; Biogen; EPID Research; Merck Serono Europe Ltd

Publications and helpful links

Helpful Links

• Click here to find results for studies related to Bayer products.

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2016
• Primary Completion (Actual): August 14, 2018
• Study Completion (Actual): August 14, 2018

Study Registration Dates

• First Submitted: April 20, 2016
• First Submitted That Met QC Criteria: April 20, 2016
• First Posted (Estimate): April 25, 2016

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferons; Interferon beta-1a; Interferon-beta; Interferon beta-1b
• Other Study ID Numbers: 18219