EPID Multiple Sclerosis Pregnancy Study

Completed

• Conditions: Multiple Sclerosis
• Interventions: Drug: Betaseron (Interferon beta-1b, BAY86-5046), Bayer HealthCare AG; Other: No MSDMDs therapy (control); 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: MSDMDs other than Betaseron (Interferon beta-1b, BAY86-5046); Drug: Avonex (interferon beta-1a), Biogen Idec Ltd

• Registration Number: NCT02749396
• Lead Sponsor: Bayer

Brief Summary

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.

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 Timeline

• Study First Submitted: 2016-04-20
• Study First Submitted QC: 2016-04-20
• Study First Posted: 2016-04-25
• Study Start: 2016-05-02
• Primary Completion: 2018-08-14
• Study Completion: 2018-08-14
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-12
• Last Update Posted: 2019-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 2089

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.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
IFN-β / Cohort 1	Betaseron (Interferon beta-1b, BAY86-5046), Bayer HealthCare AG	Exposure to IFN-β only
IFN-β / Cohort 1	Extavia (interferon beta-1b), Novartis Pharma AG	Exposure to IFN-β only
IFN-β / Cohort 1	Rebif (interferon beta-1a), Merck Serono Europe Ltd	Exposure to IFN-β only
IFN-β / Cohort 1	Plegridy (peginterferon beta-1a), Biogen Idec Ltd	Exposure to IFN-β only
IFN-β + other MSDMDs / Cohort 2	Rebif (interferon beta-1a), Merck Serono Europe Ltd	Women with MS exposed to IFN-β regardless of exposure to other MSDMDs
IFN-β + other MSDMDs / Cohort 2	Betaseron (Interferon beta-1b, BAY86-5046), Bayer HealthCare AG	Women with MS exposed to IFN-β regardless of exposure to other MSDMDs
IFN-β + other MSDMDs / Cohort 2	Extavia (interferon beta-1b), Novartis Pharma AG	Women with MS exposed to IFN-β regardless of exposure to other MSDMDs
IFN-β + other MSDMDs / Cohort 2	MSDMDs other than Betaseron (Interferon beta-1b, BAY86-5046)	Women with MS exposed to IFN-β regardless of exposure to other MSDMDs
No MSDMDs / Cohort 3	No MSDMDs therapy (control)	Women with MS exposed with no exposure to any MSDMDs
No IFN-β + other MSDMDs / Cohort 4	MSDMDs other than Betaseron (Interferon beta-1b, BAY86-5046)	Women with MS exposed to IFN-β exposure regardless of exposure to other MSDMDs
IFN-β / Cohort 1	Avonex (interferon beta-1a), Biogen Idec Ltd	Exposure to IFN-β only
Other MSDMDs / Cohort 5	MSDMDs other than Betaseron (Interferon beta-1b, BAY86-5046)	Women with MS exposed to other MSDMD only excluding IFN-β or glatiramer acetate (Copaxone) or dimethyl fumarate (Tecfidera)
IFN-β + other MSDMDs / Cohort 2	Avonex (interferon beta-1a), Biogen Idec Ltd	Women with MS exposed to IFN-β regardless of exposure to other MSDMDs

Primary Outcome Measures

Name	Time	Method
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	Retrospective Data analysis: MS patients data encompassing approximately 19 years	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
Elective TOPFA for other reasons than IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	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
Elective termination for other reasonsthan IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	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
Stillbirth due to different regimes of IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	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
Live birth while different regimes of IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	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
Comparison of the prevalence of stillbirth due to different regimes of IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	1. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; 2. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)
Comparison of the prevalence of live birth due to different regimes of IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	1. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; 2. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)
Comparison of the prevalence of MCA due to different regimes of IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	1. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; 2. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)
Comparison of the prevalence of Elective TOPFA due to different regimes of IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	1. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; 2. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)
MCA due to different regimes of IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	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
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	Retrospective Data analysis: MS patients data encompassing approximately 19 years	1. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; 2. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)
Comparison of the prevalence of elective termination for other reasons than due to different regimes of IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	1. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3) and; 2. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4)

Secondary Outcome Measures

Name	Time	Method
Prevalence of stillbirth stratified by specific patient characteristics	Retrospective Data analysis: MS patients data encompassing approximately 19 years	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
Comparison of the prevalence of ectopic pregnancies due to different regimes of IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	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
Prevalence of live birth stratified by specific patient characteristics	Retrospective Data analysis: MS patients data encompassing approximately 19 years	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
Comparison of the prevalence of spontaneous abortions due to different regimes of IFN-β exposure	Retrospective Data analysis: MS patients data encompassing approximately 19 years	1. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to any MSDMDs (cohort 3),; 2. Women with MS exposed to IFN-β only (cohort 1) vs. unexposed to IFN-β regardless of exposure to other MSDMDs (cohort 4); 3. Women with MS exposed to IFN-β regardless of exposure to other MSDMDs (cohort 2) vs. unexposed to any MSDMDs (cohort 3)
Prevalence of MCA stratified by specific patient characteristics	Retrospective Data analysis: MS patients data encompassing approximately 19 years	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
Prevalence of elective TOPFA stratified by specific patient characteristics	Retrospective Data analysis: MS patients data encompassing approximately 19 years	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

Trial Locations

Locations (1)

Many locations; 🇫🇮 Multiple Locations, Finland