Study identification

PURI

https://redirect.ema.europa.eu/resource/28099

EU PAS number

EUPAS2566

Study ID

28099

Official title and acronym

Pregnancy outcome after rheumatologic methotrexate (MTX) treatment prior to or during early pregnancy: a prospective multicenter cohort study (Rheumatologic MTX treatment and pregnancy outcome)

DARWIN EU® study

No

Study countries

Canada
Finland
France
Germany
Israel
Italy
Netherlands
Switzerland
United States

Study description

Methotrexate (MTX) is known as a teratogen that causes a specific embryopathy. This is based on several retrospective case reports (e.g. Seidahmed 2006, Yedlinski 2005, Adam 2003, Chapa 2003, Krähenmann 2002, Wheeler 2002, Bawle 1998, and Milunsky 1968.). MTX has been used as an abortifacient, in cancer therapy, and beginning in the 90th for rheumatoid arthritis and some autoimmune diseases. The dose of MTX varies depending on the treatment indication and is lower in rheumatic diseases. There is still uncertainty concerning the risk of low-dose methotrexate therapy during pregnancy. As there is only one small prospective study, which observed no major birth defects in 28 pregnancies (Lewden 2004), no precise risk evaluation can be made so far. Furthermore, it has been debated how long prior to conception MTX therapy should be stopped. Recently, a broad international panel of rheumatologists recommended stopping MTX at least 3 months before conception (Visser 2009). Study Target: To assess the risk of low-dose MTX exposure in early pregnancy. Primary Outcome:Rate of major birth defects, rate of specific MTX embryopathy (time frame up to approximately 8 weeks after birth), rate of spontaneous abortion, intrauterine growth retardation (IUGR) in malformed and non malformed newborns (criterion: birth weigth), rate of prematurity. There are three prospectively ascertained groups to be compared:1) Exposed group with maternal exposure of low-dose MTX for rheumatic/autoimmune diseases, 2) Control group 1 (“disease group”): Pregnant women with rheumatic /autoimmune diseases without MTX during pregnancy, 3) Non-exposed control group 2 (“general control”): No MTX, no rheumatic / autoimmune diseases.

Study status

Finalised
Research institutions and networks

Institutions

Networks

Contact details

Corinna Weber-Schoendorfer

Primary lead investigator
Study timelines

Date when funding contract was signed

Actual:

Study start date

Actual:

Data analysis start date

Actual:

Date of final study report

Planned:
Actual:
Sources of funding
Other

More details on funding

Bundesministerium für Gesundheit, Senatsverwaltung Berlin
Study protocol
Initial protocol

Arthritis Rheumatol_abstract

English (145.4 KB - PDF)View document
Regulatory

Was the study required by a regulatory body?

No

Is the study required by a Risk Management Plan (RMP)?

Not applicable