Leflunomide - Medication and Pregnancy KB

Leflunomide

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Chambers (Unexposed control, disease free), 2010	USA and Canada 1999 - 2009	Participants in the study were recruited from the pregnant callers to OTIS counseling services, and from direct marketing to rheumatologists through mail, professional meetings, and the OTIS Web site.	Pregnant women with a diagnosis of rheumatoid arthritis (RA) or juvenile rheumatoid arthritis (JRA) who took at least one dose of leflunomide (for any length of time) during the first trimester of pregnancy.	unexposed, disease free A comparison group of healthy pregnant women without a diagnosis of RA, JRA, or any other autoimmune disease, including type 1 or type 2 diabetes mellitus, and without exposure to any known human teratogen, including isotretinoin, anticonvulsants, and large quantities of alcohol.	64 / 78	2 OTIS articles NOT the same data. Cassina 2012 included women which did not meet the strict criteria of Chambers 2010 (enrolled > 20 GW, indication other than RA, or LEF discontinued within 2 years prior to conception but no elimination confirmation).
Chambers (Unexposed control, sick), 2010	USA and Canada 1999 - 2009	Participants in the study were recruited from the pregnant callers to OTIS counseling services, and from direct marketing to rheumatologists through mail, professional meetings, and the OTIS Web site.	Pregnant women with a diagnosis of rheumatoid arthritis (RA) or juvenile rheumatoid arthritis (JRA) who took at least one dose of leflunomide (for any length of time) during the first trimester of pregnancy.	unexposed, sick A disease-matched comparison group of pregnant women with a diagnosis of RA or JRA who did not take leflunomide at any time during pregnancy and did not have exposure to any other known teratogenic agent.	64 / 108	2 OTIS articles NOT the same data. Cassina 2012 included women which did not meet the strict criteria of Chambers 2010 (enrolled > 20 GW, indication other than RA, or LEF discontinued within 2 years prior to conception but no elimination confirmation)
Karadag, 2013	Turkey 2004 - 2012	Patients who used leflunomide before or during pregnancy.	Female patients whose leflunomide was interrupted after detection of pregnancy.	unexposed, sick Female patients whose leflunomide was interrupted before pregnancy.	3 / 13
Langen, 2014	USA 2001 - 2009	All pregnancies complicated by Rheumatoid arthritis (RA) delivered at the institution.	Women with leflunomide near the time of conception. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Women with prednisone only near the time of conception. (This is a subgroup of exposure among the whole exposed group considered in the study).	2 / 15	Leflunomide was discontinued in the 2 pregnancies upon discovery of pregnancy.
Viktil (Controls exposed to other treatments), 2012	Norway 2004 - 2007	Singleton pregnancies in women receiving at least 1 prescription during the study period.	Women with dispensation of Leflunomide from 3 months prior to pregnancy to delivery (subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Women with dispensation of other anti-rheumatic drugs (Prednisolone, NSAIDs, Sulfasalazine, Hydroxychloroquine, Etanercept, Adalimumab, Methotrexate, Leflunomid, or Anakinra) from 3 months prior to pregnancy to delivery.	2 / 1459	Analysis performed on anti-rheumatic drugs as a whole, no individual analyse for each substance. Raw data (number of exposed pregnancies and malformations) were available in the text and were used for this meta-analysis.
Viktil (Controls unexposed, NOS), 2012	Norway 2004 - 2007	Singleton pregnancies in women receiving at least 1 prescription during the study period.	Women with dispensation of Leflunomide from 3 months prior to pregnancy to delivery (subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Singleton pregnancies whose mothers did not received an anti-rheumatic drugs in the period 3 months prior to conception until labour.	2 / 154976	Analysis performed on anti-rheumatic drugs as a whole, no individual analyse for each substance. Raw data (number of exposed pregnancies and malformations) were available in the text and were used for this meta-analysis.

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk
Bérard, 2018	Canada 1998 - 2015	Spontaneous abortions (before the 22nd GW) or Singleton liveborns with malformations (exclusion of minor and chromosomal abnormalities) or prematurity (<37th GW) or LBW (<2500g).	Pregnancies ending without the considered adverse outcome.	14368 / 129948	Within the study cohort, 4 separate case–control analyses were conducted. Analyses of spontaneous abortions: all pregnancies; analyses of malformations, prematurity and LBW: only singleton liveborns. 1st trimester: 0–14 completed weeks of gestation.

master protocol