Adalimumab

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Broms (Controls exposed to other treatments), 2020	Denmark, Finland and Sweden 2006 - 2013	All women who gave birth to a singleton infant during the study period.	Women who filled prescriptions for Adalimumab within 90 days before their LMP until delivery. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Women who filled prescriptions for Nonbiologic systemic treatment (mainly azathioprine, corticosteroids, sulfasalazine, anti-malarials, and methotrexate) within 90 days before their LMP until delivery.	257 / 9393
Broms (Controls unexposed, disease free), 2020	Denmark, Finland and Sweden 2006 - 2013	All women who gave birth to a singleton infant during the study period.	Women who filled prescriptions for Adalimumab within 90 days before their LMP until delivery. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free The general population (women without the diseases of interest and without treatment).	257 / 1623483
Bröms (controls unexposed, disease free), 2016	Denmark and Sweden 2004/6 - 2012	Women and their infants up to 1 year of age (among all 15 million residents of Denmark and Sweden).	Women who had filled prescriptions for adalimumab within 90 days before and 90 days after their last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Women without disease or TNF treatment (ie, the general population).	161 / 1250192	Primary analyse on Anti-TNF, with individual result by substance (n=161 ADA).
Bröms (controls unexposed, sick), 2016	Denmark and Sweden 2004/6 - 2012	Women and their infants up to 1 year of age (among all 15 million residents of Denmark and Sweden).	Women who had filled prescriptions for adalimumab within 90 days before and 90 days after their last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Women with chronic inflammatory disease but no anti-TNF treatment.	161 / 21549	Primary analyse on Anti-TNF, with individual result by substance (n=161 ADA). Controls: Corticosteroids (7.7%); anti-inflammatory treatments (20.8%: AZA, mercaptopurine, cyclosporine, acitretin, mycophenolate...); MTX (0.2%).
Casanova, 2013	Spain Not specified	All women who had become pregnant after the diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) followed in the IBD Units from 24 Spanish hospitals.	Pregnancies in IBD patients on adalimumab during pregnancy or during the 3 months before conception. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Pregnancies in IBD patients which did not receive thiopurines or anti-TNF-α drugs either during pregnancy or the 3 months before conception. (84% exposed to 5-Aminosalicylates and/or steroids).	16 / 318	Primary aim: evaluate the safety of thiopurines and anti-TNF-α during conception and pregnancy in IBD patients. Exposed population divided in 2 groups: A) thiopurines alone; B) anti-TNF-α drugs (IFX, ADA, and CZB) with or without concomitant thiopurines.
Chambers (Controls unexposed, disease free), 2019	USA and Canada 2004 - 2016	Pregnant women and their health care providers who contact the services with questions about the risks of exposures in pregnancy.	Pregnant women with a diagnosis of rheumatoid arthritis or Crohn’s Disease who received at least one dose of adalimumab in the first trimester.	unexposed, disease free Pregnant women have a rheumatic disease or an inflammatory bowel disease, no treatment with a monoclonal antibody medication in pregnancy.	257 / 225
Chambers (Controls, sick), 2019	USA and Canada 2004 - 2016	Pregnant women and their health care providers who contact the services with questions about the risks of exposures in pregnancy.	Pregnant women with a diagnosis of rheumatoid arthritis or Crohn’s Disease who received at least one dose of adalimumab in the first trimester.	unexposed, sick Pregnant women with a diagnosis of rheumatoid arthritis or Crohn’s Disease who not used adalimumab at any time during pregnancy.	257 / 120	Unexposed group: exposure to another anti-TNF-α medication:18/120 (15%). Sensitivity analyse excluding women from the disease-matched unexposed group with anti-TNF-α medication in pregnancy, produced similar results (data not shown).
De Lorenzo (Controls unexposed, disease free), 2020	Italy 2009 - 2017	Mothers who attended the Clinic.	Children born to mothers with autoimmune diseases on Adalimumab therapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Children born to healthy mothers.	2 / 36
De Lorenzo (Controls unexposed, sick), 2020	Italy 2009 - 2017	Mothers who attended the Clinic.	Children born to mothers with autoimmune diseases on Adalimumab therapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Children born to mothers with autoimmune diseases not treated with Biologic disease-modifying anti-rheumatic drugs (bDMARDs).	2 / 32	Unexposed: 13 of 32 neonates were born to mothers under no immunosuppressive, 15 to HCQ, 1 to AZA and 3 to both AZA and HCQ.
Hoxha, 2017	Italia 2008 - 2015	Patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis attending four Rheumatology Units.	Pregnancies in patients which were treated with Adalimumab at conception/ 1st trimester [anti-TNFa therapy was discontinued between 7th-11th weeks of gestations (WG)]. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnancies in women withdrawn anti-TNFa prior to conception [anti-TNFa therapy was discontinued between one to six months prior to conception, following the leaflet recommendations].	5 / 11	Primary analyse concerned AntiTNFa group, which was further categorized into those exposed to ETN (n=17), ADA (n=5) or CZP (n=2) at conception; and 3 paternal exposures (ETN). Raw individual data provided for each substance and used for the meta-analysis.
Hyrich, 2006	United Kingdom Until 2005	Patients with rheumatic diseases directly exposed to anti-TNFa therapies during or immediately prior to pregnancy.	Patients who were directly exposed to adalimumab at the time of conception. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Patients who electively discontinued their anti-TNFa therapy prior to conceiving (range 1–10 months before conception).	3 / 9	All but 2 etanercept patients discontinued their during the first trimester of pregnancy.
Langen, 2014	USA 2001 - 2009	All pregnancies complicated by Rheumatoid arthritis (RA) delivered at the institution.	Women with adalimumab only 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).	1 / 15	Co-exposure Prednisolone, plaquenil and etanercept (discontinuation of Plaquenil and etanercept).
Schnitzler (Unexposed control, disease free), 2011	Belgium 1994 - 2007	Pregnant women who delivered at the University Hospital in Leuven.	Pregnant IBD patients treated with ADA within 3 months prior to conception and/or during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Matched pregnancies of healthy women out of the Flemish population who delivered at the University Hospital in Leuven.	7 / 56	Main analysis: pregnancies with IFX (n=35) or ADA (n =7), but for malformations, raw data provided for each substance and used for this meta-analysis.
Schnitzler (Unexposed control, sick), 2011	Belgium 1994 - 2007	Pregnant women who delivered at the University Hospital in Leuven.	Pregnant IBD patients treated with ADA within 3 months prior to conception and/or during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnancies after diagnosis of IBC but prior to start ADA treatment.	7 / 78	Main analysis: pregnancies with IFX (n=35) or ADA (n =7), but for malformations, raw data provided for each substance and used for this meta-analysis.
Seirafi, 2014	France and Belgium 2009 - 2010	Pregnant IBD patients	Pregnant IBD patients under Adalimumab within 3 months prior to conception and/or during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant IBD patients not treated with anti-TNF therapy.	42 / 99	Design seems to be a retrospective cohort rather than a case–control study as mentioned by authors. Exposures: IFX (n=86), ADA (n=42) or CTZ (n=5). Anti-TNFs were preventively discontinued before GW 30 in 73% of patients having completed their 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 Adalumimab from 3 months prior to pregnancy to delivery. (This is a 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.	3 / 1458	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 Adalumimab from 3 months prior to pregnancy to delivery. (This is a 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.	3 / 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.
Vinet (Unexposed controls, disease free), 2018	USA 2011 - 2015	The Pregnancies in RA Mothers and matched control group of children born to unaffected mothers.	Children born of rheumatoid arthritis (RA) women with ≥1 filled prescription of Adalimumab during the preconception and/or gestational periods. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Children born to non-RA mothers without TNFi exposure (i.e., no prescription filled or infusion procedure claim within the preconception and gestational periods).	108 / 14596	Primary analysis performed on the group of TNFi, but raw data related to serious infections provided by type of TNFi and used in this meta-analysis.
Vinet (Unexposed controls, sick), 2018	USA 2011 - 2015	The Pregnancies in RA Mothers and matched control group of children born to unaffected mothers.	Children born of rheumatoid arthritis (RA) women with ≥1 filled prescription of Adalimumab during the preconception and/or gestational periods. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Children born of rheumatoid arthritis (RA) women without TNFi exposure (i.e., no prescription filled or infusion procedure claim within the gestational period and the 12 weeks preceding it).	108 / 2476	Primary analysis performed on the group of TNFi, but raw data related to serious infections provided by type of TNFi and used in this meta-analysis.
Weber-Schoendorfer, 2015	Australia, Finland, France, Italy, The Netherlands, Turkey, Switzerland and the United Kingdom 1998 - 2013	Pregnant women who contact a Teratology information services (TIS), directly or via her health care professional.	Pregnant women who had been exposed to more than one dose of ADA at any time during the first 12 weeks after the last menstrual period (LMP). (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Pregnant women identified through spontaneous TIS consultations for other conditions or exposures such as hairdyeing, urinary tract infection, asthma or depression	172 / 1532	Analyses were performed for the group of 5 TNF-α inhibitors (172 ADA, 7 CZP, 140 ETA, 3 GOL and 168 IFX). Raw data were provided for major malformations and used for the meta-analysis.

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk

Warning! There are no case-control studies available for this drug.

47 studies, not fulfilled eligibility criteria, were excluded. See excluded tab for the list of these studies and reason of exclusion.

master protocol