Adalimumab

Exposed non-exposed, cohort studies

Study Country
Study period
Study design
Data source Exposure definition Non-exposure definition Exposition period Sample size
(exposed/unexposed) Or (case / control)
Remarks Risk of bias
Broms (Controls exposed to other treatments)
2020
Denmark, Finland and Sweden
2006 - 2013
population based cohort retrospective
A population-based study based on nationwide medical birth registers, patient registers, and registers of prescribed drugs, 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.
3 months (or more) before pregnancy or during pregnancy 257 / 9393
The national prescribed drug registers. Information was also identified from the National Patient Register (Denmark), from the register for biologic treatment (Finland) and from the ARTIS and PsoReg registers (Sweden).
Bröms (controls unexposed, disease free)
2016
Denmark and Sweden
2004/6 - 2012
population based cohort retrospective
National danish and swedish population-based health registers: the national medical birth registers, patient registers, and registers on prescribed drugs 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).
3 months or more before pregnancy or1st trimester 161 / 1250192 Primary analyse on Anti-TNF, with individual result by substance (n=161 ADA).
The national registers on prescribed drugs. Anti-TNF treatment also identified from visits recorded in the patient register covering all Danish hospitals using a specific treatment code (Denmark) or from the ARTIS and PsoReg registers (Sweden).
Broms (Controls unexposed, disease free)
2020
Denmark, Finland and Sweden
2006 - 2013
population based cohort retrospective
A population-based study based on nationwide medical birth registers, patient registers, and registers of prescribed drugs, 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).
3 months (or more) before pregnancy or during pregnancy 257 / 1623483
The national prescribed drug registers. Information was also identified from the National Patient Register (Denmark), from the register for biologic treatment (Finland) and from the ARTIS and PsoReg registers (Sweden).
Bröms (controls unexposed, sick)
2016
Denmark and Sweden
2004/6 - 2012
population based cohort retrospective
National danish and swedish population-based health registers: the national medical birth registers, patient registers, and registers on prescribed drugs 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.
3 months or more before pregnancy or1st trimester 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%).
The national registers on prescribed drugs. Anti-TNF treatment also identified from visits recorded in the patient register covering all Danish hospitals using a specific treatment code (Denmark) or from the ARTIS and PsoReg registers (Sweden).
Casanova
2013
Spain
Not specified
retrospective cohort
Inflammatory bowel disease (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).
3 months (or more) before pregnancy or during pregnancy 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.
Data were obtained from the review of medical records and an interview with the patient when additional information was necessary was conducted. Collected data including data on drugs received during 3 months before conception and during pregnancy.
Chambers (Controls unexposed, disease free)
2019
USA and Canada
2004 - 2016
prospective cohort
The MotherToBaby pregnancy study conducted by the Organization of Teratology Information Specialists (OTIS). 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.
at least 1st trimester 257 / 225
Pregnant women completed up to three telephone interviews during pregnancy, including data on on all medications (prescription, over-the-counter) used/administered during pregnancy.
Chambers (Controls, sick)
2019
USA and Canada
2004 - 2016
prospective cohort
The MotherToBaby pregnancy study conducted by the Organization of Teratology Information Specialists (OTIS). 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.
at least 1st trimester 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).
Pregnant women completed up to three telephone interviews during pregnancy, including data on on all medications (prescription, over-the-counter) used/administered during pregnancy.
De Lorenzo (Controls unexposed, disease free)
2020
Italy
2009 - 2017
retrospective cohort
The Clinic for Pregnancy and Autoimmunity at the San Raffaele University Hospital, Milan, Italy. 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.
at least 1st trimester 2 / 36
Data were collected retrospectively during paediatric consultations.
De Lorenzo (Controls unexposed, sick)
2020
Italy
2009 - 2017
retrospective cohort
The Clinic for Pregnancy and Autoimmunity at the San Raffaele University Hospital, Milan, Italy. 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).
at least 1st trimester 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.
Data were collected retrospectively during paediatric consultations.
Hoxha
2017
Italia
2008 - 2015
prospective cohort
Four Rheumatology Units (Belluno, Padua, Trento and Udine) 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].
1st trimester 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.
A form including information on biological agents exposure, the concomitant use of disease modifying antirheumatic drugs was filled out by the treating rheumatologist.
Hyrich
2006
United Kingdom
Until 2005
retrospective cohort
The British Society for Rheumatology Biologics Register (BSRBR) 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).
1st trimester 3 / 9 All but 2 etanercept patients discontinued their during the first trimester of pregnancy.
The British Society for Rheumatology Biologics Register (BSRBR) database was searched for all reports of pregnancy. Details on exposure to disease-modifying antirheumatic drugs (DMARDs) and biologic drugs were collected using standardized forms.
Langen
2014
USA
2001 - 2009
retrospective cohort
Perinatal database of a tertiary care referral hospital. 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).
at least 1st trimester 1 / 15 Co-exposure Prednisolone, plaquenil and etanercept (discontinuation of Plaquenil and etanercept).
Data were collected from review of medical records and included medication use.
Schnitzler (Unexposed control, disease free)
2011
Belgium
1994 - 2007
prospective cohort
Cohort 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.
3 months (or more) before pregnancy or during pregnancy 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.
Patients were treated with IFX or with ADA in our IBD unit at the University Hospital in Leuven and were prospectively followed.
Schnitzler (Unexposed control, sick)
2011
Belgium
1994 - 2007
prospective cohort
Cohort 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.
3 months (or more) before pregnancy or during pregnancy 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.
Patients were treated with IFX or with ADA in our IBD unit at the University Hospital in Leuven and were prospectively followed.
Seirafi
2014
France and Belgium
2009 - 2010
retrospective cohort
GETAID (Groupe d’Etude Thérapeutique des Affections du Tube Digestif) centres and CESAME registry 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.
3 months (or more) before pregnancy or during pregnancy 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.
Inclusion: patient records from hospital IBD units and patients were contacted by phone when data were missing. During pregnancy, information collected included dose and duration of anti-TNFs and concomitant treatments.
Viktil (Controls exposed to other treatments)
2012
Norway
2004 - 2007
population based cohort propective
Two nationwide health registers, the Norwegian Prescription Database (NorPD) and the Medical Birth Registry of Norway (MBRN) 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 months or more before pregnancy or1st trimester 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.
Prescriptions were recorded from 3 months prior to conception until labour from the Norwegian Prescription Database (NorPD).
Viktil (Controls unexposed, NOS)
2012
Norway
2004 - 2007
population based cohort propective
Two nationwide health registers, the Norwegian Prescription Database (NorPD) and the Medical Birth Registry of Norway (MBRN) 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 months or more before pregnancy or1st trimester 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.
Prescriptions were recorded from 3 months prior to conception until labour from the Norwegian Prescription Database (NorPD).
Vinet (Unexposed controls, disease free)
2018
USA
2011 - 2015
retrospective cohort (claims database)
The RA Mothers and Outcomes in Offspring in the United States (PAROUS) cohort and the MarketScan commercial databases. 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).
during pregnancy (anytime or not specified) 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.
The MarketScan commercial database is a large prospective US database of >230 million subjects containing drug prescription claims.
Vinet (Unexposed controls, sick)
2018
USA
2011 - 2015
retrospective cohort (claims database)
The RA Mothers and Outcomes in Offspring in the United States (PAROUS) cohort and the MarketScan commercial databases. 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).
during pregnancy (anytime or not specified) 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.
The MarketScan commercial database, a large prospective US database of >230 million subjects, containing drug prescription claims.
Weber-Schoendorfer
2015
Australia, Finland, France, Italy, The Netherlands, Turkey, Switzerland and the United Kingdom
1998 - 2013
prospective cohort
European Network of Teratology information services (TIS) 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
1st trimester 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.
Data on exposure (including both prescription and over-the-counter) were collected from structured telephone or face-to-face interviews and/or mailed questionnaires obtained from both the mother and/or her physician(s) after oral informed consent.

Case-control studies

Study Country
Study period
Study design
Data source Case Control Exposition Exposition period Sample size
(exposed/unexposed) Or (case / control)
Remarks Risk of bias

Risk of bias: : NA;   : low;   : moderate;   : serious;   : critical;   : unclear;  

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

master protocol