Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes

Mette Julsgaard; Christian L Hvas; Richard B Gearry; Peter R Gibson; Jan Fallingborg; Miles P Sparrow; Bo M Bibby; William R Connell; Steven J Brown; Michael A Kamm; Ian C Lawrance; Thea Vestergaard; Lise Svenningsen; Mille Baekdal; Heidi Kammerlander; Alissa Walsh; Trine Boysen; Peter Bampton; Graham Radford-Smith; Jens Kjeldsen; Jane M Andrews; Kavitha Subramaniam; Gregory T Moore; Nanna M Jensen; Susan J Connor; Signe Wildt; Benedicte Wilson; Kathrine Ellard; Lisbet A Christensen; Sally J Bell

doi:10.1093/ibd/izz110

Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes

Inflamm Bowel Dis. 2020 Jan 1;26(1):93-102. doi: 10.1093/ibd/izz110.

Authors

Mette Julsgaard^{1

2

3}, Christian L Hvas¹, Richard B Gearry⁴, Peter R Gibson⁵, Jan Fallingborg⁶, Miles P Sparrow⁵, Bo M Bibby⁷, William R Connell³, Steven J Brown³, Michael A Kamm³, Ian C Lawrance^{8

9}, Thea Vestergaard¹, Lise Svenningsen^{2

10}, Mille Baekdal¹¹, Heidi Kammerlander^{12

13}, Alissa Walsh¹⁴, Trine Boysen¹⁵, Peter Bampton¹⁶, Graham Radford-Smith¹⁷, Jens Kjeldsen¹³, Jane M Andrews¹⁸, Kavitha Subramaniam¹⁹, Gregory T Moore²⁰, Nanna M Jensen²¹, Susan J Connor²², Signe Wildt²³, Benedicte Wilson²⁴, Kathrine Ellard²⁵, Lisbet A Christensen^{1

26}, Sally J Bell^{3

20}

Affiliations

¹ Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
² Department of Medicine, Horsens Hospital, Horsens, Denmark.
³ Department of Gastroenterology, St Vincent's Hospital, and University of Melbourne, Melbourne, Australia.
⁴ Department of Medicine, Christchurch Hospital, University of Otago, Christchurch, New Zealand.
⁵ Department of Gastroenterology, Alfred Hospital, and Monash University, Melbourne, VIC, Australia.
⁶ Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
⁷ Department of Biostatistics, University of Aarhus, Aarhus, Denmark.
⁸ School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute for Medical Research, Murdoch, WA, Australia.
⁹ Centre for inflammatory Bowel Diseases, Saint John of God Hospital, Subiaco, WA, Australia.
¹⁰ Department of Medicine, Herning Hospital, Herning, Denmark.
¹¹ Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
¹² Department of Gastroenterology, Hospital of Southwest Jutland, Esbjerg, Denmark.
¹³ Department of Gastroenterology, Odense University Hospital, Odense, Denmark.
¹⁴ Department of Gastroenterology, St. Vincent's Hospital, Sydney, NSW, Australia.
¹⁵ Gastrounit, Medical Division, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
¹⁶ Department of Gastroenterology, Flinders Medical Centre, Bedford Park, SA, Australia.
¹⁷ Inflammatory Bowel Diseases Unit, Royal Brisbane & Women's Hospital, University of Queensland School of Medicine, Brisbane, QLD, Australia.
¹⁸ Department of Gastroenterology & Hepatology, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia.
¹⁹ Gastroenterology and Hepatology Unit, The Canberra Hospital, Australian National University, Canberra, ACT, Australia.
²⁰ Department of Gastroenterology, Monash Health, and School of Clinical Sciences Monash University, Melbourne, VIC, Australia.
²¹ Abdominalcenter K, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
²² Department of Gastroenterology, Liverpool Hospital, Sydney, University of NSW, and Ingham Institute of Applied Medical Research, Sydney, Australia.
²³ Medical Department, Zealand University Hospital, Køge, Denmark.
²⁴ Department of Internal Medicine, Nykøbing Falster Hospital, Nykøbing, Denmark.
²⁵ Mater Hospital, Department of Gastroenterology, Sydney, Australia.
²⁶ Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.

PMID: 31141607
DOI: 10.1093/ibd/izz110

Abstract

Background: Active inflammatory bowel disease (IBD) adversely affects pregnancy outcomes. Little is known about the risk of relapse after stopping anti-tumor necrosis factor (anti-TNF) treatment during pregnancy. We assessed the risk of relapse before delivery in women who discontinued anti-TNF treatment before gestational week (GW) 30, predictors of reduced infant birth weight, a marker associated with long-term adverse outcomes, and rates and satisfaction with counseling.

Methods: Pregnant women with IBD receiving anti-TNF treatment were prospectively invited to participate in an electronic questionnaire carried out in 22 hospitals in Denmark, Australia, and New Zealand from 2011 to 2015. Risk estimates were calculated, and birth weight was investigated using t tests and linear regression.

Results: Of 175 women invited, 153 (87%) responded. In women in remission, the relapse rate did not differ significantly between those who discontinued anti-TNF before GW 30 (1/46, 2%) compared with those who continued treatment (8/74, 11%; relative risk, 0.20; 95% confidence interval [CI], 0.02 to 1.56; P = 0.08). Relapse (P = 0.001) and continuation of anti-TNF therapy after GW 30 (P = 0.007) were independently associated with reduced mean birth weight by 367 g (95% CI, 145 to 589 g; relapse) and 274 g (95% CI, 77 to 471 g; anti-TNF exposure after GW 30). Of 134 (88%) women who received counseling, 116 (87%) were satisfied with the information provided.

Conclusions: To minimize fetal exposure in women in remission, discontinuation of anti-TNF before GW 30 seems safe. Relapse and continuation of anti-TNF therapy after GW 30 were each independently associated with lower birth weight, although without an increased risk for birth weight <2500 g. Most women received and were satisfied with counseling.

Keywords: anti–tumor necrosis factor alpha; counseling; inflammatory bowel disease; pregnancy; pregnancy outcome.

Publication types

Evaluation Study
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Australia
Denmark
Female
Humans
Infant, Low Birth Weight
Infant, Newborn
Inflammatory Bowel Diseases / drug therapy*
Linear Models
Maternal Exposure / adverse effects
Maternal Exposure / prevention & control
New Zealand
Patient Acceptance of Health Care
Pregnancy
Pregnancy Complications / drug therapy*
Pregnancy Outcome
Pregnancy Trimester, Third / drug effects
Prospective Studies
Recurrence
Treatment Outcome
Tumor Necrosis Factor Inhibitors / therapeutic use*
Withholding Treatment

Substances

Tumor Necrosis Factor Inhibitors