Most IBD medications are safe for use while trying to conceive and to continue during pregnancy but certain medications may need to be adjusted. Please read below for a summary of IBD medications.

Aminosalicylates: Most formulations of 5-ASA are considered safe to continue into pregnancy1,2  Studies have found no significant association between 5-ASA drugs and poor pregnancy outcomes3. The coating of one 5-ASA medication (Asacol ©) contains dibutyl phthalate (DBP) which has been associated with abnormal development in animal models. However, there has been no significant findings among humans1,3,4.

Sulfasalazine (Salazopyrin©) is considered safe to use before and during pregnancy5 However, since sulfasalazine inhibits folate synthesis, women taking this medication should also be taking folic acid supplements1,5.  Men taking sulfasalazine should be switched to another oral mesalamine because sulfasalazine has been associated with oligospermia (low sperm concentration)5. 

Thiopurines: Azathioprine (Imuran©) and 6-mercaptopurine (6-MP) (Purinethol©) can be continued during preconception and during pregnancy if needed for maintenance therapy. Although studies have reported abnormalities in animal models, and older studies reported some risk of adverse outcomes among pregnant women taking these medications, recent larger studies on women with IBD taking thiopurines suggest no significant adverse outcomes6-8.

Corticosteroids: Steroids, such as budesonide (Entocort©) and prednisone (Deltasone©) can be used to treat active IBD before and during pregnancy9. However, there is a small risk of cleft palate in neonates exposed to corticosteroids in the first trimester10,11.

Biologics (anti-TNF): Adalimumab (Humira® and biosimilars), infliximab (Remicade® and biosimilars), and Golimumab (Simponi®) are considered safe to continue into pregnancy.   However, studies have shown that these proteins cross the placenta to the neonate after 22 weeks of gestation. Therefore, physicians often administer the last dose of biologics before the third trimester, to minimize fetal exposure to the medication. However, women with IBD who require biologic anti-TNF therapy during pregnancy may continue the medications if the risks of having uncontrolled IBD outweigh the risks of fetal exposure1,3,9,10,11,12,14.

Biologics (anti-alpha4/beta7 integrin): Vedolizumab (Entyvio®) is considered safe to continue into pregnancy, although has the least data in use in pregnancy as it is the first IBD gut specific drug on the market13-17. To minimize exposure to the fetus, timing of the dosing is approached in similar fashion as the anti-TNF agents.

Biologics (anti-IL12/23 p40): Ustekinumab (Stelara®) is considered safe to continue into pregnancy, based on the limited available information from clinical trials observations, and clinical cohorts15-20.  There are longer term safety data from the psoriasis PSOLAR registry, and now some IBD-specific cohort studies from France, Czech, and Israel.  To minimize exposure to the fetus, timing of the dosing is approached in similar fashion as the anti-TNF agents.

Biologics (anti-IL23 p19): Risankizumab (Skyrizi®) and Mirikizumab (Omvoh®) are considered safe to continue into pregnancy (although there is very limited data available from clinical trials observations, they are a similar type of protein molecule as the other biologics).

Methotrexate (Rheumatrex®) is contraindicated to use in women who are trying to become and during pregnancy1,3.  Methotrexate can cause malformation of an embryo) and can cause fetal death.10 Furthermore, because it can remain in the body for an extended time period, physicians recommend that both men and women with IBD who are on Methotrexate discontinue use for 3 to 6 months prior to trying to conceive11

Small Molecule (JAK inhibitor): Tofactinib (Xeljanz®) and Upadacitinib (Rinvoq®) are contraindicated for use preconception and in pregnancy due to teratogenic effects noted in animal pre-clinical studies, and limited evidence of safety in use in humans19.

Small Molecule (S1P modulator): Ozanimod (Zeposia®) is contraindicated for use preconception and in pregnancy due to teratogenic effects in animal pre-clinical studies, and limited evidence of safety in use in humans.

References

  1. Biedermann L et al. Pregnancy and Breastfeeding in Inflammatory Bowel Disease. Digestion. 2012;86:45-54.
  2. Rahimi R et al. Pregnancy outcomes in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: A meta-analysis. Reproductive Toxicology. 2008;25:271-275.
  3. Ng S W &Mahadevan U. Management of inflammatory bowel disease in pregnancy. Expert Rev ClinImmunol. 2013;9(2):161-174.
  4. Asacol (mesalamine), package insert. Warner Chilcott Pharmaceuticals Inc. OH, USA (2010).
  5. Riley S A et al. Sulphasalazine induced seminal abnormalities in ulcerative colitis: results of mesalazine substitution. Gut. 1987 Aug;28(8):1008-12
  6. Shim L et al. The effects of azathioprine on birth outcomes in women with inflammatory bowel disease (IBD). J Crohns Colitis. 2011;5:234-238.
  7. Saha S & Wald A. Safety and efficacy of immunomodulators and biologics during pregnancy and lactation for the treatment of inflammatory bowel disease. Expert Opin. Drug Saf. 2012;11(6):947-957.
  8. Casanova M J et al. Safety of thiopurines and anti-TNFα drugs during pregnancy in patients with inflammatory bowel disease. Am J Gastroenterol. 2013;108:433-440.
  9. Huang V W & Habal F M. From conception to delivery: Managing the pregnant inflammatory bowel disease patient. World J Gastroenterol. 2014;20(13).
  10. Neilsen O H, Maxwell C, & Hendel J. IBD medications during pregnancy and lactation. Nat Rev Gastroenterol Hepatol. 2014;11:116-127.
  11. Van der Woude C J et al.  European evidence-based consensus on reproduction in inflammatory bowel disease. J Crohns Colitis. 2010;4:493-510.
  12. Huang V W & Habal F M. From conception to delivery: Managing the pregnant inflammatory bowel disease patient. World J Gastroenterol. 2014;20(13).
  13. Mahadevan U, Vermeire S, Lasch K, et al.  Vedolizumab exposure in pregnancy: outcomes from clinical studies in inflammatory bowel disease.  Aliment Pharmacol Ther 2017;45:941-950.
  14. Moens A, van der Woude CJ, Julsgaard M, et al. Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study. Aliment Pharmacol Ther 2020; 51:129–138.
  15. Wils P, Seksik P, Stefanescu C, et al. Safety of ustekinumab or vedolizumab in pregnant inflammatory bowel disease patients: a multicentre cohort study. Aliment Pharmacol Ther. 2021 Feb; 53 (4): 460-70.
  16. Mitrova K, Pipek B, Bortlik M et al. Safety of ustekinumab and vedolizumab during pregnancy – pregnancy neonatal and infant outcome: a prospective multicentre study. J Crohns Colitis 2022.
  17. Chugh R, Long M, Jiang Y, et al. Maternal and Neonatal Outcomes in Vedolizumab and Ustekinumab Exposed Pregnancies: Results from the PIANO registry. Am J Gastroenterol 2023 Oct 5.
  18. Avni-Biron I, Mishael T, Zittan E, et al. Ustekinumab during pregnancy in patients with inflammatory bowel disease: a prospective multicentre cohort study. Aliment Pharmacol Ther. 2022;56(9):1361-1369.
  19. Mahadevan U, Naureckas S, Tikhonov I et al. Pregnancy outcomes following periconceptional or gestational exposure to ustekinumab: Review of cases reported to the manufacturer’s global safety database. Aliment Pharmacol Ther 2022;56(3):477-490.
  20. Scherl E, Jacobstein D, Murphy C, et al.  A109: Pregnancy Outcomes in Women Exposed to Ustekinumab in the Crohn’s Disease Clinical Development Program.  JCAG 2018;1(2): 166. https://doi.org/10.1093/jcag/gwy009.109
  21. Mahadevan U, Dubinsky MC, Su C, et al. Outcomes of Pregnancies With Maternal/Paternal Exposure in the Tofacitinib safety Databases for Ulcerative Colitis. Inflamm Bowel Dis 2018;24(12):2494-2500.
  22. Nielsen OH GJ, Juhl CB, Streett SE, Maxwell C. Biologics for Inflammatory Bowel Disease and their Safety in Pregnancy: A Systematic Review and Meta-analysis. Clin Gastroenterology Hepatol 2020.
  23. Gubatan, J, Nielsen, OH, Levitte, S, et al. Biologics during pregnancy in women with inflammatory bowel disease and risk of infantile infections: a systematic review and meta-analysis. Am J Gastroenterol 2021; 116: 243–253

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Preg.IBD@sinaihealth.ca