To the Editor:

We read with interest the article by Korelitz et al1 concerning the use of immunomodulators and biological medications in pregnant women with inflammatory bowel diseases. Persistently high activity in women affected by Crohn's disease (CD) seems to be associated with a poorer pregnancy outcome with respect to healthy women.2 Tumor necrosis factor alpha (TNF alpha) antagonists have been demonstrated to be effective in inducing and maintaining remission in CD.3, 4 To date, there is no evidence coming from toxicity studies that TNF alpha antagonists are associated with embriotoxicity or teratogenicity.5 Experience in pregnant women exposed to TNF alpha antagonists is still limited. However, according to FDA classification, infliximab, a chimeric monoclonal antibody antiTNF alpha, is considered a pregnancy category B drug (“no documented human toxicity”).

We report the case of a woman who inadvertently received infliximab for the treatment of fistulizing CD within 3 months of conception.

A 31-year-old woman with colonic CD was referred to our Gastroenterology Unit in July 2004 on account of an anovaginal fistula draining mucopurulent material. CD had been diagnosed in May 2002 according to standard endoscopic, radiologic, and histologic criteria. In July 2002, for the development of an anovaginal fistula (2.5 cm from the anal verge), treatment with antibiotic (ciprofloxacin 1 g/day and metronidazole 750 mg/day) and immunosuppressive (azathioprine 2 mg/kg per day) drugs was started with partial closure of the fistula. In July 2004, for the reopening of the fistula and for a moderate relapse of intestinal symptoms (Crohn's Disease Activity Index [CDAI] 260), she received infliximab infusions (5 mg/kg) at weeks 0 and 2. Each infusion was preceded by premedication with hydrocortisone 100 mg iv.

Three weeks after the second infliximab infusion, the patient was found to be pregnant in the 6th gestational week, and she decided to allow the pregnancy even though she was informed about the absence at that time, of well-known data on the safety of infliximab in pregnancy as well as on fetal outcomes. At the same time the patient chose to stop infliximab and azathioprine therapies once pregnancy was known.

During the follow-up the patient was persistently symptom free throughout the pregnancy (CDAI < 150) under mesalazine maintenance treatment (2.4 g/day). In April 2005, in the 39th gestational week, the pregnancy ended in a live healthy birth. Due to the presence of the anovaginal fistula and prior history, the patient underwent a caesarean section. Weight of the child at birth was 3200 kg. No congenital malformations, intrauterine growth retardation, or neonatal illnesses were reported. Breast feeding was allowed.

In August 2006 the patient presented a moderate relapse of the disease with diarrhea and drainage of mucopus from the anovaginal fistula (CDAI 220). Antibiotics (metronidazole 750 mg/day) and azathioprine (2 mg/kg per day) were started again with resolution of intestinal symptoms and partial closure of the fistula. In July 2007, after 3 years of follow-up from the last infliximab infusion, CD was in clinical remission, and both mother and child had no medical problems.

Our case report confirms data from the existing literature on the relative safety of inadvertent and/or intentional use of infliximab during pregnancy. According to FDA drug safety classification, infliximab is considered a pregnancy category B drug (“no documented human toxicity”). Multiple case reports, data from the Infliximab Safety Database, TREAT registry,6, 7 and rheumatological surveys8 had not shown poorer outcome for pregnant women exposed to infliximab with respect to the general population of pregnant women. A first series of 10 pregnant women treated intentionally with infliximab during pregnancy for active CD9 has shown a substantially similar outcome.

In conclusion, even if available data do not show an increased risk of illness both for mothers and children coming from inadvertent or intentional use of infliximab during pregnancy, caution should be taken in using biological medications in pregnant women, as human experience is still extremely limited. Use of infliximab during pregnancy should probably be limited to cases in which uncontrolled activity of intestinal disease could expose both mother and child to risks greater than those only potentially coming from the use of biologic therapies.


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  • 1
    Korelitz BI. Continuing immunomodulators and biologic medications in Pregnant IBD patients—sometimes con. Inflamm Bowel Dis. 2007; 13: 14411442.
  • 2
    Fonager K, Sorensen HT, Olsen J, et al. Pregnancy outcome for women with Crohn's disease: a follow-up study based on linkage between national registries. Am J Gastroenterol. 1998; 93: 24262430.
    Direct Link:
  • 3
    Targan SR, Hanauer SB, van Deventer SJ, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's disease cA2 Study Group. N Engl J Med. 1997; 337: 10291035.
  • 4
    Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002; 359: 15411549.
  • 5
    Treacy G. Using an analogous monoclonal antibody to evaluate the reproductive and chronic toxicity potential for a humanized anti-TNFα monoclonal antibody. Hum Exp Toxicol. 2000; 19: 226228.
  • 6
    Katz JA, Antoni C, Keenan GF, et al. Outcome of pregnancy in women receiving infliximab for the treatment of Crohn's disease and rheumatoid arthritis. Am J Gastroenterol. 2004; 99: 23852392.
    Direct Link:
  • 7
    Lichtenstein G, Feagan BG, Cohen RD, et al. Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. Clin Gastroenterol Hepatol. 2006; 4: 621630.
  • 8
    Roux CH, Brocq O, Breuil V, et al. Pregnancy in rheumatology patients exposed to anti-tumor necrosis factor (TNF)-alpha therapy. Rheumatology (Oxford). 2007; 46: 695698.
  • 9
    Mahadevan U, Kane S, Sandborn WJ, et al. Intentional infliximab use during pregnancy for induction or maintenance of remission in Crohn's disease. Aliment Pharmacol Ther. 2005; 21: 733738.

Erika Angelucci MD*, Andrea Cocco MD*, Angelo Viscido MD, PhD*, Renzo Caprilli MD*, * Department of Clinical Sciences, Gastroenterology Unit, University of Rome “La Sapienza” Rome, Italy.