Intentional infliximab use during pregnancy for severe steroid-refractory ulcerative colitis

Dear Sir,

The use of biologics during pregnancy is a cause of great concern for patients and physicians even though, to date, there is no evidence that anti-TNFα are associated with adverse pregnancy outcomes.¹ Most reports of infliximab use in Inflammatory Bowel Disease (IBD) during pregnancy address inadvertent exposure and only few series of intentional use have been published.²,³ We describe the case of a pregnant woman with severe steroid-refractory ulcerative colitis (UC), who intentionally received infliximab as rescue therapy and could avoid colectomy.

A 36-year-old woman in the 12th gestational week was admitted to our GI Unit for a severe attack of UC. She was diagnosed with pancolitis several years before but, in the last years, the disease was in remission and the patient showed poor compliance to maintenance therapy. At admission, she presented more than 10 bowel movements per day, constant rectal bleeding and abdominal pain. Laboratory studies showed increased C-reactive protein (CRP) (12.2 mg/dl; normal range < 0.8 mg/dl), anaemia (haemoglobin 10.6 g/dl), and hypoalbuminemia (2.3 g/dl). No pathogens, ova, parasites or Clostridium difficile toxin A and B could be detected in stools. Sigmoidoscopy showed erythema, friability, erosions and superficial ulcerations. Histologic examination was consistent with UC: no cytomegalovirus inclusions were observed. Obstetric ultrasound indicated a viable and normally developing foetus.

Intravenous 6-methyl-prednisolone 60 mg/day was administered. A partial clinical response occurred within 5 days but, despite a reduction of diarrhoea and rectal bleeding, bowel movements were 6 per day and CRP values were 9.2 mg/dl. Intravenous steroids were administered further for 3 days but no improvement occurred. At the 14th gestational week infliximab 5 mg/kg was administered. The patient entered remission within 5 days: steroid dose was tapered and infliximab was administered at week 2 and 6 (20th gestational week). Maintenance infliximab was not considered because we avoided administration during the third trimester of pregnancy when the drug crosses the placenta. Maintenance treatment with oral and topical mesalazine was administered and the course of pregnancy in the following weeks was uneventful.

At the 33th gestational week ultrasound showed a growth retardation of the foetus and at the 37th week foetal heart rate monitor revealed a decrease in the heart rate indicating distress. The option was to terminate the pregnancy by caesarean section. There were no peripartum complications or neonatal morbidities with the newborn weighing 2.450 g (small for gestational age). After 4 weeks of breast feeding, the newborn's weight increased to 3.350 g which is considered normal for age.

The presented case confirms that during pregnancy, in appropriate clinical setting, the benefits of infliximab outweigh the risks. Although severe UC during pregnancy is uncommon, it is a worrisome obstetrical factor and an aggressive management is critical to optimise both maternal and foetal health. Avoiding colectomy is particularly relevant. Although recent data indicate that colectomy for severe UC during pregnancy could be safe, previous reports suggested an increased risk of foetal death and maternal morbidity.⁴ Therefore, although pregnancy is not an absolute contraindication for surgical procedures, surgery should be delayed if possible.⁵