Ustekinumab as salvage therapy for a flare of chronic ulcerative colitis in pregnancy: A case report

Introduction: Acute severe ulcerative colitis presents a challenge of medical management during pregnancy. Typically, infliximab, cyclosporine and more recently JAK-inhibitors are used as rescue therapy for steroid-refractory severe colitis. We present a patient with a flare of chronic UC during pregnancy where ustekinumab was used as salvage therapy.

Case Report: A 30-year-old pregnant G1P0 woman was admitted to hospital at 25+4 weeks with bloody diarrhoea on a background of left-sided ulcerative colitis. She had been diagnosed at age 16 and was initially managed on mesalazine and azathioprine. She had her first episode of ASUC in 2019 when she failed to respond to cyclosporine and was subsequently salvaged with infliximab. She continued infliximab 8 weekly infusions for 18 months, before transitioning to infliximab fortnightly subcutaneous injections, which maintained her in clinical remission. At the time of conception, she was also in endoscopic and histologic remission. At 8 weeks gestation, she showed the first signs of relapse with blood in her stools. This progressed to a hospital admission at 13 weeks for moderate severity colitis. She responded to IV corticosteroids and her infliximab was dose escalated to 4 weekly 5mg/kg infusions. At 25+4 weeks, she was readmitted with > 10 episodes of bloody diarrhoea per day. Biochemistry showed albumin 27g/L, CRP 29.5, faecal calprotectin 8020 ug/g and supratherapeutic infliximab trough levels (20.90 ug/mL). Flexible sigmoidoscopy demonstrated Mayo 3 colitis (UCEIS 7) to the descending colon. C.difficile and CMV infection were excluded. There was early MDT involvement comprising Gastroenterology, Colorectal Surgery, O&G and Neonatology. She received IV corticosteroids and was given off-label IV ustekinumab at an induction dose of 520mg on day 2. Her condition improved and she was transitioned to oral steroids a week later. She subsequently had worsening symptoms and was recommenced on IV corticosteroids. She tolerated a step down to oral steroids 2 weeks later and has remained stable on a weaning regimen since. She was discharged with an elective caesarean section planned for 34 weeks gestation. Non-invasive monitoring ensured foetal health throughout, and the latest ultrasound at 32 weeks has demonstrated a healthy 1.8kg foetus.

Conclusion: Ulcerative colitis flares during pregnancy presents a complex medical scenario and early MDT involvement is essential. This case was particularly difficult as traditional salvage medical therapies had been previously exhausted. Ustekinumab was able to avoid emergent colectomy and ultimately delay delivery to improve foetal outcomes.