What is the next best step in managing a 15-year-old female with ASUC on day 3 of IV steroids, with persistent symptoms and elevated CRP?

Management of Acute Severe Ulcerative Colitis on Day 3 of IV Steroids

For this 15-year-old female with ASUC who is on day 3 of IV steroids with persistent symptoms (4 stools/day with rectal bleeding) and elevated CRP (17 mg/L), rescue therapy with intravenous infliximab should be initiated immediately as she is showing signs of steroid refractoriness. 1

Assessment of Current Status

The patient shows signs of steroid refractoriness based on:

• Day 3 of IV steroids with persistent symptoms
• Stool frequency of 4 per day with rectal bleeding
• CRP of 17 mg/L
• Previous treatment experience with steroids, 5-ASA, and tofacitinib

According to the British Society of Gastroenterology guidelines, patients with ASUC not responding to at least 3 days of IV corticosteroids should be treated with rescue therapy 1.

Management Algorithm

Step 1: Determine Steroid Response

Several indices can predict failure of corticosteroid therapy:

• Stool frequency >3 per day on day 3 (patient has 4)
• CRP >45 mg/L (patient has 17 mg/L)
• CRP/albumin ratio >0.85 (need albumin value to calculate) 1, 2

Step 2: Initiate Rescue Therapy

• First-line rescue option: Intravenous infliximab

  • Standard dosing: 5 mg/kg at weeks 0,2, and 6, then every 8 weeks
  • Consider accelerated/intensified dosing regimen, especially if albumin is low 1
  • Monitor serum infliximab levels if available 3

• Alternative rescue option: Intravenous ciclosporin

  • Initial dose: 2 mg/kg/day IV with target trough concentration of 150-250 ng/mL
  • Can be bridged to purine analogues if naive 1

Step 3: Surgical Consultation

• Early referral to colorectal surgery is essential as delay in surgery is associated with increased surgical complications 1, 4
• Surgical team should be involved in the care plan immediately

Step 4: Close Monitoring

• Daily assessment of clinical status, stool frequency, and rectal bleeding
• Regular monitoring of CRP, albumin, and other laboratory parameters
• Consider flexible sigmoidoscopy if not already performed

Important Considerations

Timing of Decision-Making

• Do not delay rescue therapy beyond day 3 if steroid response is inadequate
• Early intervention with rescue therapy improves outcomes 1, 4
• If no response to rescue therapy within 7 days, colectomy should be considered 1

Special Considerations for Pediatric Patients

• This 15-year-old has already experienced tofacitinib, which is unusual in pediatric IBD
• A retrospective cohort study showed that in pediatric patients with ASUC for whom corticosteroids and infliximab had failed, tofacitinib resulted in 73% being free of colectomy at 90 days 1

JAK Inhibitor Considerations

• While the patient has experience with tofacitinib, its use in ASUC should be approached with caution due to thrombosis risk 1
• Upadacitinib may be considered as a salvage option if infliximab fails, though evidence is limited 5

Cautions and Pitfalls

1. Avoid delaying rescue therapy: Delay beyond day 3 is associated with worse outcomes and higher complication rates 4

2. Do not overlook infections: Ensure stool cultures and C. difficile testing have been performed, but do not delay treatment while awaiting results 1

3. Beware of thrombosis risk: JAK inhibitors carry increased risk of thrombotic events, especially in ASUC which is itself a risk factor for thrombosis 1

4. Monitor nutritional status: Ensure adequate protein intake (1.2-1.5 g/kg/day) and caloric intake (30-35 kcal/kg/day) to offset catabolism from corticosteroids 6

5. Don't delay surgical consultation: Early involvement of surgical team is essential for optimal outcomes 1, 4

The decision between infliximab and ciclosporin should be based on the patient's previous medication history. Given her prior exposure to tofacitinib, infliximab would be the preferred rescue therapy option in this case.