Rescue therapy for IVCS nonresponders
›Infliximab IV
›First-line rescue in most ASUC settings
›5 mg/kg IV as single infusion
›Consider accelerated dosing in very sick patients: repeat dose at week 1 or 2
›Efficacy data
›Approximately 65-70% of IVCS nonresponders respond to infliximab or cyclosporine
›Colectomy-free survival at 3 months approximately 65-80%
›Contraindications
›Active sepsis or serious infection
›Active TB or fungal infection
›Hepatitis B reactivation risk: test before use
›Post-rescue monitoring
›Infusion reaction monitoring
›Transition to maintenance infliximab
›Cyclosporine IV
›2 mg/kg/day as continuous IV infusion
›Target serum trough level 250-400 ng/ml
›Duration: 3-7 days then oral transition
›Oral transition
›Oral cyclosporine 5-8 mg/kg/day divided twice daily
›Bridge to thiopurine maintenance
›Monitoring
›Daily creatinine, electrolytes, blood pressure
›Nephrotoxicity and seizure risk
›Avoid in renal insufficiency or uncontrolled hypertension
›Tofacitinib as salvage option
›Observational data in anti-TNF-exposed ASUC
›90-day colectomy-free survival approximately 86%
›Off-label use in acute severe setting
›Dosing
›10 mg PO TID for up to 16 weeks induction
›Rapid oral bioavailability: onset within days
›Risk considerations
›VTE risk: not ideal when VTE prophylaxis challenging
›FDA black box: thrombosis, malignancy, serious infection
›Cardiovascular risk assessment required
Mild to moderate flare treatment
›Step 1: Optimize 5-ASA therapy
›Oral mesalamine
›>= 2 g/day, up to 4.8 g/day
›Divided dosing vs once daily: once daily equivalent efficacy
›Topical mesalamine adjunct
›Rectal suppository 1 g/day for proctitis
›Enema 1-4 g/day for left-sided disease
›5-ASA hypersensitivity
›Paradoxical worsening in some patients
›Stop if worsening occurs after initiation
›Step 2: Budesonide MMX if 5-ASA insufficient
›9 mg orally once daily for 8 weeks
›Minimal systemic absorption
›Lower HPA axis suppression than prednisone
›Appropriate for mild to moderate pancolitis or left-sided disease
›ACG 2025 recommendation
›Not adequate for ASUC
›Step 3: Systemic oral prednisone for inadequate budesonide response
›40-60 mg/day orally
›Taper: reduce by 10 mg/week to 20 mg then 5 mg/week
›Target taper complete within 2-3 months
›Steroid bridging
›Initiate steroid-sparing therapy simultaneously
›Do not stop steroids before advanced therapy takes effect
›Bone protection
›Calcium 1000-1200 mg/day and Vitamin D 800-1000 IU/day
›DEXA scan if cumulative steroid exposure significant
Advanced therapy: moderate to severe steroid-refractory disease
›Biologic agents (AGA 2024 Living Guideline)
›Anti-TNF agents
›Infliximab: 5 mg/kg IV at weeks 0, 2, 6 then every 8 weeks
›Adalimumab: 160 mg SC week 0, 80 mg week 2, then 40 mg every 2 weeks
›Golimumab: 200 mg SC week 0, 100 mg week 2, then 50-100 mg every 4 weeks
›Vedolizumab (gut-selective integrin inhibitor)
›300 mg IV at weeks 0, 2, 6 then every 8 weeks
›Favorable safety profile
›Slower onset compared to anti-TNF
›IL-23 inhibitors
›Risankizumab: 1200 mg IV induction at weeks 0, 4, 8 then 360 mg SC every 8 weeks
›Guselkumab: 200 mg SC every 4 weeks induction then 100 mg SC every 8 weeks
›Small molecules
›JAK inhibitors
›Tofacitinib: 10 mg PO twice daily for 8 weeks induction then 5-10 mg twice daily maintenance
›Upadacitinib: 45 mg PO once daily 8 weeks induction then 15-30 mg once daily maintenance
›FDA black box: malignancy, thrombosis, serious infection; cardiovascular risk assessment required
›S1P receptor modulators
›Ozanimod: 0.23 mg daily 1 week then 0.46 mg daily 1 week then 0.92 mg daily
›Etrasimod: 2 mg daily
›Cardiac monitoring required for first-dose bradycardia
›Colectomy indications
›Emergent
›Perforation
›Toxic megacolon unresponsive to 48-72 hours of medical therapy
›Massive haemorrhage not controlled by endoscopy
›Urgent (after failed medical therapy)
›Failed IVCS and rescue therapy
›4-7 days maximum of failed medical therapy before surgery
›Elective
›Steroid-dependent disease after biologic failure
›Dysplasia or malignancy
›Intractable disease with impaired quality of life
›Surgical options
›Subtotal colectomy with end ileostomy: procedure of choice in acute setting
›Minimizes operative complexity in sick patient
›Preserves future restorative proctectomy option
›Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA)
›Elective staged procedure
›Avoids permanent stoma in most patients