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Mechanistic Deep Dive
Pathophysiology
- Genetic susceptibility (NOD2/CARD15 in CD)
- Environmental triggers
- Dysregulated mucosal immune response
- Microbiome (dysbiosis)
- Epithelial barrier dysfunction
Th17 + IL-23 Axis
- Central in IBD inflammation
- Target for ustekinumab, risankizumab, mirikizumab
S1P Receptor in IBD
- Lymphocyte trafficking
- Ozanimod, etrasimod inhibit egress from lymph nodes
JAK-STAT Pathway
- Multiple cytokine signaling
- Tofacitinib, upadacitinib pan-JAK
Recent Trials & Updates
LUCENT-1, LUCENT-2 (2023) â Mirikizumab UC
- IL-23p19 selective
- FDA approval 2023
ADVANCE, MOTIVATE (2022) â Risankizumab CD
- IL-23p19 selective
- FDA approval 2022
U-EXCEL, U-EXCEED (2023) â Upadacitinib CD
- JAK inhibitor
- FDA approval 2023
TRUE NORTH (2020) â Ozanimod UC
- S1P modulator
- FDA approval 2021
ELEVATE UC (2023) â Etrasimod
- S1P modulator
- FDA approval 2023
CALM Trial â Treat to Target
- Mucosal healing-driven
- Improved outcomes
High-Yield Specialist Points
Drug Sequencing
- After biologic failure, next-line consideration
- Mechanistic differences may help
- Bio-naive vs bio-experienced have different responses
Antibody Levels + Drug Monitoring
- Infliximab levels + anti-drug antibodies
- Personalized dosing
- â Doses for low levels + neutralizing antibodies
Vaccination Pre-Biologic
- Live vaccines avoided
- Inactivated: flu, pneumococcal, HBV
- Document immunity
Pregnancy + Biologics
- Maintain TNF inhibitors through 3rd trimester (last dose 4-6 weeks pre-delivery for newer)
- Vedolizumab: less placental transfer
- Avoid live vaccines in infant first 6-12 months
Anti-TNF Side Effects
- Infections (TB reactivation â screen)
- Demyelination (caution MS)
- HF worsening
- Drug-induced lupus
- Allergic reactions (especially anti-chimeric infliximab)
- Possible malignancy (lymphoma in young)
JAK Inhibitor Black Box
- Cardiovascular events
- Thrombotic events
- Malignancy
- Mortality
- More in ⥠50, smokers, RA history
- Monitor: lipids, CBC, CK
S1P Modulator Side Effects
- Bradyarrhythmia (first dose)
- Macular edema
- Lymphopenia
- Liver enzymes
- Infections
Strictureplasty (CD)
- Preserve bowel
- Alternative to resection for short strictures
Multidisciplinary Care
- Gastroenterologist + colorectal surgeon + dietitian + IBD nurse + mental health + pharmacist
IBD + Cancer
- â CRC (long-standing colitis)
- Lymphoma (especially with thiopurines)
- Skin cancer (immunosuppression)
- Surveillance
IBD Microbiome Therapies
- FMT trials (mixed results)
- Specific probiotics
- Diet-based interventions (Crohnâs exclusive enteral nutrition pediatric)
Pediatric IBD
- Higher proportion with early-onset
- Growth failure concern
- Specific pediatric trials
- Aggressive early biologic often
Pearls
- CD vs UC hallmark differences must memorize
- PSC strongly UC-associated
- Mesalamine + topical for distal UC
- Top-down with early biologic for moderate-severe
- Vedolizumab gut-selective (less systemic IS)
- Anti-IL-23 selective (risankizumab, mirikizumab) newer
- JAK inhibitors + S1P modulators for UC oral options
- Pregnancy: continue most biologics; stop MTX
- CRC surveillance 8-10 yr after onset
- Vaccinate before biologic (esp live)