in Inflammatory Bowel ... Disease (IBD) -

and Inflammatory Bowel ... Disease (IBD) ... in Sx, but not disease ... meal • Crohn's Disease ... Focuses on diverse

IBD - Assessment of Lack of Response (sLOR) - Differential Diagnosis Non-inflammatory mechanisms: • IBS • Fibrostenotic strictures • Malignancy • Other (bile salt diarrhea, SIBO, lactose) Inflammatory mechanisms, Non-IBD related: • Infection • Ischaemic Inflammatory mechanisms, IBD-related: • Immunogenicity failure: immune drug clearance - ADA • PK failure: non-immune drug clearance - Inflammatory burden - Low albumin level - Fecal loss - Non-adherence • PD failure Dr. Jean Donet @JeanDonet #IBD #sLOR #LossOfResponse #Differential #Diagnosis #Causes #Inflammatory #BowelDisease

IBD and Pregnancy: Managing Flares Laboratory Values - Endoscopy - Radiologic imaging - Surgery - Medication #inflammatory #boweldisease #IBD #Pregnancy #Flares #management #gastroenterology

Thiopurines in IBD Indications: • Steroid-sparing agents indicated for maintenance of remission in UC and CD • Not induction agents. Slow onset of action (~12 weeks) • In combination with aTNF -> increase aTNF levels and decrease Ab formation -> better outcomes Metabolism: • Thiopurine S-methyltransferase (TPMT) • 6-TGN: active metabolite. Associated to drug efficacy and Bone Marrow toxicity • 6-MMP: inactive metabolite. Associated to Hepatotoxicity • "Shunters" or "Hypermethylators": preferentially metabolyze 6MP towards 6-MMP Dosage: • Based on TPMT activity. NUDT15 gene mutations associated to leukopenia (Asian populations) • Homozygous low activity: avoid thiopurines. Highest risk for severe and fatal myelosupression • Heterozygous or intermediate activity: decrease dose by 50% • Homozygous high or normal activity: AZA 2-3mg/kg and MP 1-1.5mg/kg TDM (thiopurine metabolites): • 4 to 6 weeks after start and after dose changes/allopurinol addition • Reactive • when determination of compliance is needed • 6TG 235-450 associated to good clinical response. - low 6TG/low 6MMP: increase dose by 25-50mg. - low 6TG/high 6MMP ("shunter"): decrease dose by 25% and add allopurinol 100mg qd or dose splitting - Absent or minimal 6TG and 6MMP: non-compliant. - High 6TG and not responding: - switch MOA. 6TG> 125 may be adequate to achieve good levels of IFX. Safety: • Serious Infections: lower rate when compared to aTNF. (*But less effective drugs). GI intolerance. Pancreatitis (dose-independent, 3%) • Bone marrow toxicity: linked to high 6TG>400. Monitor CBC q 1-2 weeks initially and then q3m • Hepatotoxicity: linked to high 6MMP > 5700 • NMSC. Lymphomas are ↑ but uncommon (>aTNF). Risk becomes ↑ after 1y of exposure. Absolute risk ↑ > 50yo. HSTC lymphoma (potentially fatal): men < 35 yo on Rx > 2y are at ↑ risk. EBV seroconversion is a concern-most adults already EBV+ Dr. Jean Donet @JeanDonet #Thiopurines #IBD #Inflammatory #BowelDisease #Management #Treatment

Small and Large Bowel ... Inflammatory bowel ... disease (Crohn’ ... disease Malrotation ... #Small #Large #Bowel

Ischemia • Short Bowel ... Resection Large Bowel ... • Irritable Bowel ... • Inflammatory Bowel ... • Irritable Bowel

Colitis vs Crohn's Disease ... around the large bowel ... colon Crohn’s Disease ... 80%) have small bowel ... given segments of bowel

Fibrosis • Celiac Disease ... • Inflammatory Bowel ... Disease • Overfeeding ... • Short Bowel ... • Irritable Bowel

Inflammatory bowel ... disease: Crohn ... disease compared ... colitis #Crohns #Disease