treatment of Study Notes on IBD Treatment and Management

Still in use today, the 5-ASA (aminosalicylic acid) agent has two moieties:
- 5-ASA itself
- Sulfapyridine
Sulfapyridine has anti-inflammatory effects, making it valuable for rheumatologists.
Beneficial for patients with:
- Rheumatoid arthritis (primary joint disease)
- Inflammatory Bowel Disease (IBD) with joint involvement.
- Some patients find sulfapyridine's side effects off-putting.
Notably produces fluorescent yellow urine, causing patient concern, due to the sulfur moiety.

Prodrug Activation:
- Activated by colonic bacteria through the enzyme azoreductase.
Conditions Treated:
- Effective for:
- Mild to moderate ulcerative colitis (induction and maintenance of remission).
- Chemoprevention of cancer.
- Limited use in:
- Ileocolonic Crohn's disease (only).
Efficacy Limitations:
- Minimal benefit in Crohn's if restricted to the colon.
- Does not prevent relapse and is not used for acute exacerbations.

Commonly associated side effects include:
- Nausea, vomiting, abdominal pain.
- Pancreatitis.
- Liver dysfunction.
- Drug-induced connective tissue disease.
- Bone marrow suppression.
- Interstitial nephritis.
- Hemolytic anemia.
- Abnormal sperm counts.
Overall, while side effects exist, they are relatively rare compared to their benefits.

Imidazoles (e.g., metronidazole):
- Typically used in IBD due to abnormal responses to gut flora.
- Intention is to target the microbial component fueling inflammation.
Role of Ciprofloxacin in treating bacterial overgrowth, although direct immunosuppression effectiveness is questionable.
Historical treatment: Patients would be made NPO (nothing by mouth) to reduce gut bacteria, achieving temporary quiescence in disease.
Antibiotics are generally not effective in IBD except for:
- Anal rectal fistula (treated with metronidazole).
- Current studies evaluating rifaximin for efficacy.
Antibiotics can help treat complications like:
- Abscesses and small intestinal bacterial overgrowth (SIBO).

Known as the anti-inflammatory sledgehammer.
Mechanism:
- Inhibit multiple inflammatory mediators.
- Induce remission through IV or oral administration.
- Do not promote healing as they suppress immune cell function.
Side Effects:
- Frequent adverse effects include:
- Cushionoid appearance.
- Bone loss.
- Hypertension.
- Psychosis (notable experiences shared).
- Aseptic necrosis leading to bilateral hip replacements in younger patients.
- Neuropathy, myopathy, acne.
Recommended practices include:
- Starting with conservative doses (40-60 mg daily).
- Long-term treatment should be paired with biologics where possible.
- Tapering: Important to taper slowly over at least four weeks to prevent complications.
- Monitor for potential long-term dependency and resistance occurrences (up to 50% of patients).

A significant addition due to target-specific action.
Properties:
- Higher binding affinity for glucocorticoid receptors.
- First-pass metabolism in the liver reduces systemic effects.
Dosage:
- Controlled release formulation, primarily targeting terminal ileum.
- Standard dose: 9 mg/day.
Can induce and maintain remission for up to one year with minimized systemic side effects compared to traditional steroids.

Thiopurines:
- Azathioprine as a prodrug converts to 6-Mercaptopurine (6-MP).
- Both drugs can be given orally and have complex conversion processes in the body.
Measurement of the enzyme thiopurine methyltransferase (TPMT) is crucial before administration to prevent toxicity issues:
- TPMT mutations lead to decreased drug efficacy and heightened toxicity risk.
Notable risks include:
- Lymphoma risk (4-fold increase in IBD patients).
- Non-melanoma skin cancers.
- Pancreatitis (2% chance).
- Allergic reactions (2-5% risk).
Monitoring:
- Regular CBC and liver profile checks recommended during the initial phase, transitioning to monthly once stabilized.
Methotrexate:
- Typically administered in a weekly dose of 25 mg.
- Highly teratogenic, requiring caution in reproductive-aged men and women.
Cyclosporine:
- Reserved for severe steroid-refractory ulcerative colitis;
- Risks include nephrotoxicity, infections, seizures.

Types of Biologics:
- Anti-TNF Agents:
- Infliximab (chimeric), adalimumab (fully human), certolizumab (pegylated).
- MOA:
- TNF is crucial for various inflammatory pathways; targeting it decreases cytokine production.
Effects:
- Highly effective for moderate to severe Crohn's and ulcerative colitis but may require combination therapies to mitigate antibody formation against these drugs.

Examples:
- Vedolizumab, which inhibits leukocyte egress from the bloodstream to the gut.
Mechanism:
- Prevents binding to endothelial cells, aiding in reducing inflammation and clinical flares.

Target inflammatory pathways not primarily mediated by TNF.
Examples:
- Ustekinumab and more selective p19 inhibitors (e.g., risankizumab).
Effects:
- Block IL-23 with significant improvement profile in IBD patients not responding to anti-TNF agents.

Example:
- Upadacitinib (Rinvoq) ; kinase inhibitors for patients previously failed anti-TNF.
- Associated with increased risk for TB and other infections.

Mechanism:
- Block egress of T cells from lymph nodes, reducing T-cell driven gut inflammation.
Examples:
- Ozanimod and Etrasimod.

Approach depends on:
- Severity: proctitis, left-sided, or pancolitis.
- Treatment options include:
- Topical treatments plus oral agents for mild cases.
- Overall goal is induction and maintenance.
Assess comorbidities, patient engagement, and avoid NSAIDs.
Consider underlying risk factors for surgical intervention:
- Low risk treated outpatient; high risk may require inpatient treatment.
Always rule out infections, especially within the gastrointestinal tract.

Classify into low and high-risk based on disease history and current symptoms:
- Low-risk: limited anatomical involvement, no perianal disease.
- High-risk: young patients, fistulas, or extensive disease.
Avoid NSAIDs and smoking; antibiotics as needed.
Long-term strategies include regular monitoring and use of biologics for severe cases.