What are the latest treatment options for a patient with inflammatory bowel disease (IBD), including ulcerative colitis or Crohn's disease, presenting with symptoms of abdominal pain, diarrhea, and weight loss?

Latest Treatment Options for Inflammatory Bowel Disease

For patients with IBD presenting with abdominal pain, diarrhea, and weight loss, initiate treatment based on disease severity and type: start with high-dose mesalazine (4g daily) for mild ulcerative colitis, corticosteroids for moderate-severe disease, and escalate to anti-TNF biologics (infliximab or adalimumab) for refractory cases, with newer options including JAK inhibitors (upadacitinib, tofacitinib), IL-12/23 inhibitors (ustekinumab, risankizumab), and integrin antagonists (vedolizumab) available as second-line advanced therapies. 1, 2, 3

First-Line Medical Management

Ulcerative Colitis

• Topical mesalazine combined with oral mesalamine (4g daily) is the first-line treatment for active distal colitis, providing prompt symptom relief 1
• Topical corticosteroids can be added to enhance efficacy in patients with distal disease 1
• For maintenance therapy, continue high-dose mesalazine (4g daily) to reduce relapse rates and lower colorectal cancer risk 1

Crohn's Disease

• High-dose mesalazine (4g daily) may be sufficient as initial therapy for patients with mild ileocolonic Crohn's disease 1
• Corticosteroids are indicated for induction of remission in patients with moderate-severe Crohn's disease 1
• Limit corticosteroid duration to 7-10 days maximum, as extending beyond this provides no additional benefit 4

Second-Line Immunosuppressive Therapy

When first-line treatments fail or for steroid-dependent disease:

• Azathioprine (1.5-2.5 mg/kg/day) or mercaptopurine (0.75-1.25 mg/kg/day) should be used for steroid-dependent disease and maintenance of remission 1
• Methotrexate 25mg IM weekly for up to 16 weeks, followed by 15mg weekly is effective for chronic active Crohn's disease 1

Critical Pitfall: Patients with TPMT or NUDT15 deficiency are at increased risk of severe myelotoxicity with azathioprine; consider genetic testing before initiation and use reduced dosages in heterozygous deficiency 5

Advanced Biologic and Small Molecule Therapies

Anti-TNF Agents (First-Line Biologics)

• Infliximab, adalimumab, and golimumab are reserved for moderate to severe disease refractory to or intolerant of conventional therapy 1, 2
• Anti-TNF agents are typically the first biologic prescribed due to lower costs with biosimilars and good effectiveness/safety profile 2
• FDA Warning: Patients receiving TNF-blockers have increased risk of serious infections, lymphoma, and hepatosplenic T-cell lymphoma, particularly adolescent and young adult males with Crohn's disease or ulcerative colitis receiving concomitant azathioprine 6

Newer Biologic Options

• Vedolizumab (anti-integrin) prevents leukocyte homing to the gut, offering gut-specific immunosuppression with reduced systemic effects 2, 7
• Ustekinumab (IL-12/23 inhibitor) is approved for Crohn's disease, blocking the interleukin 12/23 pathway 2
• Risankizumab (selective IL-23 antagonist) is approved for Crohn's disease 3
• Mirikizumab (selective IL-23 antagonist) is approved for ulcerative colitis 3

Oral Small Molecules

• Tofacitinib (JAK inhibitor) is approved for ulcerative colitis 2, 3
• Upadacitinib (JAK inhibitor) is approved for both Crohn's disease and ulcerative colitis 3
• Ozanimod and etrasimod (S1P receptor modulators) are both approved for ulcerative colitis 3

These oral agents offer an alternative to subcutaneous injection or intravenous infusion for moderate-to-severe disease 7, 3

Management of Acute Severe Ulcerative Colitis

For patients presenting with severe symptoms (bloody stool frequency ≥6/day plus tachycardia, fever, anemia, or elevated inflammatory markers):

• Immediately initiate intravenous corticosteroids (hydrocortisone 100mg four times daily OR methylprednisolone 40-60mg daily) without waiting for stool culture results 4
• Administer adequate IV fluids with potassium supplementation of at least 60mmol/day to prevent hypokalemia and toxic dilatation 4
• Initiate subcutaneous low-molecular-weight heparin for thromboprophylaxis immediately—rectal bleeding is not a contraindication 4
• Assess response by day 3; consider rescue therapy with infliximab or ciclosporin for non-responders 1, 4

Critical Pitfall: Delaying corticosteroid treatment while waiting for stool microbiology results should be avoided, and extending IV corticosteroids beyond 7-10 days without escalating to rescue therapy or surgery increases morbidity 4

Surgical Considerations

Surgery remains an integral part of multidisciplinary IBD management despite medical advances:

• Subtotal colectomy with ileostomy is the procedure of choice for acute severe ulcerative colitis with massive hemorrhage or non-response to medical treatment 4
• For Crohn's disease, resections should be limited to macroscopic disease and be conservative 1
• Joint management by gastroenterologist and colorectal surgeon is essential for patients with severe disease 1, 4
• Emergency surgical exploration is mandatory for hemodynamically unstable patients, colonic perforation, toxic megacolon with perforation, or massive bleeding 4

Important Note: The risk of first CD surgery after 10 years decreased from 44% to 21% in recent decades, and colectomy rates in UC have similarly declined, likely due to anti-TNF therapy and improved multidisciplinary management 2

Peri-operative Management

For patients requiring surgery while on medical therapy:

• Biological treatment can be continued during the peri-operative period 2
• Pre-operative nutritional assessment and intervention are imperative to reduce postoperative morbidity 2
• Physical and psychological prehabilitation should be implemented 2

Maintenance and Long-Term Management

• Lifelong maintenance therapy is generally recommended for all patients, especially those with left-sided or extensive disease 1
• Maintenance therapy reduces the risk of colorectal cancer in IBD patients 1
• Regular monitoring for complications, extraintestinal manifestations, and surveillance for colorectal cancer is essential 1

Positioning of Newer Therapies

The therapeutic approach should prioritize:

1. Disease severity and location determine initial therapy choice
2. Prior treatment failures guide selection among advanced therapies
3. Patient-specific factors including comorbid immune-mediated diseases, pregnancy considerations, and patient preferences influence medication selection 3
4. Comparative effectiveness and safety in the context of individual patient's risk profile should drive decision-making 3