What is the typical next step in pharmacotherapy for a patient with ulcerative colitis who has not responded to mesalamine (mesalamine) suppositories and oral mesalamine, and has not yet tried Tumor Necrosis Factor (TNF) alpha inhibitors, considering options like Entyvio (vedolizumab)?

Treatment Decision for Ulcerative Colitis After Mesalamine Failure

The Standard Next Step: Add Corticosteroids First

Before escalating to any biologic therapy (including vedolizumab or TNF inhibitors), you should add oral corticosteroids (prednisolone 40 mg daily) unless contraindicated or previously failed. 1

• The American Gastroenterological Association recommends adding oral corticosteroids before escalating to biologic therapy for patients who have failed both mesalamine suppositories and oral mesalamine 1
• This corticosteroid trial should be tapered gradually over 8 weeks according to disease severity and patient response 1
• The corticosteroid trial serves a critical purpose: it assesses steroid responsiveness, which informs subsequent treatment decisions 1
• Skipping the corticosteroid trial before biologics is not recommended in most cases unless contraindicated or previously failed 1

Critical Verification Before Escalation

Before declaring mesalamine failure, ensure the patient received an adequate trial:

• Confirm the patient received high-dose mesalamine (≥3-4.8 g/day orally) 1
• Verify that rectal therapy was combined with oral therapy for at least 10-14 days 1, 2
• Doses less than 2 grams/day are significantly less effective and do not constitute an adequate trial 2

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When to Escalate to Biologic Therapy

Biologic therapy becomes indicated in these specific scenarios:

• Failure to respond to optimized oral and rectal mesalamine plus corticosteroids 1
• Development of steroid-dependent disease (inability to taper steroids without flare) 1
• Presentation with moderate-to-severe disease activity despite corticosteroids 1

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TNF Inhibitors vs. Vedolizumab: The Evidence-Based Choice

Both Are Equally Recommended as First-Line Advanced Therapy

The 2024 American Gastroenterological Association guidelines give both TNF alpha inhibitors and vedolizumab strong recommendations with moderate-to-high quality evidence, placing them on equal footing as first-line advanced therapy. 1

• TNF alpha inhibitors (infliximab, adalimumab, golimumab) have strong evidence supporting their efficacy as first-line advanced therapy 1
• Vedolizumab achieved 47% clinical response and 17% remission at week 6 in biologic-naïve patients in the GEMINI 1 trial 1
• The European Crohn's and Colitis Organisation suggests that TNF alpha inhibitors remain the standard first-line advanced therapy, though vedolizumab represents a reasonable alternative in certain clinical contexts 1

Algorithm for Selecting Between TNF Inhibitors and Vedolizumab

Choose TNF alpha inhibitors first if:

• The patient has extraintestinal manifestations (arthritis, psoriasis, uveitis, erythema nodosum) that may respond better to TNF blockade 1
• The patient is younger and may benefit from the broader immunologic effects of TNF inhibition 1

Choose vedolizumab first if:

• The patient has significant infection risk (history of recurrent infections, latent tuberculosis, chronic viral hepatitis) 1
• The patient has history of serious infections that make systemic immunosuppression concerning 1
• The patient is elderly or has multiple comorbidities where gut-selective therapy is preferred 1

Important Nuance: Vedolizumab After TNF Failure

• In patients who have already failed one subcutaneous TNF agent (adalimumab or golimumab), vedolizumab demonstrated superior efficacy compared to switching to infliximab (another TNF agent) 3
• Clinical remission at week 14 was achieved in 49% with vedolizumab versus 26% with infliximab after subcutaneous anti-TNF failure (P = 0.001) 3
• However, your patient is biologic-naïve, so this data supports either choice as first-line 3

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Practical Implementation Considerations

If Choosing TNF Inhibitors:

• Strongly consider combining with an immunomodulator (azathioprine or methotrexate) to reduce immunogenicity and improve outcomes 1
• Infliximab, adalimumab, and golimumab are all appropriate first-line TNF inhibitors 1, 4
• Screen for latent tuberculosis and hepatitis B before initiating 5

If Choosing Vedolizumab:

• Administer 300 mg intravenously at weeks 0,2, and 6, then every 8 weeks 5
• After the first two intravenous doses, patients may switch to subcutaneous 108 mg every 2 weeks 5
• No clear recommendation exists for combination with immunomodulators for vedolizumab; monotherapy is standard 1
• Vedolizumab has gut-selective mechanism, potentially offering better safety profile in high-risk patients 1

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What NOT to Do: Common Pitfalls

• Do not use JAK inhibitors (tofacitinib, upadacitinib) as first-line advanced therapy - they are restricted to patients with prior TNF failure or intolerance in the United States 1
• Do not delay biologic therapy in steroid-dependent patients - this increases morbidity and should prompt escalation 1
• Do not skip the corticosteroid trial unless contraindicated - this violates standard treatment algorithms 1
• Do not underdose mesalamine before declaring failure - ensure ≥3-4.8 g/day was attempted with rectal therapy 1, 2

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Bottom Line: Is There a Case for Vedolizumab First?

Yes, there is a legitimate case for using vedolizumab first instead of TNF inhibitors, particularly in patients with infection risk or those without extraintestinal manifestations. 1

The 2024 guidelines place both options on equal footing, making the choice dependent on patient-specific factors rather than a hierarchical preference. The decision should be driven by:

1. Presence or absence of extraintestinal manifestations (favors TNF inhibitors) 1
2. Infection risk profile (favors vedolizumab) 1
3. Patient age and comorbidities (favors vedolizumab in elderly/high-risk) 1
4. Need for combination immunomodulator therapy (favors TNF inhibitors if willing to use combination) 1