What are the best ranked medications for a patient with Ulcerative Colitis (UC) to achieve clinical and endoscopic remission combined, including their respective remission rates?

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Last updated: January 30, 2026 • View editorial policy

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Best Ulcerative Colitis Drugs Ranked by Combined Clinical and Endoscopic Remission

Upadacitinib ranks as the single most effective medication for achieving combined clinical and endoscopic remission in biologic-naïve UC patients, with approximately 49% achieving clinical remission and superior endoscopic improvement rates compared to all other advanced therapies. 1, 2

Ranking for Biologic-Naïve Patients

First-Tier Agents (Highest Efficacy)

1. Upadacitinib (JAK inhibitor)

  • Clinical remission: 49% (vs 10% placebo, absolute benefit 39%) 1, 2
  • Endoscopic improvement: Superior to all comparators with moderate-certainty evidence 1
  • Demonstrates moderate-to-high certainty evidence of clinically important benefit over infliximab, adalimumab, vedolizumab, etrasimod, ustekinumab, mirikizumab, tofacitinib, and filgotinib 1, 2
  • FDA restriction: Second-line only in US (requires documented TNF antagonist failure), but can be used first-line outside US 1, 2

2. Risankizumab (IL-23 antagonist)

  • Clinical remission: ~35% with moderate certainty evidence 1
  • Ranked highest among first-line options in US where JAK inhibitors are restricted 1
  • Absolute risk difference: 182 per 1000 patients (95% CI: 3 to 544) vs placebo 3
  • Histological remission: 89.4% (ranked first) 4

3. Ozanimod (S1P receptor modulator)

  • Clinical remission: ~35% with moderate certainty evidence 1
  • Co-ranked with risankizumab as most effective first-line option in US 1
  • Oral administration provides convenience advantage 3

Second-Tier Agents (Moderate-High Efficacy)

4. Guselkumab (IL-23 antagonist)

  • Clinical remission with possibly important benefit (low certainty evidence) 3
  • Histological remission: 88.3% (ranked second) 4
  • Relative risk: 1.56 (95% CI: 0.88-2.78) vs placebo 3

5. Vedolizumab (α4β7 integrin inhibitor)

  • Clinical remission: 31.3% at 52 weeks vs 22.5% for adalimumab (p=0.006) in head-to-head VARSITY trial 3
  • Mucosal healing: 39.7% vs 27.7% for adalimumab (p=0.0005) 3
  • Anti-TNF naïve patients: 79.1% response rate, 39.5% clinical remission at week 14 3
  • Ranked higher than TNF antagonists in treat-through maintenance trials 3

6. Infliximab (TNF antagonist)

  • Clinical remission at Week 8: 39% (5 mg/kg) and 32% (10 mg/kg) vs 15% placebo 5
  • Clinical remission at Week 30: 34% (5 mg/kg) and 37% (10 mg/kg) vs 16% placebo 5
  • Mucosal healing at Week 30: 50% (5 mg/kg) and 49% (10 mg/kg) vs 25% placebo 5
  • Sustained remission (Weeks 8 and 30): 23% (5 mg/kg) and 26% (10 mg/kg) vs 8% placebo 5

7. Tofacitinib (JAK inhibitor)

  • Clinical remission at Week 8: 18.5% (OCTAVE-1) and 16.6% (OCTAVE-2) vs 8.2% and 3.6% placebo 3
  • Maintenance remission at 1 year: 40.6% (10 mg BID) vs 11.1% placebo 3
  • Anti-TNF naïve patients: 23.7% remission vs 12.5% placebo (difference 11.2%) 3

Third-Tier Agents (Moderate Efficacy)

8. Etrasimod (S1P receptor modulator)

  • Ranked higher than TNF antagonists in treat-through maintenance trials 3
  • Uncertain trivial benefit vs placebo in some analyses 3

9. Mirikizumab (IL-23 antagonist)

  • Uncertain trivial benefit in biologic-naïve patients (very low certainty) 3
  • Relative risk: 1.06 (95% CI: 0.60-1.85) vs placebo 3

10. Adalimumab (TNF antagonist)

  • Clinical remission at Week 52: 29% (every other week) and 45% (weekly) in pediatric patients who responded at Week 8 6
  • Inferior to vedolizumab in head-to-head VARSITY trial (22.5% vs 31.3% at 52 weeks) 3

11. Ustekinumab (IL-12/23 antagonist)

  • Moderate efficacy but ranked lower than newer IL-23 selective agents 3

12. Filgotinib (JAK inhibitor)

  • Maintenance endoscopic improvement: 79.2% (ranked second after upadacitinib) 4
  • Lower efficacy than upadacitinib for clinical remission 1

Ranking for Biologic-Exposed Patients

First-Tier (Highest Efficacy in Refractory Disease)

1. Upadacitinib

  • Clinical remission: Absolute risk difference 653 per 1000 (95% CI: 197 to 1000) vs placebo 3
  • Relative risk: 14.05 (95% CI: 4.94-43.94) with moderate certainty evidence 3
  • Endoscopic improvement: RR 10.48 (95% CI: 1.65-24.15) 3
  • Ranked highest with moderate certainty of clinically important benefit 3, 1

2. Tofacitinib

  • Clinical remission: Absolute risk difference 473 per 1000 (95% CI: 55 to 1000) vs placebo 3
  • Relative risk: 10.45 (95% CI: 2.09-52.22) with moderate certainty evidence 3

Second-Tier (Moderate-High Efficacy)

3. Guselkumab

  • Clinical remission: Absolute risk difference 93 per 1000 (95% CI: 20 to 244) vs placebo 3
  • Relative risk: 2.86 (95% CI: 1.39-5.88) with moderate certainty evidence 3

4. Risankizumab

  • Clinical remission: Absolute risk difference 89 per 1000 (95% CI: 13 to 254) vs placebo 3
  • Relative risk: 2.77 (95% CI: 1.26-6.07) with moderate certainty evidence 3

5. Filgotinib

  • Clinical remission: Absolute risk difference 86 per 1000 (95% CI: 28 to 268) vs placebo 3
  • Relative risk: 2.71 (95% CI: 1.56-6.36) with moderate certainty evidence 3

6. Mirikizumab

  • Clinical remission: Absolute risk difference 67 per 1000 (95% CI: 15 to 158) vs placebo 3
  • Relative risk: 2.33 (95% CI: 1.30-4.16) with moderate certainty evidence 3

Third-Tier (Lower Efficacy in Refractory Disease)

7. Vedolizumab

  • Possibly trivial benefit with low certainty evidence in biologic-exposed patients 3
  • Prior anti-TNF exposure reduces probability of achieving remission (HR 0.51,95% CI 0.29-0.88) 3

8. Adalimumab

  • Possibly trivial benefit with low certainty evidence in biologic-exposed patients 3
  • Relative risk: 1.03 (95% CI: 0.50-2.13) vs placebo 3

9. Ozanimod

  • Possibly trivial benefit with low certainty evidence in biologic-exposed patients 3

10. Etrasimod

  • Possibly trivial benefit with low certainty evidence in biologic-exposed patients 3

Critical Implementation Considerations

Regulatory Restrictions

  • In the United States: JAK inhibitors (upadacitinib, tofacitinib) are FDA-restricted to second-line use after TNF antagonist failure due to cardiovascular safety data from rheumatoid arthritis populations 1, 2
  • Outside the United States: Upadacitinib can be used first-line for highest efficacy 1, 2
  • Do not use upadacitinib first-line in patients ≥65 years with cardiovascular risk factors when TNF inhibitors remain viable 2

Combination Therapy

  • Combine TNF antagonists with thiopurines or methotrexate rather than using TNF monotherapy, as combination therapy demonstrates superior remission rates 3
  • This recommendation applies to TNF antagonists specifically, not to other drug classes 3

Prior Biologic Exposure Impact

  • Prior anti-TNF exposure significantly reduces efficacy of subsequent vedolizumab (HR 0.53 for clinical remission, HR 0.51 for endoscopic remission) 3
  • IL-23 antagonists and JAK inhibitors maintain superior efficacy even in biologic-exposed populations 3

Endoscopic vs Clinical Outcomes

  • Upadacitinib demonstrates the highest rates for both clinical remission AND endoscopic improvement/mucosal healing across all comparisons 1, 4
  • Risankizumab and guselkumab rank highest for histological remission (89.4% and 88.3% respectively) 4
  • Vedolizumab shows 39.7% mucosal healing vs 27.7% for adalimumab in head-to-head comparison 3

Onset of Action

  • JAK inhibitors provide rapid onset of action compared to biologics 7
  • Oral administration (JAK inhibitors, S1P modulators) offers convenience advantage over intravenous/subcutaneous biologics 3, 7

References

1
Guideline

Most Effective UC Medication for Clinical Remission

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

2
Guideline

Upadacitinib Therapy for Biologic-Naive Ulcerative Colitis Patients

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

3
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

4
Research

Comparative Efficacy of Biologics and Small Molecule in Ulcerative Colitis: A Systematic Review and Network Meta-analysis.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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