How difficult is it to achieve a Mayo score of 1 from 3 in a patient with moderate ulcerative colitis through endoscopic means?

Achieving Mayo Endoscopic Score Improvement from 3 to 1 in Ulcerative Colitis

Achieving endoscopic improvement from Mayo score 3 to Mayo score 1 is moderately difficult but achievable in approximately 50-62% of patients with moderate-to-severe ulcerative colitis treated with advanced therapies within 8-30 weeks. 1, 2

Evidence from Clinical Trials with Advanced Therapies

Infliximab Data

• In the ACT-1 and ACT-2 trials, patients starting with Mayo endoscopic subscore 2 or 3 achieved mucosal healing (defined as Mayo endoscopic subscore 0 or 1) in 59-62% at Week 8 and 45-50% at Week 30 with infliximab 5 mg/kg treatment 1
• These rates represent the combined population of patients with both Mayo 2 and Mayo 3 at baseline, meaning those starting at Mayo 3 specifically face a more challenging trajectory 1

Adalimumab Data in Pediatric Population

• In pediatric ulcerative colitis patients with Mayo endoscopic subscore 2-3 at baseline, endoscopic improvement (Mayo endoscopy subscore ≤1) was achieved in 39-52% at Week 52 depending on dosing frequency 2
• This demonstrates that even with sustained therapy, achieving endoscopic improvement from severe disease requires months of treatment 2

Clinical Trial Definitions and Context

Baseline Disease Severity

• Clinical trials for moderate-to-severe UC specifically enroll patients with Mayo Clinic Score 6-12 and an endoscopic subscore of 2 or 3, meaning Mayo 3 represents the most severe endoscopic disease included in these studies 3
• Mayo endoscopic subscore 3 is defined as severe disease with spontaneous bleeding and ulcerations, representing the highest degree of mucosal inflammation 3

Target Definition

• Endoscopic improvement is consistently defined across guidelines and trials as achieving Mayo endoscopic subscore 0 or 1 3
• This represents a 2-point improvement from baseline Mayo 3, requiring resolution of spontaneous bleeding and ulcerations 3

Factors Affecting Difficulty of Achievement

Time Course Considerations

• The probability of achieving mucosal healing increases with time: cumulative probabilities in one real-world study were 26% at 26 weeks, 52% at 52 weeks, and 70% at 76 weeks when treating to target with endoscopic monitoring 4
• Early endoscopic response (Week 8) predicts better long-term outcomes, but many patients require extended therapy beyond initial induction 1

Prognostic Indicators

• Patients with Mayo 3 at baseline who fail to show improvement face significantly higher colectomy rates 1
• The UCEIS scoring system may better capture incremental improvements than Mayo score alone, as Mayo 3 does not distinguish between deep ulcers and shallow ulcers during healing 5
• When UCEIS ≥7 at baseline, patients face particularly poor prognosis with higher colectomy rates 6

Practical Clinical Approach

Treatment Strategy

• Use higher or intermediate efficacy advanced therapies (TNF antagonists, JAK inhibitors, IL-12/23 antagonists, or S1P modulators) rather than lower efficacy options for patients with Mayo 3 disease 3
• Consider extended induction or dose escalation for patients with severe disease (Mayo 3) who show inadequate initial response 3

Monitoring Timeline

• Assess symptomatic response within 3 months of initiating advanced therapy 3
• Perform endoscopic reassessment at 6-12 months to evaluate for endoscopic improvement/remission 3
• If endoscopic activity persists (Mayo score remains 2-3), adjustment of medical therapy is associated with improved rates of achieving mucosal healing 4

Common Pitfalls and Caveats

Scoring System Limitations

• The Mayo endoscopic subscore lacks sensitivity to detect partial improvements, as it only evaluates the most severely affected segment and uses only 4 possible scores 7
• A patient may show substantial healing in multiple colonic segments but still be scored as Mayo 3 if one area remains severely inflamed 7, 8
• The UCEIS may better capture incremental improvements during healing, particularly when ulcers become smaller and shallower but haven't completely resolved 5

Clinical-Endoscopic Discordance

• Patients may achieve clinical remission (symptomatic improvement) while still having Mayo 3 endoscopic disease, requiring continued therapy escalation 3
• Conversely, fecal calprotectin >150-250 mg/g can help identify persistent endoscopic inflammation in asymptomatic patients, though false positive rates exist 3

Treatment Persistence

• Approximately 60% of patients starting with endoscopic disease activity can achieve mucosal healing with systematic endoscopic monitoring and treatment adjustment 4
• This requires commitment to "treating to target" with repeated endoscopic assessments and willingness to escalate therapy when Mayo 3 persists 4