What is the best treatment approach for a patient with ulcerative colitis?

Treatment of Ulcerative Colitis

For mild-to-moderate ulcerative colitis, start with oral mesalamine 2.4-4.8 g/day combined with rectal mesalamine, and for moderate-to-severe disease, initiate infliximab or vedolizumab as first-line biologic therapy with or without an immunomodulator. 1, 2, 3

Disease Severity Assessment

Before selecting treatment, classify disease by:

• Location: Proctitis (rectum only), left-sided (up to splenic flexure), or extensive (beyond splenic flexure) 2
• Severity: Mild (≤4 stools/day, minimal blood), moderate (4-6 bloody stools/day), or severe (≥6 bloody stools/day plus systemic signs like fever, tachycardia, anemia) 2

Treatment Algorithm by Disease Severity

Mild-to-Moderate Disease

For ulcerative proctitis:

• Use mesalamine 1 g suppositories once daily as first-line monotherapy 2, 3
• Suppositories deliver medication more effectively to the rectum than foam or enemas and are better tolerated 3
• Response rates reach 40-70% with remission rates of 15-20% 2

For left-sided or extensive disease:

• Combine oral mesalamine 2.4-4.8 g/day with rectal mesalamine 1 g enemas daily 1, 2, 3
• This combination is superior to either oral or topical therapy alone 3
• Higher doses (>3 g/day up to 4.8 g/day) show superior efficacy in moderate disease without increased toxicity 2
• Once-daily dosing is as effective as divided dosing and improves adherence 2
• Rectal mesalamine enemas are superior to rectal corticosteroids for left-sided disease 2

Assess response at 4-8 weeks:

• If no symptomatic improvement occurs by this timeframe, this constitutes 5-ASA failure and requires escalation 2
• If symptoms deteriorate, rectal bleeding persists beyond 10-14 days, or sustained relief has not been achieved after 40 days of appropriate 5-ASA therapy, escalate treatment 3

Moderate-to-Severe Disease

For 5-ASA-refractory disease:

• Initiate oral prednisolone 40 mg daily as bridge therapy while simultaneously starting a biologic agent 1, 2, 3
• Evidence shows 40 mg/day is more effective than 20 mg/day, with no additional benefit from doses higher than 40-60 mg/day but increased adverse effects 3
• Taper prednisolone gradually over 8 weeks according to severity and patient response, as more rapid reduction is associated with early relapse 4, 3

First-line biologic selection:

• Infliximab and vedolizumab are preferred first-line biologics in biologic-naïve patients 4, 1, 3
• Standard infliximab dosing is 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks for maintenance 5
• For patients who respond and then lose response, consider increasing infliximab to 10 mg/kg 5
• Patients who do not respond by week 14 are unlikely to respond with continued dosing and should discontinue 5

Combination therapy:

• Combination therapy (biologic + immunomodulator such as azathioprine or mercaptopurine) is more effective than monotherapy 4, 1, 3
• However, patients with less severe disease or those averse to medication side effects may opt for monotherapy 4

Alternative biologics:

• Adalimumab and golimumab are options but network meta-analysis suggests they may be less effective than infliximab or vedolizumab as first-line therapy 4
• In patients with prior infliximab exposure, particularly those with primary non-response, vedolizumab or tofacitinib may be preferred over adalimumab or golimumab 4

Acute Severe Ulcerative Colitis (Hospitalized Patients)

Immediate management:

• Joint management by gastroenterologist and colorectal surgeon is mandatory 4, 1
• Inform patients of 25-30% chance of needing colectomy 4
• Intravenous methylprednisolone 40-60 mg/day (or hydrocortisone 400 mg/day) is the mainstay of treatment 4, 1

Supportive care:

• Record vital signs four times daily and more often if deterioration noted 4
• Maintain stool chart documenting number, character, and presence of blood 4
• Measure CBC, ESR or CRP, electrolytes, albumin, and liver function tests every 24-48 hours 4
• Daily abdominal radiography if colonic dilatation (transverse colon diameter >5.5 cm) detected at presentation 4
• IV fluid and electrolyte replacement to correct dehydration 4, 1
• Blood transfusion to maintain hemoglobin >10 g/dL 4, 1
• Subcutaneous heparin to reduce thromboembolism risk 4, 1
• Nutritional support (enteral or parenteral) if malnourished 4

For corticosteroid-refractory disease (after 3-5 days):

• Treat with either infliximab or cyclosporine for patients who prefer ongoing medical management 4
• No recommendation can be made regarding routine use of intensive versus standard infliximab dosing in this setting 4

Maintenance Therapy

Lifelong maintenance is recommended for all patients, especially those with left-sided or extensive disease: 4, 1, 3

After 5-ASA-induced remission:

• Continue mesalamine at doses ≥2 g/day indefinitely 4, 1, 3
• Higher maintenance doses (2.4 g/day versus 1.2 g/day) prolong remission, particularly in extensive disease 4, 2
• Continuing the induction dosage for an extra 4 weeks prolongs remission and reduces relapse frequency 4, 2

After biologic-induced remission:

• Continue the same agent that successfully induced remission at the same dose 2
• Patients in remission on biologics and/or immunomodulators after prior 5-ASA failure may discontinue 5-ASA 4, 1

Discontinuation considerations:

• Discontinuation may be reasonable for patients with distal disease who have been in remission for 2 years and are averse to medication 4
• However, maintenance therapy may reduce the risk of colorectal cancer 4

Critical Pitfalls to Avoid

Do not use corticosteroids for maintenance therapy:

• Corticosteroids are for induction only and should be tapered after achieving remission 2
• Never continue steroids beyond what is necessary to bridge to maintenance therapy 1

Do not delay biologic therapy in moderate-severe disease:

• Step-up approaches in patients at high risk of colectomy increase hospitalization and colectomy rates 4, 2
• In patients with moderate-severe disease activity at high risk of colectomy, use biologic agents with or without an immunomodulator early rather than gradual step-up therapy after 5-ASA failure 4

Do not underdose mesalamine:

• Efficacy is dose-dependent, with 4.8 g/day optimal for active disease 2
• Standard dosing is 2-3 g/day, but higher doses show superior efficacy in moderate disease 1, 2

Avoid unproven therapies:

• Do not use probiotics, curcumin, or fecal microbiota transplant, as they lack evidence and delay proven therapies 2

Do not use thiopurine monotherapy for induction:

• Thiopurines (azathioprine, mercaptopurine) should not be used for induction of remission but may be considered for maintenance 4

Do not use methotrexate:

• Methotrexate monotherapy, orally or subcutaneously, should not be used for induction or maintenance of remission in ulcerative colitis 4

Treatment Goals

The treatment target has evolved from achieving clinical response to achieving remission, assessed biochemically or endoscopically and histologically 3. Histologic remission is achieved after induction in up to 45% of patients with topical 5-ASA and 30% with oral formulations 3.