What is the initial treatment for a patient with colitis?

Initial Treatment for Colitis

Start with topical mesalamine 1 g suppository once daily plus oral mesalamine 2.4-4.8 g/day for newly diagnosed ulcerative colitis, tailored to disease extent and severity. 1

Treatment Based on Disease Extent and Severity

Mild Disease (Proctitis or Limited Colitis)

• Topical mesalamine 1 g suppository once daily is the preferred first-line therapy for proctitis, as it delivers medication more effectively to the rectum than foam or enemas and demonstrates superior tolerability 1
• Add oral mesalamine ≥2.4 g/day to enhance effectiveness beyond either therapy alone 1
• Topical mesalamine is more effective than topical corticosteroids for distal disease 1, 2
• For left-sided colonic Crohn's disease of mild to moderate activity, topical mesalamine may be effective 3

Moderate Disease (Extensive Colitis)

• Combination therapy with topical mesalamine (≥1 g/day) plus oral mesalamine (≥2.4 g/day) is recommended 1
• If no improvement within 10-14 days or symptoms worsen, increase oral mesalamine to 4.8 g/day and continue for up to 40 days before determining treatment failure 1
• For moderate ileocolonic Crohn's disease, oral prednisolone 40 mg daily is appropriate if mesalamine fails 3
• Budesonide 9 mg daily is an option for isolated ileo-caecal Crohn's disease with moderate activity, though marginally less effective than prednisolone 3

Severe Disease Requiring Hospitalization

• Intravenous corticosteroids (hydrocortisone 400 mg/day or methylprednisolone 60-100 mg four times daily) are the mainstay of initial therapy 3
• Bolus injection is as effective as continuous infusion 3
• Higher doses provide no additional benefit; treatment should not extend beyond 7-10 days 3
• IV fluid and electrolyte replacement with potassium supplementation of at least 60 mmol/day is essential, as hypokalaemia can promote toxic dilatation 3
• Subcutaneous prophylactic low-molecular-weight heparin is required to reduce thromboembolism risk 3
• Unprepared flexible sigmoidoscopy with biopsy should be performed to confirm diagnosis and exclude cytomegalovirus infection 3
• Stool cultures and Clostridium difficile toxin assay are mandatory, as C. difficile is more prevalent in severe UC and associated with increased mortality 3

Treatment Escalation for Inadequate Response

After Failed Mesalamine Therapy

• Add oral prednisolone 40 mg daily if inadequate response to optimized mesalamine after 40 days 1
• Taper prednisolone gradually over 6-8 weeks to prevent early relapse; more rapid reduction is associated with early relapse 3, 1

Steroid-Refractory Severe Disease (Day 3 Assessment)

• Consider second-line medical therapy with infliximab, vedolizumab, or ciclosporin early (on or around Day 3 of steroid therapy) to avoid delayed surgery and associated high morbidity 3
• For steroid-refractory cases, infliximab 5 mg/kg is effective but should be avoided in patients with obstructive symptoms 3
• Ciclosporin 2 mg/kg/day IV is an alternative, particularly for patients who should avoid steroids (steroid psychosis, osteoporosis, poorly controlled diabetes) 3
• Monotherapy with IV ciclosporin 4 mg/kg/day is as effective as IV methylprednisolone 40 mg/day for acute severe UC 3

Crohn's Disease-Specific Considerations

Active Ileocolonic or Colonic Crohn's Disease

• High-dose mesalazine 4 g/daily may be sufficient initial therapy for mild ileocolonic disease 3
• Sulphasalazine 4 g daily is effective for active colonic disease but not recommended as first-line therapy due to high incidence of side effects 3
• Metronidazole 10-20 mg/kg/day, though effective, is not usually recommended as first-line therapy but has a role in selected patients with colonic or treatment-resistant disease 3
• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day may be used as adjunctive therapy and as a steroid-sparing agent, but slow onset of action precludes use as sole therapy 3

Fistulating and Perianal Crohn's Disease

• Metronidazole 400 mg three times daily and/or ciprofloxacin 500 mg twice daily are appropriate first-line treatments for simple perianal fistulae 3
• Azathioprine or mercaptopurine are potentially effective for simple perianal or enterocutaneous fistulae where distal obstruction and abscess have been excluded 3

Immune Checkpoint Inhibitor-Induced Colitis

Grade 1 (Mild Diarrhea)

• Continue immune checkpoint inhibitor therapy 3
• Conservative therapy alone is advised; avoid immunosuppressants including topical forms like budesonide due to lack of supporting evidence 3
• Supportive care with loperamide may be used if infection is ruled out 3

Grade 2 (Moderate Diarrhea: 4-6 stools/day over baseline)

• Hold immune checkpoint inhibitor until recovery to Grade 1 3
• Administer corticosteroids starting with 1 mg/kg/day prednisone or equivalent until symptoms improve to Grade 1, then taper over 4-6 weeks 3
• Endoscopic evaluation with colonoscopy is highly recommended to stratify patients for early biologic treatment based on endoscopic findings 3
• Consider adding infliximab or vedolizumab for corticosteroid-refractory cases (no decrease by one grade in 72 hours) or those with high-risk endoscopic features 3

Grade 3-4 (Severe: ≥7 stools/day or life-threatening)

• Administer corticosteroids 1-2 mg/kg/day prednisone or equivalent (consider IV methylprednisolone if concern for upper GI inflammation) 3
• Consider early introduction of infliximab or vedolizumab in addition to steroids for high-risk endoscopic features or inadequate response to steroids after 3 days 3
• Hospitalization is indicated for dehydration or electrolyte imbalance 3
• Permanently discontinue CTLA-4 agents 3

Maintenance Therapy

• Continue lifelong maintenance therapy with mesalamine after achieving remission to prevent relapse 1
• Maintenance therapy may reduce colorectal cancer risk, especially in patients with left-sided or extensive disease 1
• Monitor renal function by checking eGFR before starting mesalamine, after 2-3 months, and then annually 1

Critical Safety Monitoring

• Withdraw anticholinergic, anti-diarrhoeal, non-steroidal anti-inflammatory, and opioid drugs in severe colitis 3
• NSAID use is associated with increased risk of immune checkpoint inhibitor-induced colitis 3
• Nutritional support is appropriate if the patient is malnourished; enteral nutrition is preferred over parenteral nutrition (9% vs 35% complications) 3
• Joint management by gastroenterologist and colorectal surgeon is essential for severe disease 3