What are the treatment options for managing ulcerative colitis?

Treatment Options for Managing Ulcerative Colitis

The first-line treatment for mild to moderate ulcerative colitis is 5-aminosalicylate (5-ASA) compounds, with specific regimens determined by disease extent and severity. 1, 2

Treatment Based on Disease Extent

Proctitis (Disease Limited to Rectum)

• Mesalamine 1g suppositories once daily is the preferred initial treatment for mild to moderate proctitis 1
• Mesalamine foam or enemas are alternatives, but suppositories deliver the drug more effectively to the rectum and are better tolerated 1
• Topical mesalamine is more effective than topical steroids 1
• Combining topical mesalamine with oral mesalamine enhances effectiveness 1, 3

Left-Sided Colitis (Disease Up to Splenic Flexure)

• Combination therapy with topical mesalamine 1g daily plus oral mesalamine ≥2.4g daily is most effective as first-line treatment 1, 3
• Once-daily dosing of oral mesalamine is as effective as divided doses and improves adherence 1
• Topical mesalamine is more effective than topical corticosteroids 1
• If no improvement occurs with combination therapy, oral prednisolone 40mg daily should be initiated with gradual tapering over 8 weeks 1, 3

Extensive Colitis (Disease Beyond Splenic Flexure)

• Oral mesalamine ≥2.4g daily or balsalazide 6.75g daily is effective first-line therapy 1
• Combined with rectal mesalamine 1g daily for enhanced effectiveness 1
• Prednisolone 40mg daily is appropriate when prompt response is required or when mesalamine has been unsuccessful 1
• Prednisolone should be tapered gradually over 8 weeks to avoid early relapse 1, 3

Step-Up Therapy for Inadequate Response

For Patients Not Responding to First-Line Therapy

• Patients with mild-moderate UC refractory to optimized oral and rectal 5-ASA should add either oral prednisone or budesonide MMX 1
• Budesonide MMX 9mg/day is effective for left-sided disease but not extensive colitis 1
• Long-term treatment with steroids is undesirable; patients with chronic active steroid-dependent disease should be treated with azathioprine 1.5-2.5mg/kg/day or mercaptopurine 0.75-1.5mg/kg/day 1

For Moderate to Severe Disease

• Infliximab is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy 4
• The recommended dose is 5mg/kg given as an intravenous induction regimen at 0,2, and 6 weeks followed by maintenance regimen of 5mg/kg every 8 weeks 4

Important Clinical Considerations

• Always exclude infectious causes before attributing symptoms to UC flare and escalating therapy 3
• Proximal constipation can paradoxically worsen diarrhea symptoms in distal UC and should be addressed with appropriate laxatives 1, 3
• Combination therapy (topical plus oral) is more effective than either treatment alone for controlling symptoms in distal disease 3, 5
• For mild to moderate UC, 5-ASA can induce endoscopic remission to a similar extent as anti-TNF therapy 6
• Histologic remission is achieved after induction in up to 45% of patients treated with topical 5-ASA and 30% with oral formulations 6
• Despite advances in medical therapies, approximately 20% of patients with UC are hospitalized within 5 years of diagnosis, and approximately 7% undergo colectomy 2
• Patients with UC require monitoring of symptoms and biomarkers of inflammation (e.g., fecal calprotectin), and colonoscopy at 8 years from diagnosis for surveillance of dysplasia 2, 7

5-ASA Formulations and Dosing

• Low dose = <2g/day of mesalamine 1
• Standard dose = 2-3g/day of mesalamine 1
• High dose = >3g/day of mesalamine 1
• Different formulations include pH-dependent release (Delzicol, Asacol-HD), time-dependent release (Pentasa), MMX mesalamine (Lialda), and diazo-bonded 5-ASA (balsalazide, olsalazine) 1
• Once-daily dosing is as effective as divided doses and improves adherence 1, 8