What are the conservative management options for Ulcerative Colitis (UC)?

From the Guidelines

Conservative management of colitis should prioritize the use of standard-dose mesalamine or diazo-bonded 5-ASAs for induction and maintenance of remission, as recommended by the American Gastroenterological Association (AGA) guidelines 1. The AGA guidelines, published in 2019, provide a framework for managing mild-to-moderate ulcerative colitis using the GRADE framework and adhering to the standards set forth by the Institute of Medicine 1. Key considerations in conservative management include:

• Use of combined oral and rectal 5-ASA in patients with extensive disease to improve rates of induction of remission
• Escalation to high-dose oral with rectal 5-ASA in patients with suboptimal response to standard-dose therapy
• Early use of combined oral and rectal 5-ASA in patients with moderate symptoms
• Treatment of proctosigmoiditis or proctitis with topical mesalamines rather than oral 5-ASA
• Use of rectal corticosteroids enemas or foams in patients with suboptimal response or intolerance to rectal mesalamine
• Escalation of therapy to oral prednisone or budesonide MMX in patients with inadequate response to optimized 5-ASA It is essential to note that the AGA makes no recommendation for the use of probiotics, curcumin, or fecal microbiota transplantation (FMT) in patients with mild-moderate UC due to evidence gaps, as these modalities may delay proven effective therapy and worsen symptoms or complications 1. Regular monitoring and follow-up are crucial to assess disease activity and treatment effectiveness, and patients should be aware of warning signs that require immediate medical attention.

From the FDA Drug Label

14 CLINICAL STUDIES

14.1 Adults with Mildly to Moderately Active Ulcerative Colitis Induction of Remission Two similarly designed, randomized, double-blind, placebo-controlled trials (Study 1, NCT00503243 and Study 2, NCT00548574) were conducted in 517 adult patients with mildly to moderately active ulcerative colitis The primary efficacy endpoint in both trials was to compare the percentage of patients in remission after 8 weeks of treatment for the mesalamine delayed-release tablets treatment groups versus placebo Remission was defined as an Ulcerative Colitis Disease Activity Index (UC-DAI) of ≤1, with scores of zero for rectal bleeding and for stool frequency, and a sigmoidoscopy score reduction of 1 point or more from baseline. In both studies, the mesalamine delayed-release tablets dosages of 2.4 g and 4.8 g once daily demonstrated superiority over placebo in the primary efficacy endpoint

Conservative Management of Colitis:

• Mesalamine delayed-release tablets at dosages of 2.4 g and 4.8 g once daily have been shown to be effective in inducing remission in adult patients with mildly to moderately active ulcerative colitis 2.
• The primary efficacy endpoint was the percentage of patients in remission after 8 weeks of treatment.
• Remission was defined using the Ulcerative Colitis Disease Activity Index (UC-DAI) with specific criteria for rectal bleeding, stool frequency, and sigmoidoscopy score reduction.
• Both dosages of mesalamine delayed-release tablets demonstrated superiority over placebo in achieving remission 2.

From the Research

Conservative Management of Colitis

• The goal of conservative management in colitis is to induce and maintain remission of symptoms and mucosal inflammation 3, 4.
• Treatment options depend on the severity and extent of the inflammation, with topical 5-aminosalicylic acid (5-ASA) being the treatment of choice for mild to moderate distal ulcerative colitis 3, 4.
• Oral aminosalicylates are effective in both distal and extensive mild to moderate disease, but may have lower rates of remission in distal disease compared to topical 5-ASA 3.
• Corticosteroids, such as budesonide and beclomethasone dipropionate, can be used as an alternative to 5-ASA therapy or in combination with 5-ASA for more severe disease 3, 5.

Medical Therapy for Severe Ulcerative Colitis

• Intravenous glucocorticosteroids, such as methylprednisolone, are the mainstay of medical therapy for severe ulcerative colitis 6.
• Second-line strategies for steroid-refractoriness include prolonged glucocorticosteroids treatment, oral ciclosporin, infliximab, or surgery 6.
• A study found that approximately 80% of patients with severe ulcerative colitis responded to short-term medical treatment, with only 5% requiring colectomy in the follow-up period 6.

Role of Mesalamine in Ulcerative Colitis

• Mesalamine is considered a first-line therapy for ulcerative colitis, with clinical trials confirming its efficacy and safety in patients with mild to moderate disease 7.
• Higher doses of mesalamine (>2.4g/d) achieve significantly higher rates of clinical and endoscopic remission, with a decreased risk of relapse 7.
• A randomized controlled trial found that the addition of mesalamine to corticosteroids did not provide a significant benefit over corticosteroids alone in hospitalized patients with acute severe ulcerative colitis 5.