What is the recommended treatment regimen for mesalamine in patients with mild to moderate inflammatory bowel disease, specifically ulcerative colitis?

From the Guidelines

For patients with mild to moderate ulcerative colitis, the recommended treatment regimen is to use standard-dose mesalamine (2–3 grams/day) or diazo-bonded 5-ASA, rather than low-dose mesalamine, sulfasalazine, or no treatment. This recommendation is based on the American Gastroenterological Association (AGA) clinical practice guidelines on the management of mild-to-moderate ulcerative colitis, which suggests that standard-dose mesalamine is more effective than low-dose mesalamine for inducing and maintaining remission 1.

Key Considerations

• The AGA recommends using mesalamine suppositories in patients with mild-moderate ulcerative proctitis who opt for rectal therapy, as pooled analysis of 4 RCTs showed that mesalamine suppositories are more effective than placebo in inducing remission 1.
• For patients with extensive mild-moderate ulcerative colitis, the AGA suggests adding rectal mesalamine to oral 5-ASA, as this combination has been shown to be more effective than oral 5-ASA alone 1.
• The quality of evidence for these recommendations is generally moderate, with some studies having limitations such as imprecision and heterogeneity 1.

Treatment Regimen

• The recommended dose of oral mesalamine is 2-3 grams per day, which can be divided into multiple doses.
• Rectal formulations (suppositories or enemas) can be used at a dose of 1-4 grams per day, particularly for distal disease.
• Treatment should continue indefinitely as maintenance therapy to prevent relapse, even when symptoms resolve.

Monitoring and Safety

• Patients should be monitored periodically with blood tests to check kidney function, as rare cases of nephrotoxicity can occur.
• The specific formulation (delayed-release, pH-dependent, or multi-matrix) may be selected based on the location of inflammation in the colon.
• Patients should take the medication with food to minimize gastrointestinal side effects.

Overall, the use of standard-dose mesalamine (2–3 grams/day) or diazo-bonded 5-ASA is recommended for patients with mild to moderate ulcerative colitis, with the addition of rectal mesalamine for patients with extensive disease or distal disease 1.

From the FDA Drug Label

Maintenance of Remission A mesalamine dosage of 2.4 g/day, administered as either 1.2 g twice daily or 2.4 g once daily, was evaluated for safety in three maintenance trials in patients with mildly to moderately active ulcerative colitis: a 6-month double-blind, active-controlled study (Study 3) [see Clinical Studies (14. 1)] and two 12- to 14-month open-label studies. The most common adverse reactions with mesalamine in these maintenance trials are listed in Table 3. Table 3: Adverse Reactions * in Three Trials of Maintenance of Remission in Adults with Ulcerative Colitis Mesalamine delayed-release tablets 2.4 g/day † (n=1,082) Adverse Reaction % Headache 3% Liver function test abnormal 2% Abdominal pain 2% Diarrhea 2% Abdominal distension 1% Abdominal pain upper 1% Dyspepsia 1% Back pain 1% Rash 1% Arthralgia 1% Fatigue 1% Hypertension 1%

The recommended treatment regimen for mesalamine in patients with mild to moderate ulcerative colitis is a dosage of 2.4 g/day, administered as either 1.2 g twice daily or 2.4 g once daily 2.

Key points:

• The dosage of 2.4 g/day is evaluated for safety in three maintenance trials.
• The most common adverse reactions with mesalamine in these maintenance trials include headache, liver function test abnormal, abdominal pain, diarrhea, and others.
• Mesalamine is administered as either 1.2 g twice daily or 2.4 g once daily.

From the Research

Treatment Regimen for Mesalamine in Ulcerative Colitis

The recommended treatment regimen for mesalamine in patients with mild to moderate inflammatory bowel disease, specifically ulcerative colitis, is as follows:

• The dosage of mesalamine can range from 1.5-4.8g/day, with response rates between 40%-70% and remission rates of 15%-20% in mild/moderate active disease 3.
• Studies have shown that increasing the dose of mesalamine up to 4.0g/day can be safe and effective for patients who relapse under low-dose maintenance therapy 4.
• A controlled-release mesalamine capsule formulation has been shown to be effective in treating mild to moderately active ulcerative colitis, with doses of 2-4g daily being safe and effective for inducing remission 5.
• MMX mesalamine, a once-daily tablet formulation, has been shown to effectively induce and maintain clinical remission in patients with active mild-to-moderate UC, with a similar safety profile to other oral mesalamine formulations 6.

Dosage and Efficacy

• The optimal dosages for mild-moderate distal active disease and for maintenance therapy are 4.8g/day and 2.4g/day, respectively 3.
• Patients with moderately active ulcerative colitis treated with 4.8g/d of mesalamine are significantly more likely to achieve overall improvement at week 6 compared to patients treated with 2.4g/d 3.
• There is no clear dose response above 1.5g for induction therapy, and existing data do not support a dose response above 1.5g for maintenance therapy 7.

Safety and Compliance

• Mesalamine has been shown to be safe in short-term use with a dose-response efficacy without dose-related toxicity 3.
• Once-daily dosing with multi-matrix system mesalamine 1.2g tablets may lead to optimal compliance 7.
• Mesalamine formulations have fewer side effects compared to sulfasalazine, with sulfasalazine having more frequent side effects than olsalazine, balsalazide, and mesalamine formulations 7.