Mesalamine for induction of remission in patients with active mild to moderate ulcerative colitis

17 Oct 2008 Mesalamine for induction of remission in patients with active mild to moderate ulcerative colitis

Belorussian translation (courtesy of Nadejda Dobkina): http://onlinepharmacycheck.com/~doc/mesalamine-active-be

Background information of the condition:

Ulcerative Colitis (UC) is the chronic inflammation of colon and rectum.¹ There is currently no known cure for ulcerative colitis, but it can be managed by medication. Based on four randomized controlled trials (RCTs) in 892 patients with UC, 5-ASA was found to be efficacious as compared to placebo in terms of induction of remission.² Besides Mezavant®, there are 5 other mesalamine formulations available in Canada. In order to deliver mesalamine to the target site, oral tablets contain enteric coating, which allows mesalamine to be release above pH 7.

Drug (Product Monograph)³

Category: 5-aminosalicyclic acid (5-ASA)

Mechanism of Action: Mechanism of action is unknown. Multi Matrix coating prevents release of drug under pH 7.0. Once the pH is above 7.0, the hydrophilic matrix delays the release of the drug throughout the colon.

Indications: Induction of remission (clinical and endoscopic) in patients with active mild to moderate ulcerative colitis.

Dose: Each tablet contains 1.2g of mesalamine. Recommended dose is 2.4g to 4.8g per day taken once daily.

Duration: Duration of treatment in all trials is 8 weeks.

Methodology of Systematic Review

Research Question:

In double blind randomized controlled trials (DBRCTs), is Mezavant® delayed and extended release tablet as effective as other mesalamine or 5-ASA immediate release products for the induction of remission in adult patients with active, mild to moderate ulcerative colitis?

Assessment principles:

BRCTs in adult patients with active moderate to severe ulcerative colitis comparing the new formulation of Mezavant® to other mesalamine or 5-ASA immediate release formulations will be critically appraised. Trials comparing Mezavant to placebo will not be critically appraised. Benefit and harm will be assessed according to the following hierarchy of health outcomes – all cause mortality, non-fatal serious adverse events, rate of hospitalization, quality of life, proportion of patients with induced remissions, withdrawal due to adverse events and total adverse events.

Search strategy:

Databases searched include – Medline (1966-Feb. 2008), Embase (1980-Feb. 2008), and the Cochrane Central Issue 1, 2008. Key search words included: Mesalamine MMx, Mezavant, randomised or randomized clinical trials, double blind, ulcerative colitis.

Search Findings:

Three DBRCTs met the inclusion criteria.^{1, 4, 5} Lichtenstein et al compared oral Mezavant to placebo and was not critically appraised since it had no active treatment comparator arm.⁵ Prantera et al¹ compared Mezavant 3.6g/day (N = 40) to Asacol 4g/day enema treatment (N = 39) and Kamm et al4 compared oral Mezavant 2.4g/day (n = 84) and 4.8g/day (N = 85) to Asacol 2.4g/day (N = 86) and placebo -treatment arms for duration of 8 weeks. The primary outcome measure in both trials was percentage of patients in remission at 8 weeks. Prantera et al1 used Rachmilewitz Clinical Activity index and Kamm et al4 used Ulcerative Colitis Disease activity index to measure disease severity.

No DBRCT was identified comparing Mesalamine MMX (Mezavant ®) to any other mesalamine formulations available in Canada. No DBRCT was identified in elderly (age >65 years) or paediatric (age < 18 years) patients.

Results:

Mezavant 2.4g/day vs. Asacol 2.4g/day were not significantly different in terms of serious adverse events (1.2% vs. 2.3%); remission rate (40.5% vs. 32.6%); and withdrawal due to adverse events (1.2% vs. 1.2%). Mortality, hospitalization, quality of life and adverse events were not reported for each treatment group.

Mezavant 4.8g/day vs. Asacol 2.4g/day were not significantly different in terms of serious adverse events (0% vs. 2.3%) remission rate (41.2% vs. 32.6%); and withdrawal due to adverse events (0% vs. 1.2%). Mortality, hospitalization, quality of life total adverse events was not reported.

Mezavant 3.6g/day vs. Asacol 4g/day enema were not significantly different in terms of remission rate (60% vs. 48.7%); and withdrawal due to adverse events (0% vs. 2.6%) and total adverse events (15% vs. 28.2%). No patient experienced serious adverse event. Mortality, hospitalization, quality of life was not reported.

Conclusions

1. Based on one DBRCT of 8 weeks duration in 212 adult patients with active mild to moderate ulcerative colitis, Mesalamine MMX (Mezavant ®) 2.4g/day and 4.8g/day was not significantly different than Asacol 2.4g/day in terms of serious adverse events, remission rate or withdrawals due to adverse events. Mortality, hospitalization, quality of life and total adverse events were not reported.
2. Based on one DBRCT of 8 weeks duration in 79 adult patients with active mild to moderate left side ulcerative colitis, Mesalamine MMX (Mezavant ®) 3.6g/day was not significantly different than Asacol rectal suspension 4g/day in terms of remission rate, total adverse events or withdrawals due to adverse events. No patient experienced serious adverse events in both treatment groups. Mortality, hospitalization and quality of life were not reported.

References

1. Prantera et al. A new oral delivery system for 5-ASA: preliminary clinical findings for MMx. Inflamm Bowel Dis 2005; 11: 421-427.
2. Sutherland L et al. Oral 5 aminosalicylic acid for induction of remission in ulcerative colitis. Cochrane database of systematic reviews 2006, Issue 2. Art No.: CD000543. DOI:10.1002/14651858.CD000543.pub2.
3. Shire BioChem Inc. Mezavant Product monograph.
4. Kamm MA et al. Once daily, high-concentration MMX mesalamine in active ulcerative colitis. Gastroenterology 2007; 132: 66-75.
5. Lichtenstein GR et al. Effect of once or twice daily MMx mesalamine (SPD476) for the induction of remission of mild to moderately active ulcerative colitis. Clin Gastroenterol and Hepatol 2007; 5: 95-102.