Time to initial resolution of rectal bleeding and high stool frequency in patients who achieved clinical and endoscopic remission after up to 8 weeks

STUDY 303: Long-term Safety Data on

Mesalamine for Patients with Ulcerative Colitis

Objectives

Study design Patient disposition Definitions Safety of 8-week acute extension Efficacy of 8-week acute extension Summary

Mesalamine 2.4 and 4.8 g/day Is Effective for the Induction of Remission

Lichtenstein et al.1 and Kamm et al.2 studies: Two double-blind,placebo-controlled, phase III studies evaluating the efficacy and tolerability of mesalamine

Both studies demonstrated mesalamine 2.4 g/day (given q.d. or 1.2 g b.i.d.) and 4.8 g/day (given q.d.) to be efficacious and well tolerated for the induction of remission in patients with active, mild-to-moderate ulcerative colitis

Adapted from: 1Lichtenstein et al. Clin Gastroenterol Hepatol 2007;5:95–102. 2Kamm et al. Gastroenterology 2007;132:66–75.

Mild(Score = 1)

Moderate(Score = 2)

Severe(Score = 3)

Rectal bleeding Streaks of blood Obvious blood Mostly blood

Stool frequency 1-2/day > normal 3-4/day > normal > 4/day > normal

Mucosal appearance ErythemaDecreased vascular patternMinimal granularityFriability *

Marked erythemaFriability *

GranularityAbsent vascular patternBleeding minimal traumaNo ulcerations

UlcerationSpontaneous bleeding

PGA(Physician’s Global Assessment)

Mild Moderate Severe

* Friability moved from Score of 1 to 2

Adapted from Kamm et al. Gastroenterology 2007;132:66–75.

Modified* UC-Disease Activity Index

End Point Definitions

Relapse: Withdrawal from the study due to a requirement for alternative treatment (including a dose increase or surgery) for an exacerbation of UC

Remission: Modified UC-DAI score 1, calculated as a score of 0 for rectal bleeding and for stool frequency, a combined Physician’s Global Assessment (PGA) and sigmoidoscopy score of 1, no mucosal friability, and a sigmoidoscopy score reduction of 1 point or more from baseline

Adapted from Kamm et al. 2008;57(7):893-902.

STUDY 303 Efficacy Results: 8-Week Acute Extension Phase

(n = 107) (n = 78) (n = 78) (n = 41)

Prior treatment

Up to 8 weeks’ active treatment

Up to 16 weeks’ active treatment

Num

ber o

f pat

ient

s (%

)

Adapted from Lichtenstein et al. Poster presented at ACG 2007.

*Week 0=First study visit of the acute extension phase

8-Week Acute Extension Phase:Sigmoidoscopy Scores

STUDY 303 Acute Extension Phase Conclusions1,2

Mesalamine 4.8 g/day (2.4 g dosed b.i.d.) was well-tolerated in the 8-week acute extension phase

Safety profile similar to that of the parent studies (Lichtenstein et al. and Kamm et al.)

Mesalamine 4.8 g/day for up to 4 months was well-tolerated

Approximately 60% of patients achieved remission, using stringent clinical and endoscopic criteria

Adapted from: 1Lichtenstein et al. Poster presented at APhA 2007.2 Lichtenstein et al. Poster presented at ACG 2007.