T1137 A Novel High Dose 1g Mesalamine Suppository (Salofalk®) Is As Efficacious As 500mg TID Suppositories in Mild to Moderate Active Ulcerative Proctitis: A Multicenter, Randomized Trial

Background:Short-term treatment with ustekinumab (CNTO 1275) has been studied in a Phase 2a study in patients with Crohn's Disease (CD) (CDAI ≥220-≤450 despite previous (or on-going conventional therapy) (N=104, primary population).Ustekinumab was well tolerated in the study.At week 8, 49.0% of patients receiving ustekinumab were in clinical response (CDAI reduction of ≥25% and ≥70 points) vs. 39.6% for placebo (p=0.34).In patients with prior infliximab (IFX) experience in the primary population (n=49), 59.1% receiving ustekinumab were in clinical response at week 8 vs. 25.9%receiving placebo (p= 0.02).The relationship between C-reactive protein (CRP), an acute-phase protein biomarker for inflammatory bowel disease activity, and clinical response to ustekinumab in this Phase 2a study is presented.Methods: Serum collected at week 0 and the pre-specified week 8 primary endpoint was analyzed for CRP using a high sensitivity assay (Quintiles, Smyrna, GA).Comparisons between the ustekinumab and placebo groups at week 8 were made using ANCOVA on the van der Waerden normal scores, adjusted for baseline CRP, for change in CRP from baseline, and Chi-square tests, for the proportion of patients in clinical response by CRP subgroup.Results: Median baseline CRP was 7.0 mg/L in both the primary and IFX-experienced populations.Median changes (mg/L) from baseline CRP at week 8 in the primary population were 0.00 and -1.8 following placebo (N=43) and ustekinumab (N= 46), respectively (p=0.074).In patients with prior IFX experience, the median change was +1.5 (placebo, N=23) and -3.8 (ustekinumab, N=20) (p=0.004).Within subgroups defined by baseline CRP using the central laboratory upper limit of normal of 6.0 mg/L, a similar treatment effect (based on clinical response) was observed.However, when analyzed by baseline CRP <10 or ≥10 mg/L, patients with CRP ≥10 not only demonstrated a lower placebo response rate, but also exhibited a higher rate of response to ustekinumab (Table ).This effect was most pronounced in IFX-experienced patients.Conclusion: The potential benefit of the IL-12/23p40 inhibitor, ustekinumab, in CD was supported by reductions in CRP.Although the sample sizes were small, there was also evidence suggesting that increased systemic inflammation as manifested by higher baseline CRP values (>10 mg/L) leads to larger treatment effects with ustekinumab than lower baseline CRP levels, especially in IFXexperienced patients.