T1134 Relationship of C-Reactive Protein with Clinical Response Following Therapy with Monoclonal Antibody to IL-12/23p40 (Ustekinumab) in Crohn's Disease

Abstract

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 mg/L) leads to larger treatment effects with ustekinumab than lower baseline CRP levels, especially in IFXexperienced patients. Clinical response at Week 8 by baseline CRP levels