A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 2b Study of Ustekinumab, a Human Monoclonal Antibody to Il-12/23p40, in Patients with Moderately to Severely Active Crohnʼs Disease: Results through Week 36 from the CERTIFI Trial: 2011 ACG Presidential Poster (2011)

Purpose: Ustekinumab (UST) safety and efficacy were evaluated in patients (pts) with moderate-to-severe CD previously failing anti-TNFs. Methods: UST was evaluated in moderate-to-severe CD pts failing anti-TNFs. Pts with CDAI score 220-450 were randomized to IV PBO or UST 1, 3, or 6mg/kg at wk0. Primary endpt was clinical response at wk6. At wk8, wk6 responders and nonresponders who received IV UST were separately re-randomized to SC 90mg UST or PBO maintenance at wks 8 & 16. During maintenance, steroid tapering was mandated and assessments were at wk22. Pts were followed until wk36. Results: Of 526 pts randomized, baseline mean CDAI was 324; 49.6% were on steroids (including budesonide); 48.8% failed >2 anti-TNFs and primary or secondary non-response or intolerance criteria were met by 30.4%, 72.2% & 33.5% of pts, respectively. At wk6, 39.7% in the 6mg/kg UST grp were in clinical response vs. 23.5% PBO (p=0.005). Results by dose (Table). All 3 doses had significant changes vs PBO at wk6 in CRP, IBDQ, mean CDAI, 70 pt drop, and lactoferrin/calprotectin. In maintenance, among pts in clinical response to UST at wk6, 41.7% (30/72) on UST were in remission at wk22 vs 27.4% (20/73) PBO (p=0.029); 69.4% vs 42.5% remained in clinical response (p<0.001) and 30.6% (22/72) on UST were in steroid-free remission at wk22 vs 17.8% (13/73) PBO (p=0.048). Among pts on systemic steroids at baseline(n=35 UST; 26 PBO), median dose was 20mg. At wk22, median dose [IQrange] was 5mg [0,15]on UST vs 10mg[2.5,20] PBO (p=NS), and 5mg [0,19] vs 15mg [2.5,20] at wk36 (p<0.05). Through 36wks, proportions of AEs, SAEs, and infections in the UST & PBO grps were similar during both induction and maintenance. The only malignancy was a basal cell skin Ca. There were no major adverse CV events, deaths, serious opportunistic infections or TB.TableConclusion: In moderate-to-severe CD pts previously failing anti-TNFs, UST induced and maintained clinical response. Signifantly greater proportion of wk6 responders achieved clinical remission and steroid-free remission at wk22 on SC UST vs SC PBO. IV and SC UST were well tolerated through wk36. Disclosure: BG Feagan: Investigator, Centocor Research and Development, Inc.; C Gasink: Employee, Centocor Research and Development, Inc.; L Gao: Employee, Centocor Research and Development; MA Blank: Employee, Centocor Research and Development; J Johanns: Employee, Centocor Research and Development; C Guzzo: Employee, Centocor Research and Development; B Sands: Investigator, Centocor Research and Development; S Hanauer: Investigator, Centocor Research and Development; S Targan: Investigator, Centocor Research and Development; P Rutgeerts: Investigator, Centocor Research and Development; S Ghosh: Investigator, Centocor Research and Development; W de Villiers: Investigator, Centocor Research and Development; R Panaccione: Investigator, Centocor Research and Development; G Greenberg: Investigator, Centocor Research and Development; S Schreiber: Investigator, Centocor Research and Development; S Lichtiger: Investigator, Centocor Research and Development; WJ Sandborn: Investigator, Centocor Research and Development. This research was supported by an industry grant from This study was sponsored by Centocor Research and Development, Inc.