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P300. Health related quality of life results through week 22 from the CERTIFI study, a multicenter, randomized, double-blind, placebo-controlled Phase2b study of ustekinumab in patients with moderately to severely active Crohn's disease

B. Feagan1, C. Gasink2, L.‑L. Gao3, M. Blank3, J. Johanns3, C. Guzzo3, C.‑F. Chiou3, W. Sandborn4, S.B. Hanauer5, S. Targan6, P. Rutgeerts7, S. Ghosh8, W. De Villiers9, R. Panaccione10, G. Greenberg11, S. Schreiber12, S. Lichtiger13, B. Sands14

1Robarts Research Insitute, London, Canada; 2Janssen Research & Development, a division of Pharmaceutical Research & Development, Inc., Malvern, United States; 3Janssen Research & Development, a division of Pharmaceutical Research & Development, Malvern, United States; 4University of California, San Diego, La Jolla, United States; 5University of Chicago Medical Center, Department of Medicine, Section of Gastroenterology, Chicago, United States; 6Cedars-Sinai Medical Center, Los Angeles, United States; 7University Hospital Gasthuisberg, Department of Gastroenterology, Leuven, Belgium; 8University of Calgary, Department of Gastroenterology, Calgary, Canada; 9University of Kentucky Medical Center, Lexington, United States; 10University of Calgary, Director, Inflammatory Bowel Disease Clinic, Calgary, Canada; 11Mount Sinai Hospital, Toronto, Canada; 12University Hospital of Schleswig-Holstein, Department of General Internal Medicine, Kiel, Germany; 13Mount Sinai Medical Center, New York, United States; 14Mount Sinai Medical Center, Annenberg Building, Floor 5, Room 207cc, New York, United States

Background: To examine the impact of ustekinumab (UST) on HRQoL in CD over the course of induction and maintenance, in the CERTIFI study.

Methods: Patients with a CDAI score ≥220 and ≤450 who had previously failed or been intolerant of ≥1TNF antagonists were randomized to IV PBO or UST (1, 3, or 6 mg/kg) at wk0. At wk8, patients who received IV UST induction and were either responders (≥100 CDAI decrease) or non-responders at wk6, were re-randomized separately to SC maintenance with 90 mg UST or PBO at wks8 and 16, and assessed for maintenance efficacy at wk22. The IBDQ, assessing 4 dimensions of bowel symptoms, emotional function, systemic symptoms, and social function, was administered at wks0 (baseline), 6 and 22. Mean change from baseline in IBDQ and in each dimension of IBDQ, and the proportion of patients achieving a minimal clinically important difference (MCID) (≥16 point improvement from baseline in IBDQ), were assessed at wk6 and wk22.

Results: Median age was 38yrs and 58.7% of patients were female (n = 526). In the induction phase, among the 500 patients analyzable for IBDQ, the combined patients randomized to IV UST had a baseline mean (SD) IBDQ score of 115.5 (28.64) vs 119.5 (26.69) for IV PBO. For the 1, 3, and 6 mg/kg IV UST doses, mean improvement from baseline in IBDQ at wk6 (19.9, 22.7, and 24.8, respectively) was statistically significant vs PBO (11.8) (p < 0.05). The proportion of patients with a MCID at wk6 was 33.1% on PBO vs 45.0% on IV UST 1 mg/kg (p = 0.057), 47.7% on 3 mg/kg (p = 0.018), and 54.7% among those randomized to 6 mg/kg (p < 0.001). Changes in IBDQ dimension scores from baseline to wk6 were each significantly improved in combined IV UST vs IV PBO patients (p < 0.05). Of the 145 responders to IV UST induction who were re-randomized in the maintenance phase, the mean (SD) IBDQ score at wk22 was 158.8 (38.58) among those who continued to receive SC UST vs 138.5 (39.71) of patients re-randomized to SC PBO (p < 0.001). The proportion of patients with a MCID was 68.1% (47/69) among those who continued to receive SC UST vs 44.9% (31/69) of patients re-randomized to SC PBO (p = 0.005). At wk22, mean IBDQ dimension scores in wk6 UST responders remained significantly higher with SC UST vs SC PBO maintenance (p < 0.05).

Conclusions: In moderate-to-severe CD patients who failed previous TNF antagonist(s), IV UST induction significantly improved HRQOL vs PBO. During maintenance with SC UST, significant improvement in HRQOL in responders to induction was maintained through wk22.