P281 Combined clinical and biological response (concomitant CRP and faecal calprotectin reductions) in induction and maintenance from the phase 3 ustekinumab Crohn's disease studies. (16th January 2018)

• Record Type: Journal Article
• Authors: Colombel, J -F; Gasink, C; Oortwijn, A; van Kruchten, R; Sloan, S; Laliman, V; Rutgeerts, P; Ghosh, S; Sandborn, W; Feagan, B; Sands, B
• Is Part Of: Journal of Crohn's and colitis. Volume 12:Number 1(2018:Jan.)Supplement 1
• Page Start: S243
• Page End: S243
• Publication Date: 2018-01-16
• Subjects: Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjx180.408
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background: Ustekinumab(UST) has been shown to induce and maintain clinical response and remission in Crohn's disease (CD) in two induction [(UNITI-1 (anti-TNF failures) and UNITI-2 (conventional therapy failures)] and 1 maintenance (IM-UNITI) randomised, PBO-controlled Phase 3 trials. The use of a more stringent composite outcome of clinical response and a ≥50% reduction from baseline(BL) in either fecal calprotectin(FeCa) or CRP concentration has been shown to decrease PBO rate and facilitate assessment of meaningful treatment effect. 1 This post-hoc analysis describes the rates of achievement of this composite outcome with UST/PBO IV induction and SC maintenance. Methods: In the UNITI trials, patients received PBO, UST 130 mg or ~6 mg/kg IV and were evaluated after 6 weeks. UST IV responders at week 8 were re-randomised to PBO, UST 90 mg q8w or 90 mg q12w during maintenance. Patients with elevated CRP or FeCa at BL and evaluable measurement to assess a 50% change at week 6 were included in this analysis ( n = 613 UNITI 1; n = 539 UNITI 2; n = 351 IM-UNITI). Rates of clinical response (CDAI decrease from BL ≥100 points or CDAI<150) and clinical remission (CDAI<150) associated with ≥50% reduction from BL in CRP or FeCa at wk6 and wk44 were determined per treatment arm. Results: Clinical and biological response(CBR) at wk6 was achieved in a significant higher proportion of patients on UST 130 or 6mg/kg vs. PBO respectively 21.3% and 20.8% vs. 8.4% in UNITI 1; p < 0.0001 and 32.2% and 37.6% vs. 12.8% in UNITI 2; p < 0.0001. A similar pattern was observed for clinical remission and biological response(Table). Among all randomised patients in IM-UNITI with an elevated FeCa or CRP at induction BL, a significantly higher proportion of UST patients achieved CBR outcomes vs. PBO(Table). Among patients in clinical response to PBO, UST q12w and UST q8w respectively 21/49 (42.9%), 44/63 (69.8%), and 45/62 (72.6%) also had biologic response. The use of the composite endpoint reduced PBO rates and heightened differences between UST arms and PBO (Figure). Conclusions: Clinical and biological response rate was significantly greater for patients receiving UST vs. PBO(IV induction and SC maintenance) in both anti-TNF and conventional therapy failure CD populations. Biologic response was observed in approximately 70% of responders to SC UST maintenance therapy. The use of a composite endpoint reduced PBO rates and heightened differences between UST and PBO arms in the maintenance trial. Reference: 1. Sands, et al . Gastroenterology 2017; 153:77–86.