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

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. 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. 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). 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. 1. Sands, et al. Gastroenterology 2017; 153:77–86.

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