Ustekinumab IV Induction Results in Crohnʼs Disease Symptom Improvement Within the First Week in Anti-TNF Refractory Patients: P-014

Introduction: In both the UNITI-1&2 Crohn's disease (CD) studies, a single 6mg/kg Ustekinumab (UST) IV infusion showed significantly greater rates of clinical response & remission vs placebo, and significant reductions in CDAI (and >70 pt reduction)1 by the first post-baseline visit at Wk 3.2 It remains to be determined how soon pts see benefit (ie. before Wk 3). Methods: Patient (pt) CDAI diary daily data (day -7 to +14) from the UNITI-1 study of pts who had previously failed TNF antagonists were compiled and analyzed post-hoc for the 3 pt-reported CDAI components (stool frequency[SF], abdominal pain[AP], & general well-being[WB]). Mean change in these daily scores with IV UST 6 mg/kg and 130mg were compared vs. placebo (PBO), as were 2-item SF+AP PRO2 weekly, over the 7d prior, weighted either 1:1 or as a CDAI subscore (assessed by mean change, and as % of pts with >50pt improvement). Ranked transformation was used to compare groups for all analyses. Results: IV UST induced significant improvement in all 3 components within the first 2 wks, with AP first significantly better than PBO on d2 for both UST doses, and consistently significantly better than PBO beginning on d6 for 6mg/kg and d8 for 130mg (Figure). Mean improvement in SF was first significantly better than PBO on d7 for UST both doses, while this occurred on d8 for WB. Week 1 and 2 SF+AP with CDAI weighting was significantly improved for both UST doses vs PBO at d7 and d14, & SF+AP added with equal 1:1 weight was significantly improved for both UST doses at d14 & for 130mg on d7(Table 1). 29.3% of 6mg/kg & 31.4% of 130 mg groups attained ≥50pt improvement in CDAI solely based on SF&AP components over the second week vs 18.8% in the PBO group (p < 0.05 and p < 0.01, respectively).FigureTable: Table. UNITI-1 Mean Change in Stool Freq and Abd Pain from CDAIConclusion: Even in the refractory CD population of previous anti-TNF failures in UNITI-1, symptom relief based on individual pt-reported CDAI components began to show significant improvement as early as 1 day post UST infusion, and was seen consistently among all 3 components by d8 with both IV UST doses, confirmed by consistent PRO2 benefit in the second week. These findings support previously reported significant early efficacy seen at the first post-baseline (Wk3) visit in the UNITI induction studies.2.