S1035 Analysis of Baseline Characteristics Associated With Clinical Response to Ustekinumab IV Re-Induction Strategy in Patients With Crohn’s Disease in the POWER Trial

Introduction: The 36-week (W) POWER trial evaluated the efficacy and safety of a single intravenous (IV) re-induction ustekinumab (UST) dose vs continued UST subcutaneous (SC) treatment in Crohn’s disease (CD) patients with secondary loss of response (LoR) to standard UST maintenance therapy. Here, we report subgroup analysis of the primary endpoint by baseline characteristics. Methods: Adults with moderately–severely active CD who initially responded to UST IV induction therapy per label and later experienced LoR were included. LoR has been previously defined1. At baseline (W0), randomized patients received ∼6mg/kg IV UST/SC placebo (IV arm) or IV placebo/SC UST 90mg (SC arm), followed by SC UST 90mg dosing at W8/16. Descriptive statistics were used to summarize baseline characteristics. Clinical assessments occurred at W0/8/16. Primary endpoint: clinical response (CRes; decrease of ≥100 points from W0 in CD activity index [CDAI] or CDAI < 150) at W16. Odds ratios (ORs), confidence intervals (CIs) and P-values were estimated with a logistic regression model. Results: The full analysis set comprised 215 patients at W0 (SC, n=107; IV, n=108). At W16, 86.0% (SC) and 92.6% (IV) of patients completed treatment. At W16, 37.4% (SC) and 49.1% (IV) of patients achieved CRes (P=0.089). Of all baseline characteristics, disease location and duration, inflammatory biomarkers and prior biologic failures were of particular interest (Table 1). A greater proportion of patients from the IV vs SC arm achieved CRes at W16 (OR 3.6; 95%CI 1.6–8.1; P=0.002) of those with ileum and colon involvement. Patients with disease duration of < 5 years in the IV (n=22) vs SC (n=20) arm were more likely to achieve W16 CRes (OR 4.5; 95%CI 1.2–17.4; P=0.029). A greater proportion of patients in the IV vs SC arm with elevated baseline C-reactive protein (OR 2.1; 95%CI 1.1–4.0; P=0.029) or fecal calprotectin (OR 2.0; 95%CI 1.0–4.0; P=0.045) achieved W16 CRes as did patients with 1 prior biologic failure (OR 2.8; 95%CI 1.0–7.6; P=0.042). Conclusion: POWER assessed the efficacy and safety of UST IV re-induction in patients with LoR during UST maintenance therapy. This analysis suggests that patients with fewer prior biologic exposures and shorter disease duration but a higher disease burden at baseline including greater disease extent involving ileum and colon, or elevated inflammatory biomarkers, are more likely to benefit from UST IV re-induction therapy. 1. S.W. Schreiber, et al. J Crohns Colitis. 2023;17(Suppl 1):571 (Abstract P436). Table 1. - Proportion of patients who achieved clinical response*† at Week 16 by baseline characteristics (Full analysis set). As the primary endpoint was not met, all P-values should be considered nominal Baseline and clinical disease characteristics UST SC (n=107), n/N (%) UST IV (n=108), n/N (%) OR‡ (95%CI); P-value Age (median years) ≤40 22/62 (35.5) 28/52 (53.8) 2.1 (1.0; 4.4); P=0.060 >40 18/45 (40.0) 25/56 (44.6) 1.3 (0.6; 2.8); P=0.58 CDAI Score ≤300 24/68 (35.3) 30/68 (44.1) 1.4 (0.7; 2.9); P=0.312 >300 16/39 (41.0) 23/40 (57.5) 2.0 (0.8; 4.8); P=0.138 Prior CD-related surgery history Total or subtotal colectomy 4/9 (44.4) 7/17 (41.2) NE Partial bowel resection 12/28 (42.9) 21/39 (53.8) 1.5 (0.5; 4.0); P=0.472 Current draining fistula 2/10 (20.0) 4/11 (36.4) NE Prior perianal surgery 4/21 (19.0) 14/23 (60.9) 5.8 (1.5; 23.3); P=0.013 Involved gastrointestinal areas Ileum only 13/28 (46.4) 10/29 (34.5) 0.6 (0.2; 2.0); P=0.434 Colon only 11/22 (50.0) 10/24 (41.7) 0.7 (0.2; 2.3); P=0.505 Ileum and colon 16/55 (29.1) 33/55 (60.0) 3.6 (1.6; 8.1); P=0.002 Disease duration (years) < 5 5/20 (25.0) 13/22 (59.1) 4.5 (1.2; 17.4); P=0.029 ≥5 35/87 (40.2) 40/86 (46.5) 1.3 (0.7; 2.4); P=0.395 Prior failed biologics 0 1/8 (12.5) 5/12 (41.7) NE 1 15/37 (40.5) 21/33 (63.6) 2.8 (1.0; 7.6); P=0.042 2 13/35 (37.1) 18/35 (51.4) 2.0 (0.7; 5.3); P=0.173 3 10/25 (40.0) 6/23 (26.1) 0.6 (0.2, 2.0); P=0.363 4 1/2 (50.0) 3/5 (60.0) NE Baseline biomarker levels CRP ≤3 mg/L 12/32 (37.5) 10/29 (34.5) 0.9 (0.3; 2.5); P=0.780 CRP >3 mg/L 28/75 (37.3) 43/79 (54.4) 2.1 (1.1; 4.0); P=0.029 fCal ≤250 mg/kg 16/32 (50.0) 18/35 (51.4) 1.1 (0.4; 2.8); P=0.920 fCal >250 mg/kg 24/75 (32.0) 35/73 (47.9) 2.0 (1.0; 4.0); P=0.045 *Clinical response is defined as a decrease of ≥100 points from Week 0 or CDAI score of < 150 points.†Patients who had insufficient data at the designated analysis timepoint or a prohibited CD-related surgery, prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be caused by worsening CD prior to the designated analysis timepoint were not considered to have achieved clinical response, regardless of their CDAI score.‡OR, 95%CI for OR, and P-values were based on logistic regression.CDAI, Crohn’s Disease Activity Index; CI, confidence interval; CRP, C-reactive protein; fCal, fecal calprotectin; IV, intravenous; NE, not evaluated; OR, odds ratio; SC, subcutaneous; UST, ustekinumab.

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