OP03Early kinetics of transmural healing in patients with Crohn’s Disease treated with risankizumab: Results of the multicenter prospective SKYNETICS study

Abstract Background We aimed to evaluate, in real-life practice, the kinetics of clinical, biochemical, and transmural efficacy of risankizumab in patients with Crohn’s disease (CD). Methods In this academic multicenter prospective study, adult patients (≥18 years) with CD who initiated risankizumab in routine practice for symptomatic CD according to PRO-2 with objective evidence of inflammation on ultrasound were included. Patients started risankizumab at a dose of 600 mg IV at weeks 0, 4, and 8, followed by 360 mg every 8 weeks (from W12) via an on-body injector. Ultrasound examinations were performed at W0, W4, and W12 to assess the kinetics of transmural response. Patients were subsequently followed long-term. The primary endpoint was transmural response, defined as a 25% decrease in IBUS-SAS at W4 and W12. Alternative definitions of transmural remission using the BUSS score or the us-C-score were also evaluated at W4 and W12. Secondary endpoints included clinical response and clinical remission according to PRO-2 (W4, W8, W12), biochemical response (change in fecal calprotectin), and transmural remission (normalization of ultrasound) (W4 and W12). Secondary long-term outcomes included treatment survival without discontinuation, hospitalization, progression of bowel damage, and surgery. Results A total of 101 patients were included, with a mean age of 42.9 ± 15.0 years, 58% women, and 45.9% active smokers. Montreal classification was as follows for disease location (L1 = 41% / L2 = 11% / L3 = 48%), phenotype (B1 = 28.9% / B2 = 42.1% / B3 = 28.9%), and prior perianal CD (37%). Among them, 44.9% had previously required intestinal resection. While 28% of patients had prior exposure to one biologic, 32% and 40% were exposed to two and ≥ 3 advanced therapies, respectively. Clinical response and clinical remission were observed in 57.7% and 33.9% at W4, 70.1% and 33.3% at W8, and 79.2% and 38.0% of patients at W12, respectively. Median fecal calprotectin levels were 269, 192, 200, and 135 µg/g at W0, W4, W8, and W12, respectively. Transmural response rates were 27.3% at W4 and 28.5% at W12 according to IBUS-SAS, 9.1% at W4 and 14.3% at W12 according to BUSS, and 52.3% at W4 and 54.3% at W12 according to the us-C-score. Transmural remission was achieved in 8.5% of patients at W12. Segmental transmural response did not differ between ileal and colorectal segments regardless of the scoring system used. Predictive factors of response and long-term outcomes will be available for the congress. Conclusion In this prospective multicenter study including unselected patients with Crohn’s disease previously exposed to at least one anti-TNF, risankizumab achieved early clinical, biochemical, and transmural effectiveness, supporting its use in this clinical situation. Conflict of interest: Domas, Quentin: No conflict of interest Serrero, Melanie: No conflict of interest Mathieu, Kelly: No conflict of interest M’Baye, Diari: No conflict of interest Huet, Julie: No conflict of interest Ferrari, Tessa: No conflict of interest Yzet, Clara: No conflict of interest Guillo, Lucas: No conflict of interest Hupé, Marianne: No conflict of interest Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Pereira, Bruno: No conflict of interest Buisson, Anthony: Consulting fees from: Abbvie, AlfaSigma, Amgen, Arena, Biogen, Celltrion, CTMA, Ferring, Galapagos, Guty Care, Janssen, Hikma, Lilly, Mylan, Nexbiome, Pfizer, Roche, Takeda, Tillotts Lecture fees from: Abbvie, AlfaSigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Hikma, Janssen, Lilly, Mayoli-Spindler, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor-Pharma Research fundings from: Abbvie, AlfaSigma, Celltrion, Janssen, Lessaffre, Lilly, Pfizer, Takeda