Abstract Background Risankizumab, a selective anti–IL-23 monoclonal antibody, is approved for the treatment of moderate-to-severe Crohn’s disease (CD). Although pivotal trials have demonstrated its clinical and endoscopic efficacy, real-world data integrating multiple monitoring tools remain limited. The Bowel Ultrasound Score of Severity (BUSS) is a validated, non-invasive composite index combining bowel wall thickness, Doppler signal, wall stratification, and inflammatory fat. This multicenter study from the Apulian Network for Inflammatory Bowel Disease (AN-IBD) provides preliminary real-world data on early clinical, biochemical, and intestinal ultrasound responses to risankizumab induction therapy. Methods Adult CD patients initiating risankizumab between September 2023 and March 2025 across 19 IBD centers were retrospectively included. The induction regimen consisted of 600 mg intravenously at weeks 0, 4, and 8. Patients completing the 12-week induction phase were analyzed. Clinical remission was defined as a Harvey–Bradshaw Index (HBI) 5 without corticosteroids, clinical response as an HBI reduction ≥3 and/or 5, and biochemical remission as CRP ≤5 mg/L. Intestinal inflammation was evaluated using the BUSS at baseline (T0) and week 12 (T1). The primary endpoint was steroid-free clinical remission; secondary endpoints included clinical, biochemical, and combined remission rates, and change in BUSS score. Results A total of 112 patients (mean age 45.4 years; 35.1% female; mean disease duration 14.5 years) completed induction. Steroid-free clinical remission was achieved in 47.3%, clinical response in 52.7%, and combined clinical and biochemical remission in 27.7%. Resolution of extraintestinal manifestations occurred in 78.2% of affected patients. Among 56 patients with paired IUS data, the mean BUSS score decreased significantly from 6.74 to 5.24 (Δ = –1.5; p 0.001), with a greater reduction in combined clinical–biochemical responders (Δ = –2.55 vs –1.56 in non-responders). Patients previously exposed to ≥ 3 biologics achieved a clinical response in 19.0%. Conclusion These preliminary multicenter real-world data demonstrate that risankizumab induces early clinical, biochemical, and ultrasound improvements in patients with Crohn’s disease, including those with extensive prior biologic exposure. The parallel decrease in BUSS and clinical indices supports the value of a multimodal monitoring approach combining clinical, biochemical, and imaging parameters to optimize early assessment of response to IL-23 blockade in real-life practice. Conflict of interest: Dr. Palmisano, Chiara Maria: No conflict of interest Contaldo, Antonella: No conflict of interest Dell’Aquila, Paola: No conflict of interest Ditonno, Ilaria: None Suriano, Valeria: No conflict of interest Marzo, Manuela: No conflict of interest Paiano, Primaldo Nicola: No conflict of interest Marra, Antonella: No conflict of interest Mastronardi, Mauro: none Guglielmi, Francesco William: No conflict of interest Mazzuoli, Silvia: No conflict of interest Bossa, Fabrizio: none Perri, Francesco: No conflict of interest Stasi, Elisa: None Facciorusso, Antonio: No conflict of interest Bringiotti, Roberto: I have no conflic Fanigliulo, Libera: No conflict of interest Panarese, Alba: Nill Albano, Francesca: No conflict of interest Pisani, Antonio: No conflict of interest Tursi, Antonio: None Hadad, Yusef: No conflict of interest Pranzo, Giuseppe Carlo: No conflict of interest Bucci, Antongiulio: No conflict of interest Sacco, Rodolfo Cosma Damiano: No conflict of interest De Tullio, Nicola: No conflict of interest Allegretta, Leonardo: No conflict of interest Principi, Maria Beatrice: No conflict of interest
Palmisano et al. (Thu,) studied this question.