Abstract Background Risankizumab is an established treatment for Crohn’s Disease (CD). Recent data suggest that intensifying therapy may benefit patients with inadequate responses. This study aimed to evaluate the safety and effectiveness of Risankizumab reinduction or intensification in patients with CD. Methods A multicenter retrospective observational study was conducted at 8 hospitals. Consecutive adult patients with CD with at least one intravenous reinduction dose or at least two intensified doses every 4 or 6 weeks were eligible. Patients with ulcerative colitis, dual combination therapy or 14 weeks follow-up were excluded. The primary outcome was the rate of steroid-free clinical remission (SFCR) and fecal calprotectin normalisation (250) at 3 months. Clinical and biochemical assessments were conducted at baseline, as well as at 3-4 months and 6 months. Continuous variables were compared using the Wilcoxon test, while persistence was assessed using the Kaplan-Meier method. Results A total of 74 patients were included, 40 males (54.1%) with a median age of 53.5 years (IQR 44-64). The median number of previous advanced therapies was 3 (IQR2-4), with 39 patients (52.7%) with more ≥ 3 therapies. After a median of 6 months (IQR 3.2-8.9) after Risankizumab initiation, 60 patients underwent dose intensification (81.1%), 10 patients reinduction and in 4 patients, both reinduction and intensification were performed. The median IHB decreased from 6 (IQR 5-7) to 4 (IQR 2-6) at 3 months (p = 0.001) and remained at 4 (IQR 2-6) at 6 months (p = 0.001). Fecal calprotectin decreased from 724 (371-1503) to 539 (191-1236) at 3 months (p = 0.13) and to 574.5 (IQR 290-1200) at 6 months (p = 0.001). At 3 months, 10 patients (13.5%; 95 CI 6.7-23.5) achieved SFCR with fecal calprotectin normalisation, while SFCR was achieved in 50 patients (67.6%) and SF clinical response in 68 patients (91.9%; 95% CI 83.2-96.7%). After a median follow-up of 24.1 weeks (IQR 16.6-37.1), 14 patients discontinued Risankizumab (10 patients with non-response, 3 secondary loss of response and 1 adverse events) and 8 patients (10.8%) required surgery. At 6 months after intensification, the risk for Risankizumab discontinuation was 15.1% (95% CI 7.8-28.2) (figure 1). Adverse events were detected in 4 patients (5.4%; 2 infections, 1 cutaneous rash and 1 facial paralysis). Conclusion In this selected patient group, treatment intensification and reinduction were deemed safe, successfully recapturing 67.7% of patients in the short term. Nevertheless, the rate of combined clinical and biochemical remission was low. Larger prospective studies are needed to validate these findings and identify patients who may benefit from dosage adjustments after insufficient response. Conflict of interest: Fuentes-Valenzuela, Esteban: Esteban Fuentes-Valenzuela has received education funding from AbbVie, Alfa Sigma Pfizer, Takeda, DrFalk Pharma, Kern Pharma and Janssen and served as speaker for Janssen Lillo, Jorge: No conflict of interest Caballero Mateos, Antonio M: has received fees for lectures, consultancy work, or research support from: Lilly, Abbvie, Johnson & Johnson, Takeda, Pfizer, Alfasigma, Ferring, Farmasierra, Kern. Fuentes Coronel, Ana: No conflict of interest Alcaide Suárez, Noelia: No conflicts Lopez Martin, Maria Del Carmen: No conflict of interest Rascarachi, Gabriela: No conflict of interest Suarez Ferrer, Cristina Julia: No conflict of interest Fradejas Salazar, Paola Maria: No conflict of interest Santos Fernández, Javier: No conflict of interest Velayos, Benito: No Sicilia Aladren, Beatriz: Dra. B. Sicilia has received support for conference attendance, speaker fees, research support and consulting fees of Abbvie, FAES, Chiesi, Dr. Falk, MSD, Tillots Pharma, Khern Pharma, Janssen, Pfizer, Takeda and Lilly. Chivato Martín Falquina, Irene: I have received financial support from AbbVie, Kern, Takeda, and Janssen for postgraduate courses and attendance at scientific conferences. Gil Santana, Marina: No conflict of interest Calvache Rodriguez, Almudena: No conflict of interest Somoza Fernández, Beatriz: No conflict of interest Garcia Alonso, Francisco Javier: I have acted as a speaker for Abbvie, Lilly and Johnson and Johnson Bejerano Domínguez, Alicia: No conflict of interest Barrio Andres, Jesus: Jesús Barrio has served as a speaker, as consultant or has received research or education funding Abbvie, Takeda,Kern Pharma and Ferring.
Fuentes-Valenzuela et al. (Thu,) studied this question.