DOP032Comparative study on the effectiveness, durability, and safety of upadacitinib versus risankizumab after anti-TNF failure in Crohn’s Disease: The U-PARIS study of ENEIDA

Abstract Background Upadacitinib (UPA) and risankizumab (RSK) are alternatives for Crohn’s disease (CD) patients refractory to conventional therapies or biologics, although their optimal positioning is unclear. Aims to compare the durability and effectiveness of UPA and RSK after biologic failure in CD; to identify risk factors for relapse and for therapy discontinuation; and to explore safety profile of UPA and RSK in this scenario. Methods Adult patients from the prospectively-maintained ENEIDA registry of GETECCU who received UPA or RSK as second- (after 1 anti-TNF) or third-line (after 2 anti-TNFs, after 1 anti-TNF+vedolizumab, or after 1 anti-TNF+ustekinumab) with ≥12 weeks of follow-up, were included. Clinical remission was defined as Harvey-Bradshaw Index (HBI) ≤ 4, and clinical response as a decrease in HBI 3 points. Biologic remission was considered as faecal calprotectin (FC) ≤ 250 µg/g, and biologic response as a reduction of ≥ 50% in FC levels. Endoscopic activity was graded as quiescent (remission), mild, moderate or severe (as endoscopist’s criteria); and radiologic activity as absence/presence according to radiologist. Outcomes were evaluated at 12, 24, and 48 weeks. Treatment durability was analysed using Kaplan-Meier curves, and factors for therapy discontinuation and relapse were identified by Cox regression. All adverse events (AEs) were recorded. Results A total of 562 patients from 39 centers were included UPA: n = 242 (43%), RSK: n = 320 (57%) (Table 1). In second-line, 12 and 24-week durability was 70%/59% for UPA and 72%/72% for RSK; in third-line, 61%/40% for UPA, and 80%/76% for RSK (p 0.05). Outcomes were included in Table 2. In second-line, predictive factors for therapy discontinuation were stricturing-fistulising behaviour (Hazard Ratio HR=1.9, 95% confidence interval CI=1.1-3.3), and UPA vs. RSK treatment (HR = 1.8, 95%CI=1.1-3.1). In third-line, UPA treatment was associated with treatment discontinuation (HR = 2.4, 95%CI=1.5-4). The severity of CD at baseline was associated with relapse in second- (HR = 7.1, 95%CI=3.9-12.7) and in third-line (HR = 5.4, 95%CI=3.4-8.7). AEs were reported in 64 (28%) UPA- and 28 (10%) RSK- treated patients (p 0.05), most commonly acne for UPA, while infections predominated with RSK. Treatment was maintained in 81% of UPA and 91% of RSK patients with AEs (p 0.05). Conclusion UPA and RSK are effective options after biologic failure in CD patients. Both agents showed high treatment durability with greater persistence observed for RSK in third-line. CD behaviour and UPA treatment (vs. RSK) were predictive factors for therapy discontinuation, while severity of CD at baseline predicted relapse. AEs occurred more frequently with UPA, leading to a higher rate of treatment discontinuation compared with RSK. References: * P. Nos, M. Barreiro-de Acosta and F. Bermejo share senior authorship. Conflict of interest: Rubín De Célix, Cristina: Cristina Rubín de Célix has received education funding from Ferring, Tillotts Pharma, AbbVie, Sandoz, Alfasigma, Lilly, Norgine, MSD, Pfizer, Takeda, and Janssen Granja, Alicia: No conflict of interest Iborra, Marisa: No conflict of interest Garcia Alonso, Francisco Javier: I have acted as a speaker for Abbvie, Lilly and Johnson and Johnson Vela, Milagros: No conflict of interest de Castro, Luisa: No conflict of interest García-Sola, Claudia: No conflict of interest Barrero, Sara: I have no conflicts of interest to declare. Varela Trastoy, Pilar: No conflict of interest Robledo Andrés, Pilar: No conflict of interest Riestra, Sabino: No conflict of interest Ponferrada Diaz, Angel: financial support for travelling and educational activities from Johnsson and Johnsson, AbbVie, Takeda, Alfasigma, Lilly, Faes Farma and Ferring. Ceballos Santos, Daniel: None Camps, Blau: No conflict of interest Gisbert, Javier: Grant: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Personal Fees: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Other: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. García, María José: Other: MJ García has received financial support for travelling and educational activities from Janssen, Pfizer, Abbvie, Takeda and Ferring. Diz-Lois Palomares, Mª Teresa: No conflict of interest Moralejo Lozano, Óscar: I have received educational funding from Abbvie, Johnson & Johnson, Takeda, Kern Pharma, Alfasigma, Pfizer, Lilly, Sandoz, Dr. Falk Pharma, Ferring, and Tillotts. I have also served as a speaker for Abbvie, Takeda, Alfasigma, and Lilly. Rafael de La Cruz, David: No conflict of interest López, Eider: No conflict of interest Martinez Pascual, Cristina: No conflict of interest Izquierdo, Sandra: None. Iglesias Flores, Eva: has served as a speaker, consultant and advisory member for or has received research funding from AbbVie, Janssen, Takeda, Gillead, Celgene, Pfizer, Lilly, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, and Adacyte, Ferreiro Iglesias, Rocio: RF-I has served as a speaker, or has received research or education funding from AbbVie, Takeda, MSD, Pfizer, Janssen, Adacyte, Ferring, Casen Recordati, Palex, Tillotts Pharma, Dr. Falk, Chiesi, Faes Farma, Alphasigma. Argüelles-Arias, Federico: No conflict of interest Martin, Daniel: I have served as speaker for and received consulting fees from Abbvie, Takeda, Jansen, Ferring, Tillots, Dr. Falk Pharma, Faes Pharma an Persan Ruiz Ramírez, María Ángeles: No conflict of interest Vega Villaamil, Pablo: None Trapero Martinez, Ana María: No conflict of interest Roig Ramos, Cristina: CR has received support for conference attendance and education funding from Kern Pharma, Ferring, Alfasigma, Faes Farma, Pfizer and Takeda. Madero Velázquez, Lucía: None Mañosa Ciria, Miriam: Personal Fees: Abbvie, FAES Pharma, Ferring, Jannsen, MSD, Pfizer, Tillots and Lilly Brunet, Eduard: I have served as a speaker and consultant for Janssen and Chiesi, Kern, Takeda and Alfasigma. Zabana, Yamile: Personal Fees: AbbVie, Adacyte Therapeutics, Alfa-Sigma, Amgen, Boehringer Ingelheim, Dr Falk Pharma, FAES Pharma, Fresenius Kabi, Ferring, Galapagos, Janssen-J & J, Kern Pharma, Lilly, MSD, Pfizer, Sanofi, Sandoz, Takeda, Tillots Pharma Non-financial Support: Shire, Otsuka, Almirall Pajares Villarroya, Ramón: No conflict of interest Altadill, Ariadna: No conflict of interest Domènech Moral, Eugeni: Personal Fees: I have served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Gilead, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, Tillots. Other: I have served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Alfasigma/Galapagos Biogen, Celltrion, Ferring, Gilead, GoodGut, Imidomics, Janssen, Kern Pharma, Lilly, MSD, Pfizer, Roche, Takeda, Tillot