P0814Effect of IL-23 inhibitors on extra-intestinal manifestations and concurrent immune-mediated inflammatory diseases in patients with inflammatory bowel disease

Abstract Background Immune-mediated inflammatory diseases (IMIDs) and extra-intestinal manifestations (EIMs) are frequent in IBD and contribute substantially to morbidity. In recent years, IL-23 inhibitors have shown efficacy in IBD and in dermatological IMIDs such as psoriasis, while their benefit in rheumatological manifestations, particularly axial spondyloarthritis (SpA), appears limited. Real-world data on the effect of IL-23 inhibitors are therefore needed to guide their optimal positioning within IBD management. Methods This multicentric retrospective cohort included adult patients with ulcerative colitis (UC) or Crohn’s disease (CD) who initiated an IL-23 inhibitor (risankizumab, mirikizumab or guselkumab) for IBD and had at least one EIM or IMID at baseline. IBD and EIM/IMID activity were assessed after induction (week 6–14), at month 6 and at month 12 using physician’s global assessment. IBD outcomes included clinical, biochemical and endoscopic remission. Treatment discontinuation due to primary non-response (PNR), loss of response (LOR) or surgery was classified as non-remission. The primary endpoint was EIM/IMID response while secondary endpoints included steroid-free IBD remission and new-onset of EIMs/IMIDs. Results In total 83 patients were included (Table 1), with a median follow-up duration of 6 months (IQR 3-10). Steroid-free clinical remission was achieved in 23.9% post-induction and increased to 48% at 12 months (Figure 1). Psoriasis and hidradenitis suppurativa were active at baseline in 70% and 43% of patients, with response rates of 52% and 46% post-induction and 70% and 50% at 12 months respectively. At baseline, axial and peripheral SpA were active in 59% and 81% of cases respectively; response rates reached 47% and 58% post-induction and remained 43% and 50% at 12 months. In 4/22 patients (18.2%) a worsening of axial SpA was seen. Among 58 patients with available follow-up data, 4 (4.1%) developed new-onset EIMs or IMIDs. These included 2 cases of peripheral SpA and 1 case each of psoriasis and uveitis. In 9 patients (10.8%) treatment was discontinued after a median of 8 months (IQR 4.3-10.8). Multiple reasons for treatment discontinuation could be selected and included the following: worsening of the pre-existing EIM/IMID (n = 5), LOR (n = 3), PNR (n = 1) and new onset EIM/IMID (n = 1). Conclusion IL-23 inhibitors demonstrated effectiveness for IBD activity and psoriasis and achieved response rates of approximately 50% in hidradenitis suppurativa, axial and peripheral SpA. New-onset EIMs/IMIDs were uncommon. Interpretation of these outcomes remains limited due to small subgroup sizes, and further studies are needed to better define the role of IL-23 inhibition in IBD patients with coexisting IMIDs. Conflict of interest: Dr. Truyens, Marie: No conflict of interest Tolstoy, Xenia: No conflict of interest Calabrese, Giulio: Travel grant by Johnson and Johnson Speaker fee by Celltrion Balestrieri, Paola: Advisory board for Alfasigma- Janssen- Abbvie- Takeda- Eli Lilly Blesl, Andreas: Speaker fees from Abbvie, Aengus, Boston Scientific, Bristol-Myers Squibb, Dr. Falk Pharma, Genericon, Gilead, Janssen, Lilly, MSD, Olympus, Pfizer, PSI, Sandoz, Takeda, Vifor Pouillon, Lieven: Lieven Pouillon received advisory board fees from AbbVie, Alphasigma, Celltrion, Galápagos, Janssen-Cilag, Sandoz and Takeda consultancy fees from Ipsos NV and Ismar Healthcare funded by Viatris presentation fees from AbbVie, Alphasigma, Celltrion, Eli Lilly, Ferring, Galápagos and Pfizer and personal fees (congress support) from AbbVie, EG, Ferring, Galápagos, Janssen-Cilag, Norgine and Takeda. Shakweh, Eathar: No conflict of interest Filip, Rafal: No conflict of interest Todeschini, Alessia: The author has served as a consultant and/or received lecture fees from Abbvie, Alfasigma, Celltrion, Johnson & Johnson, Ely Lilly, Ferring, Lion Health,Takeda. Mocci, Giammarco: No conflict of interest Ribaldone, Davide Giuseppe: Davide Giuseppe Ribaldone declares the following paid consultancies, lecture fees for the past two years: Johnson & Johnson, Takeda, Celltrion, Alfasigma, Pfizer, Eli Lilly, Abbvie, Sandoz Jauregui-Amezaga, Aranzazu: I declare that I have no personal financial conflicts of interest related to my scientific activities. Any research funding received from Takeda, Johnson & Johnson, and AbbVie has been allocated to the research group to which I belong and has been used exclusively to support institutional or group-based research initiatives, with no personal financial benefit. Moraleja-Yudego, Irene: No conflict of interest Vieujean, Sophie: S Vieujean has received speaker’s fees from AbbVie, Alfasigma, Celltrion, Ferring, Johnson & Johnson, Eli Lilly, Takeda and declares consultancy/advisory fees from AbbVie. Taelman, Thibault: None García, María José: Other: MJ García has received financial support for travelling and educational activities from Janssen, Pfizer, Abbvie, Takeda and Ferring. Cremer, Anneline: Consulting fee from AbbVie, Takeda, Alfasigma, Johnson & Johnson. Speakers fee from AbbVie, Takeda, Alfasigma, Johnson & Johnson, Celltrion, Galapagos, Eli Lilly, Pfizer Savarino, Edoardo Vincenzo: Personal Fees: Takeda, Abbvie, MSD, Janssen, Sofar Felice, Carla: Advisory board for AbbVie, MSD, J & J. Vladimirova, Nora: grants from MSD, Novartis (paid to the employer) Attauabi, Mohamed: Research grants from Novo Nordisk Fonden and Lundbeck Foundation. Personal fees from Eli Lilly, Celltrion, and Lundcbeck foundation, outside the submitted work. Barreiro-de Acosta, Manuel: MBA has been speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Alphasigma, Lilly, Pfizer, Sandoz, Biocon, Abivax, Fresenius, Faes Farma, Ferring, Tillots, Chiesi, Adacyte, Diasorin, Oncostellae and SunRock. Peeters, Harald: Disclosures – conflicts of interest Financial support for research: Abbvie, Mylan, Amgen, Sandoz, Takeda Speaker fees: Janssen, Takeda, Abbvie Consultancy fees: Janssen, Fresenius-Kabi, Abbvie, Galapagos Innocenti, Tommaso: Speaker fees from Aurora Biofarma, and Ferring. Travel grants from Abbvie, Alfasigma, Celltrion, Eli Lilly, Ferring, Malesci, Pfizer. Holvoet, Tom: Speaker fees and/or researchs grant from abbvie, takeda, alfasigma, viatris, celltrion, J&J Gutiérrez Casbas, Ana: Consultant for: AbbVie, Amgen, Celltrion, Lilly, Ferring, Galapagos, Fresenius Kabi, J & J, Pfizer, Sandoz, Takeda.Speaker’s Fees for: AbbVie, Amgen, Bristol-Myers Squibb, Lilly, Ferring, Fresenius Kabi, Glaxo-Smith Kline, J & J, Pfizer, Roche, Sandoz, Shire, Takeda. Casanova, María José: María José Casanova, has received education funding from Pfizer, Takeda, Janssen, MSD, Dr. Falk, Shire, Ferring, Galápagos and Abbvie, and research funding from Lilly. Noor, Nurulamin: Grant: NMN reports grants from Celltrion, Dr Falk Pharma, Pfizer, Pharmacosmos, Tillotts. Personal Fees: NMN reports personal fees from AbbVie, BMS, Celltrion, Ferring, J & J, Lilly, Pharmacosmos, Takeda. Hedin, Charlotte Rose: Grant: C. R. H. Hedin has received specific project grants from Takeda and Tillotts. Personal Fees: C. R. H. Hedin served as a speaker and/or advisory board member for AstraZeneca, Abbvie, Dr Falk Pharma and the Falk Foundation, Galapagos, Janssen, Lilly, Pfizer, Ferring, Takeda, Tillotts Pharma, and received grant support from Tillotts and Takeda. These fees are invoiced by her employer. Nardone, Olga Maria: Advisory board fees from Eli Lilly, Nestlè, Janssen Speaker fees from AbbVie, Janssen, Eli Lilly, Ferring, Alfa Sigma, Recordati, Noòs, and Pfizer Lobatón Ortega, Triana: Grant: Abbvie, Ferring, Viatris, MSD, EG, Mundipharma, Biogen, Janssen, Pfizer, Takeda, Galapagos, Afasigma and Sandoz. Personal Fees: Speaker fees from MSD, Abbvie, Janssen, Amgen, Fresenius Kabi, Galapagos, Viatris, Ferring, Celltrion, Alfasigma, Lilly and Takeda. Consultancy fee from Janssen, Galapagos, Alfasigma, Amgen, Bristol Myers, Squibb Fresenius Kabi, Takeda and Abbvie