P0909Comprehensive disease control in vedolizumab treated patients with Crohn’s disease: post-hoc analysis of LOVE-CD

Abstract Background Crohn’s Disease (CD) and ulcerative colitis (UC) are often associated with high disease burden.1 STRIDE-2 consensus recommends a treat-to-target strategy, aiming for short-term symptom control and sustained remission for preventing long-term complications, hospitalizations and surgery. 2 While combined clinical, endoscopic and histological remission is associated with improved outcomes in UC, evidence for such so-called comprehensive endpoints in CD remains limited.3,4 This study aimed to evaluate comprehensive disease control in CD patients. Methods This analysis used data from the LOVE-CD study, which evaluated vedolizumab treatment in patients with early (disease duration 24 months) versus late CD (disease duration 24 months and prior anti-TNF exposure). Here we studied comprehensive disease control (CDC) at week 26 and 52, which was defined as corticosteroid-free clinical remission (CDAI ≤150), endoscopic remission (SES-CD ≤3), histological remission (RHI ≤3) and normal quality-of-life (IBDQ ≥170). Only patients with complete data at all timepoints were included. The relative contribution of clinical, endoscopic and histological remission and quality-of-life was assessed using McNemar’s test for paired categorical data. Results In total, 260 patients were included in LOVE-CD, of which 86 had early and 174 late CD. At baseline, clinical and endoscopic parameters were comparable among both groups (CDAI 255 vs. 259 and SES-CD 9 vs. 12, respectively). Complete data for CDC was available for 161 and 164 patients at week 26 and week 52, respectively. At week 26, CDC was achieved in 14/62 (22.6%) per-protocol (PP) early CD patients versus 8/99 (8.1%) late CD (Δ14.5%, p = 0.009). In the intention-to-treat (ITT) analysis, CDC was achieved in 14/86 (16%) early versus 8/174 (4.6%) late CD patients. At week 52, CDC rates were 25/66 (37.9%) in PP early CD compared with 16/98 (16.3%) in late CD (Δ21.6%, p = 0.002), while in the ITT analysis, CDC rates were 25/86 (29%) in early versus 16/174 (9.2%) in late CD. The most important factors contributing to CDC at week 26 and 52 were histological and endoscopic remission and quality-of-life, whereas clinical remission did not significantly affect CDC (p = 0.250) (table 1). Conclusion Patients with early CD receiving vedolizumab treatment achieved significantly higher rates of complete disease control up to week 52, compared to late CD. Endoscopic and histological remission were the most important factors, while normalization of quality of life, also played a pivotal role. These findings underscore the importance of early treatment and support CDC as a comprehensive treatment target in CD. When multiple ambitious endpoints are combined, only a minority of patients reach complete disease control. References: 1. Perler, B.K., et al. Presenting symptoms in inflammatory bowel disease: descriptive analysis of a community-based inception cohort. BMC Gastroenterol, 2019. 19(1): p. 47. 2. Turner, D., et al., STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology, 2021. 160(5): p. 1570–1583. 3. D’Amico, F., et al., Ulcerative colitis: Impact of early disease clearance on long-term outcomes - A multicenter cohort study. United European Gastroenterol J, 2022. 10(7): p. 775–782. 4. Danese, S., Evolving therapeutic goals in ulcerative colitis: towards disease clearance. Nat Rev Gastroenterol Hepatol, 2020. 17(1): p. 1–2. Conflict of interest: Mrs. Oldenburg, Lotte: No conflict of interest Baert, Filip J.: Grant: AbbVie, Amgen, EG, J & J, Takeda. Personal Fees: AbbVie, Abivax, Alpha Sigma, Arena, BMS,,Celltrion, Eli Lilly, Falk, Ferring, Fresenius, Galapagos, J & J, Pfizer, Sandoz, Takeda, Vifor. Bossuyt, Peter: Grant support for research from AbbVie, EG Consulting fee from AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Jeito capital, Lilly, Pentax, Pfizer, PSI-CRO, Roche, Takeda, Tetrameros Speakers fee from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, Springer Media Hoentjen, Frank: Frank Hoentjen has served on advisory boards or as speaker for Abbvie, CCRN, Janssen, Takeda, Pfizer, Celltrion, Teva, Amgen and Pendopharm, and has received independent research funding from Celltrion, Janssen, Abbvie, and Takeda. Clasquin, Esme: No conflict of interest Molnár, Tamás: Conflict of interest: Tamás Molnár has received speaker’s honoraria from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer, Janssen, Sandoz, Phytotec, Roche, Fresenius, Teva, Celltrion, Stada, BMS, Ferring, EwoPharma and SOBI Löwenberg, Mark: No conflict of interest Vermeire, Séverine: Grant: AbbVie, Pfizer, Takeda, J&J, Galapagos Personal Fees: AbbVie - AbolerIS Pharma - AgomAb - Alimentiv - Arena Pharmaceuticals - AstraZeneca - Avaxia- BMS - Boehringer Ingelheim - Celgene - CVasThera - Dr Falk Pharma - Ferring - Galapagos - Genentech-Roche - Gilead - GSK - Hospira - Imidomics - Janssen - J&J - Lilly - Materia Prima - MiroBio - Morphic - MrMHealth - Mundipharma - MSD - Pfizer - Prodigest - Progenity - Promakhos Therapeutics - Prometheus - Robarts Clinical Trials - Second Genome - Shire - Surrozen - Takeda - Theravance - Tillots Pharma AG - Zealand Pharma - Other: AbbVie, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer Inc, Galapagos, Mundipharma, D’Haens, Geert: Grant: Pfizer, BMS, Johnson and Johnson, Abbvie, Alimentiv BV, Eli Lilly, Takeda, Prometheus Laboratories Personal Fees: Abbvie, Abivax, Agomab, Alimentiv, Anaptys Bio, AstraZeneca, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Glaxo Smith Kline, Dr Falk Pharma, Pfizer, Johnson and Johnson, Merck, Mirador, Polpharma, Procise Diagnostics, Prometheus Biosciences, Sorriso Pharma, Spyre, Takeda, Ventyx