P0629Distinct fatigue trajectories in active IBD: clinical predictors and treatment-linked improvements independent of inflammation

Abstract Background Fatigue is one of the most debilitating and persistent symptoms in inflammatory bowel disease (IBD), often remaining despite adequate control of intestinal inflammation. Current treatments insufficiently address this burden, underscoring the need to better characterise its course and determinants 1. The study aimed to identify distinct fatigue trajectories in patients with active IBD, and to determine clinical and psychological predictors of fatigue improvement over one year. Methods Data were derived from a large prospective cohort within the 3TR consortium, including 207 patients with active endoscopic ulcerative colitis (UC) or Crohn’s disease (CD), recruited at 2 large referral centres. Assessments were performed at baseline, week 6 and 1 year after treatment initiation. Fatigue (FACIT-F), mental health (SF-36, mental component summary) and inflammatory markers (faecal calprotectin FC and C-reactive protein CRP) were collected at each visit. Latent class growth analysis (LCGA) was used to identify fatigue trajectory clusters based on intercepts and slopes of individual patients. Mixed-effects models tested the influence of advanced IBD treatment, baseline inflammation and mental health on fatigue changes. Results LCGA identified three distinct trajectories differing in fatigue severity (p 0.001) at baseline with mild (FACIT-F = 45.4), moderate (FACIT-F = 28.6) and severe (FACIT-F = 11) fatigue, with the majority (72.9%) of patients with active IBD in our cohort experiencing moderate-to-severe levels that often persist up to 1 year. The quadratic slopes over time did not significantly differ between the groups (p 0.05), although patients with mild or moderate fatigue improved significantly, particularly in the first 6 weeks (p 0.01), whereas those with severe baseline fatigue showed minimal change (p = 0.51; Figure 2A) 2. Treatment with upadacitinib (p 0.001), infliximab (p 0.001) and vedolizumab (p 0.05) was associated with greater fatigue improvement, while risankizumab (p = 0.07) and ustekinumab (p = 0.15) was not, despite similar baseline levels of fatigue (Figure 2B). Baseline mental health problems predicted worse initial fatigue, but greater improvement over time (p 0.05; Figure 2C). Neither FC nor CRP at baseline were significantly associated with fatigue changes (p = 0.53). Conclusion LCGA identified three distinct fatigue trajectories, where the evolution appeared largely independent of baseline inflammatory activity. Improvement in fatigue was more strongly associated with specific advanced therapies and baseline mental health problems than baseline inflammatory markers. The differences between biologics classes are seen in a non-randomized setting and should lead to randomized controlled comparisons between interventions. References: 1. Borren NZ, van der Woude CJ, Ananthakrishnan AN. Fatigue in IBD: epidemiology, pathophysiology and management. Nat Rev Gastroenterol Hepatol. 2019;16(4):247-259. doi:10.1038/s41575-018-0091-9 2. Cella D, de la Loge C, Fofana F, et al. The Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) scale in patients with axial spondyloarthritis: psychometric properties and clinically meaningful thresholds for interpretation. J Patient Rep Outcomes. 2024;8(1):92. doi:10.1186/s41687-024-00769-x Conflict of interest: Mr. Rinckhout, Sybren: No conflict of interest Abts, Tuur: I declare no conflicts of interest regarding my work. Travel expenses for conference attendance were covered by Sandoz. Nasehi, Fatemeh: No conflicts Bourgery, Matthieu: No conflicts Van Oudenhove, Lukas: No conflicts of interest to be reported Vergaelen, Elfi: No conflicts of interest to be reported Ferrante, Marc: Research grants from AbbVie, EG Pharma, Celltrion, Janssen, Pfizer, Takeda and Viatris Consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, MRM Health, Merck Sharp and Dohme, Pfizer, Takeda and ThermoFisher Speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare and Viatris Guedelha Sabino, João: Speaker’s fees: Lilly, Pfizer, Abbvie, Ferring, Falk, Takeda, Janssen, Fresenius, and Galapagos. Consultancy fees: Takeda, Pfizer, Janssen, Ferring, Fresenius, Abbvie, Galapagos, Celltrion, Pharmacosmos, and Pharmanovia. Research support: Galapagos, Viatris, and Eurogenerics. JS is supported by a Senior Clinical researcher grant from the Research foundation – Flanders. Schreiber, Stefan Wolfgang: Personal Fees: AbbVie, Alfasigma, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Celltrion, Falk, Ferring, Fresenius Kabi, Galapagos, Gilead, IMAB, Janssen, Lilly, MSD, Mylan, Novartis, Pfizer, Protagonist, Provention Bio, Roche, Sandoz/Hexal, Shire, Takeda, Theravance Rosenstiel, Philip: stock ownership Gerion Van Den Houte, Maaike: No conflict of interest to disclose Tran, Florian: Grant: Sanofi/Regeneron Personal Fees: Speaker’s fees: Abbvie, Bristol-Myers-Squibb, Celltrion Healthcare, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, J & J, Sanofi, Takeda Consulting honoraria: AbbVie, J & J, Takeda Non-financial Support: Sanofi for statistical analysis Verstockt, Bram: Research support from AbbVie, Biora Therapeutics, Celltrion, Landos, Pfizer, Sanofi, Sossei Heptares/Nxera and Takeda. Speaker’s fees from Abbvie, Agomab, Alfasigma, Biogen, Bristol Myers Squibb, Celltrion, Eli Lily, Falk, Ferring, Galapagos, Materia Prima, Johnson and Johnson, Pfizer, Sandoz, Takeda, Tillots Pharma, Truvion and Viatris. Consultancy fees from Abbvie, Alfasigma, Alimentiv, Anaptys Bio, Applied Strategic, Astrazeneca, Atheneum, BenevolentAI, Biora Therapeutics, Boxer Capital, Bristol Myers Squibb, Domain Therapeutics, Eli Lily, Galapagos, Guidepont, Landos, Merck, Mirador Therapeutics, Mylan, Nxera, Inotrem, Ipsos, Johnson and Johnson, Pfizer, Sandoz, Sanofi, Santa Ana Bio, Sapphire Therapeutics, Sosei Heptares, Takeda, Tillots Pharma and Viatris. Stock options Vagustim and Thethis Pharma.