Improvement in fatigue but not joint pain and stiffness in Inflammatory Bowel Disease patients treated with advanced therapies: Interim findings from IBD-RESPONSE

Abstract

Background: Many patients with IBD experience extraintestinal symptoms such as fatigue, joint pain and stiffness, which may affect quality of life and be overlooked in clinical practice. These extraintestinal symptoms remain poorly characterised, particularly in relation to therapeutic response. Method(s): IBD-RESPONSE is a UK-wide, multi-centre observational study investigating predictors of response to advanced therapies. Patient-reported outcome (PRO) measures were collected before treatment and at week 14, including PRO-2 (used to calculate clinical response/remission), PROMIS Fatigue (8a), and a modified Axial Spondyloarthritis Disease Activity Score (ASDAS) for joint pain and stiffness which incorporates a CRP value. The ASDAS was completed by patients irrespective of having a rheumatological diagnosis. In this interim analysis of 531 patients, changes in extraintestinal symptom burden between baseline and week 14 were assessed using Wilcoxon signed-rank tests. Result(s): Median (IQR) baseline PROMIS-8a fatigue T-score across the cohort was 62.3 (57.5-68.6), whilst a score of 50 represents the United States (US) general population mean 1]. Based on the modified ASDAS-CRP score, 57.5% of patients were classified as having high or very high joint pain and stiffness at baseline, whilst only 10.4% of these patients had a rheumatological diagnosis. Whilst there was a significant improvement in fatigue from baseline to week 14 in treatment non-responders (median change in PROMIS T-score IQR] =-2.05 -6.08-2]; p < 0.001), the largest changes were seen in responders (median IQR] =-4.6 -9.3 - 1.05], p < 0.001) and those in clinical remission (median IQR] =-5.6 -13.1 - 0]; p < 0.001). Improvements were observed in both CD and UC patients, however, fatigue remained above the US general population mean at week 14 for those classed as responders or in remission across both CD (median IQR] T-score = 57.5 49.2-65.3]) and UC (median IQR] T-score = 53.6 49.2-61.3]). In contrast, joint pain and stiffness showed no significant improvement amongst treatment non-responders (median change in ASDAS-CRP IQR] =-0.26 -0.82 - 0.51]; p = 0.48), responders (median IQR] =-0.14 -0.585 - 0.337], p = 0.51) or those in clinical remission (median IQR] =-0.5 -1.02 - 0.72], p = 0.49) and remained elevated even among participants without a rheumatological diagnosis. Conclusion(s): Advanced therapies in IBD reduce fatigue but do not fully restore it to population norms. Joint pain and stiffness are prevalent in IBD and persists despite clinical response to therapy. These findings highlight the need for comprehensive evaluation and management of extraintestinal symptoms alongside intestinal inflammation.