Fatigue in inflammatory bowel disease: Mechanisms, assessment, and management strategies

Abstract

Fatigue is among the most prevalent and disabling symptoms in inflammatory bowel disease (IBD), affecting a substantial proportion of patients during active disease and persisting in many despite clinical remission. It is multidimensional, spanning physical, cognitive, and emotional domains, and it is a major determinant of health-related quality of life, work disability, and healthcare use. Correlations with conventional markers of intestinal inflammation are typically modest, indicating important contributions from extraintestinal, neuroimmune, nutritional, endocrine, sleep-related, and psychological mechanisms. This article is a narrative review with a structured literature synthesis, rather than a formal scoping review. The core search covered MEDLINE/PubMed, Embase, and the Cochrane Library from January 2010 to October 31, 2024, with targeted citation updates added during revision for recently finalized publications. Compared with recent broad reviews, the present manuscript adds three specific elements: explicit differentiation of evidence derived from primary randomized trials, prespecified patient-reported outcome analyses, and
post hoc
fatigue analyses; an updated synthesis of fatigue data for newer advanced therapies, particularly IL-23 and JAK-pathway agents; and a pragmatic biopsychosocial assessment-and-management framework with specific discussion of Arabic-language patient-reported outcome implementation and Middle East/North Africa practice considerations. Available evidence supports a stepwise clinical approach: First assess inflammatory activity and disease control; then screen systematically for reversible contributors including iron deficiency, other micronutrient deficits, endocrine abnormalities, sleep disorders, pain, mood disturbance, sarcopenia, and deconditioning. Validated instruments such as the Inflammatory Bowel Disease-Fatigue (IBD-F) questionnaire and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale are useful for serial monitoring. A clinically meaningful FACIT-Fatigue improvement appears to be context-specific; across IBD studies, approximately 6–10 points have the strongest empirical support, while trial-specific thresholds should be reported as originally prespecified. Biologic and targeted synthetic therapies can improve fatigue, but fatigue has rarely been a primary endpoint in pivotal trials. Anti-tumor necrosis factor agents, vedolizumab, ustekinumab, JAK inhibitors, and IL-23 inhibitors have all shown beneficial effects on fatigue-related outcomes, although the evidentiary strength varies from primary trial data to exploratory
post hoc
analyses. Nonpharmacological strategies including intravenous iron when indicated, exercise and rehabilitation, optimization of sleep and pain, and cognitive-behavioral or mindfulness-based interventions remain essential. Fatigue should therefore be recognized as a core manifestation of IBD and incorporated into routine patient-reported outcome assessment and treat-to-target discussions.