Fatigue is a burdensome, multidimensional, and multifactorial symptom that is associated with a wide array of chronic illnesses, specifically occurring in nearly 50% of patients with inflammatory bowel disease (IBD). Although common, given its subjective nature, physicians often under-recognize and undertreat this debilitating symptom. There are multiple etiologies that can contribute to fatigue in patients with IBD, including disease activity, anemia, medications, psychosomatic symptoms, and alterations to the gut-brain axis. The management of fatigue in IBD can be challenging, as it is often times multifaceted. In this review, we summarize the available tools for the diagnosis and measurement of fatigue, discuss etiologies, and make recommendations for their management. We identify knowledge gaps for the workup and treatment of fatigue and propose an algorithm to aid physicians in the evaluation and management of fatigue in this unique population. However, future research is needed to address several areas of knowledge deficits and improve the management of fatigue in IBD.

INTRODUCTION:We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD).METHODS:This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation.RESULTS:A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49–0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48–0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients.DISCUSSION:UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

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