B0407 - Improvement in Fatigue With Mirikizumab Therapy Is Associated With Improvements in Patient-Reported Outcomes in Patients With Moderately-to-Severely Active Crohn’s Disease

Introduction: Fatigue is a debilitating, underrecognized, multifactorial symptom experienced by many patients (pts) with Crohn’s disease (CD). We reported previously that fatigue was significantly improved in pts with CD receiving Mirikizumab (miri) in the AMAG study. Here we assessed the association between changes in selected pt reported outcomes (PROs) and changes in fatigue during the AMAG study.

Methods: 191 pts with moderately to severely active CD were randomized 2:1:1:2 into 4 treatment arms (placebo, 200mg, 600mg, 1000mg miri); miri or placebo (PBO) was administered intravenously every 4 weeks at Week (W) 0, W4, W8. At W12 pts were switched from PBO to miri and re-randomized between miri doses based on response. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. Additional PROs included the Inflammatory Bowel Disease Questionnaire (IBDQ), the Short Form (SF-36) health survey physical and mental health components, Pts’ Global Rating of Severity (PGRS), and Abdominal Pain Numeric Rating Scale. Pearson’s correlation coefficients, 95% confidence intervals, and p-values were calculated. Cohen’s conventions were used to assess strength of correlations. Data were pooled for all treatment arms including placebo.

Results: Change in FACIT-F at W12 or W52 showed strong correlations with changes at the same timepoint in IBDQ total score, and IBDQ bowel symptoms, systemic symptoms, emotional function, and social function dimensions, as well as with the SF-36 Mental and Physical Component Scores. Moderate correlations were seen with changes in PGRS and abdominal pain; each of the listed correlations was statistically significant (Table). Similar results were seen for correlations for each of these PROs at W52 (Table).

Discussion: Improvement in fatigue during treatment for CD was correlated with some aspects of physical symptom improvement, including abdominal pain, but also correlated strongly with emotional, social, and mental well-being. Investigations of bidirectional effects of brain-gut interactions could clarify the relationship between subjective perception of well-being and physical symptom improvement in CD.