B0408 - Improvement in Fatigue With Mirikizumab Therapy Is Associated With Clinical Remission and Pain Improvements but Not With Endoscopic Response in Patients With Moderately-to-Severely Active Crohn’s Disease

Introduction: Fatigue is common in patients (pts) with Crohn’s disease (CD) and negatively impacts quality of life. We previously reported that fatigue improved in pts with CD receiving mirikizumab (miri) in the AMAG study in all treatment arms. The association between changes in clinical and inflammatory markers and changes in fatigue might reveal the mechanism of fatigue relief.

Methods: 191 moderately-to-severely active CD pts were randomized 2:1:1:2 into 4 treatment arms (placebo [PBO], 200mg, 600mg, 1000mg miri), administered intravenously every 4 weeks at Weeks (W) 0, 4, 8. At W12 pts were switched from PBO to miri and rerandomized between miri doses based on response. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. Endoscopic response was defined as ≥50% reduction from baseline in total Simplified Endoscopic Activity Score for Crohn’s Disease. For continuous variables, Pearson’s correlation coefficients, 95% confidence intervals, and p-values were calculated. Cohen’s conventions were used to assess strength of correlations. Analysis of covariance was used to assess relationship between change in FACIT-F and endoscopic response at the same timepoint adjusting for baseline FACIT-F values. Data were pooled for all treatment arms including PBO.

Results: Mean change in FACIT-F scores for pts with and without endoscopic response at W12 were 8.1 and 7.2, respectively (p=0.33) and at W52 were 13.9 and 13.7, respectively (p=0.54). At W12, change in FACIT-F showed moderate but statistically significant correlation with change at the same timepoint in Crohn’s Disease Activity Index (CDAI) total score, abdominal pain, and stool frequency. Weak but statistically significant correlations were observed with calprotectin, and C-reactive protein (Table). At W52, change in FACIT-F was moderately but significantly correlated with change in CDAI total score, abdominal pain, and stool frequency (Table).

Discussion: Considering the limitation of the posthoc analysis and design of this Phase 2 trial, improvements in fatigue were significantly associated with improvement in CDAI score, abdominal pain, and stool frequency in patients with CD. Although fatigue has been hypothesized to be mediated in part by inflammatory cytokines, our data showed no consistent relationship of improvement in fatigue with changes in objective markers of disease activity, suggesting the possibility of alternative or additional mechanistic processes for fatigue in CD.