Poor Correlation Between Clinical Disease Activity and Mucosal Inflammation, and the Role of Psychological Comorbidity, in Inflammatory Bowel Disease

OBJECTIVES: There is a move toward patient-reported outcome measures as end points in clinical trials of novel therapies for inflammatory bowel disease (IBD). However, the association between patient-reported symptoms and mucosal inflammation, and the influence of psychological factors, remains unclear. We examined this in a secondary care population. METHODS: Validated patient-reported disease activity indices were used to define clinically active disease in a cohort of 356 patients with ulcerative colitis (UC) or Crohn's disease (CD). A fecal calprotectin >= 250 mu g/g was used to define active mucosal inflammation. The hospital anxiety and depression scale (HADS) and patient health questionnaire (PHQ)-15 were used to assess for anxiety, depression, or somatization, respectively. Logistic regression analysis was performed to determine the association between symptoms, mucosal inflammation, and psychological comorbidity. RESULTS: Clinical disease activity was associated with mucosal inflammation in UC (odds ratio (OR) 3.36; 95% confidence interval (CI) 1.34-8.47) but not in CD (OR 1.69; 95% CI 0.74-3.83). Depression in UC (OR 1.21 per 1-point increase in HADS; 95% CI 1.02-1.44) and somatization in UC (OR 1.17 per 1-point increase in PHQ-15; 95% CI 1.03-1.33) and CD (OR 1.31 per 1-point increase in PHQ-15; 95% CI 1.13-1.52) were associated with clinical disease activity. Overall, patient-reported symptoms yielded poor positive predictive values for mucosal inflammation in both CD and UC. CONCLUSIONS: Patient-reported symptoms and the Harvey-Bradshaw index were poor predictors of mucosal inflammation in CD. Psychological comorbidity was associated with gastrointestinal symptom-reporting. A shift in the focus of IBD management toward one addressing both psychological and physical well-being is required.