Can Early Anti-TNF Treatment Modify the Outcome of Inflammatory Strictures?

Abstract

Background: Fatigue is a troubling problem for IBD patients and physicians alike. Recent population-based cohort studies by our group (Inflam Bowel Dis in press) and others have identified high levels of fatigue both when IBD is active (70-77%) and quiescent (30-36%). No previous studies have looked at fatigue over time in IBD. Methods: Data were obtained from Manitoba IBD Cohort Study participants (n=318; 51% Crohn's disease CD), a longitudinal population based study of persons diagnosed within 7 years of enrolment. Disease activity was measured every 6 months for 2 years to characterize long-term disease pattern as active, fluctuating or inactive, using the validated Manitoba IBD Index (Am J Gastro 2009). Fatigue (Multidimensional Fatigue Inventory), psychological functioning, and blood markers were assessed concurrently at baseline and 1 and 2 years later. Results: 31% had consistently inactive, 28% had fluctuating, and 42% had consistently active disease across the two years. Fatigue levels mapped approximately to disease patterns, with lowest average fatigue at each time point for those with consistently inactive disease (see table). A mixedeffects regression model with a random intercept showed that fatigue levels increased over time regardless of disease pattern (F=8.38,p=0.004). There was substantial individual variation in fatigue levels at baseline (intraclass correlation ICC=0.44), with minimal individualspecific variation in the rate of change over time. A disease pattern x subtype interaction (p=0.01) suggested that UC participants with consistently inactive disease had modestly higher fatigue on average than those with inactive CD. Adjusting for disease activity and type, other factors were also found to be independently associated with fatigue across time including poor sleep quality (F= 16.04,p<0.001), higher stress (F=6.89, p=0.01), distress (F=32.34,p<0.001) and higher C-reactive protein levels (F=4.20,p=.04). Conclusion: Fatigue may worsen over time in IBD, even when disease is in remission. Changes in psychological factors are associated with changes in fatigue across time, suggesting that they may be a useful target for intervention in order to impact fatigue. Fatigue levels at baseline, year 1 & 2 for CD and UC across disease activity patterns