As noted in this blog (Only one chance to make first impression) and other sites as well, many have argued for early “top down” treatment to try to modify the natural history of Crohn’s disease (CD).  Early in the course of CD when an inflammatory process predominates, theoretically, treatment at this time point can prevent the development of intestinal fibrosis/strictured IBD phenotype.

Support for this approach can now be extrapolated from a mouse model as well (Inflamm Bowel Dis 2012; 18: 460-71).  In this study, the authors eliminated an inflammatory stimulus, Salmonella typhimurium, with levofloxacin treatment.  Treatment was initiated at sequential time points during infection.  Subsequently, the effects of the inflammation on the development of fibrosis was determined by examining histopathology; in addition, the effects on mRNA expression and protein expression were determined.  The time course of a number of cytokines is followed including TNFα, TGFβ, IL12p40, IL-17, IL-1β, and IL-6. While intestinal fibrosis developed even in those with early treatment, early treatment lessened, but did not eliminate, the development of fibrosis.

Since no effective antifibrotics exist and fibrosis may autopropagate even in the absence of inflammation, the authors postulate that early effective treatment has the best opportunity to alter the natural history.