New therapeutic avenues for treatment of fibrosis: can we learn from other diseases?

Crohn's disease (CD) is characterized by the frequent occurrence of complications, such as fibrotic strictures and subsequently the need for CD-related surgery. Chronic or recurrent inflammation is generally regarded to be a necessary precondition for the initiation of intestinal fibrosis. In this view, fibrosis is a pathologically augmented healing response to inflammation-induced mucosal tissue destruction and injury. At present, there are no approved or effective medical therapies aimed specifically at fibrosis or stricture in IBD. Indirect benefits may occur from anti-inflammatory therapies, although there is no consensus on this. Therapy for fibrosis is complicated by the fact that a wound-healing response is essential in CD and ulcerative colitis. Several pharmaceutical companies are now working on the therapy of fibrosis in other diseases. Strategies interfering with TGF-β expression and activation are promising. Pirfenidone has been studied in several clinical trials. Further therapeutic options are second-generation and wide-spectrum tyrosine kinase inhibitors. These inhibit growth factor receptor signaling, thus reducing fibrosis in animal models and some patients with tumor-associated fibrosis. At present, the development of antifibrotic therapies takes place in other diseases such as lung and liver fibrosis. This is partially due to a lack of experimental models for gut fibrosis and the fact that reliable readouts (MRI, serum markers) in patients are lacking. It will be important to test the above-mentioned newly available treatment strategies in IBD to profit from progress in other fibrotic diseases.