One Size Does Not Fit All: The Case for Translational Medicine.

Yehuda Chowers

doi:10.5041/rmmj.10364

Abstract

Therapy for inflammatory bowel diseases (IBD) has developed during recent years. Despite the availability of new therapeutic modalities, overall therapy success remains modest, and complete remission is usually achieved and maintained in approximately 30% of patients only. This observation can be explained by a number of reasons. First, the involvement of multiple genetic loci combined with differential environmental exposures suggests that IBD represent a continuum of disorders rather than distinct homogeneous disease entities. This diversity is translated into different disease course patterns, wherein some patients experience quiescent disease whereas others suffer from a relentless disease course. Hence, basic disease pathogenesis sets the stage for differential treatment responses. To date, IBD therapy is based on immunosuppression which does not take basic disease variability into account. Treatments are prescribed based on statistical considerations related to the response of the average patient in clinical trials rather than on personal considerations. Treatment outcomes can potentially be improved if physiologic considerations are integrated into the drug selection process. In one approach, drugs can be targeted at known patient dysfunctional processes such as in the case of patients carrying autophagy-related genetic polymorphisms being treated with rapamycin, a drug that inhibits mTOR inhibitor and enhances autophagy. Another alternative would be to use a systems approach to perform unsupervised, high-throughput screening in order to derive predictive treatment biomarkers and mechanistic insights associated with response to specific drug therapy. Additional predictive markers for drug safety are needed as well. Caveats and directions for needed future studies are outlined.

Highlights

Inflammatory bowel diseases (IBD) are traditionally classified into Crohn’s disease (CD) and ulcerative colitis (UC)
The etiology and pathogenesis of CD and UC are still elusive despite multiple studies aimed at increasing our understanding of these issues
A generally accepted concept is that tissue damage is caused by immune activation, and both diseases are considered to originate from immune system dysfunction

Summary

INTRODUCTION

Inflammatory bowel diseases (IBD) are traditionally classified into Crohn’s disease (CD) and ulcerative colitis (UC). A careful balance of medical cost–benefit should be made before therapy selection This type of therapy should be prescribed either to patients who are symptomatic, or to those in whom disease is predicted to progress and cause significant tissue damage and functional loss. These therapies should be restricted only to patients who have a high chance to respond, preferably with a low risk for side effects. What can be the reasons for this relatively poor drug performance? An in-depth look into the complex etiology of IBD and the difficulty to predict disease course may offer some insights into this problem

COMPLEXITIES OF IBD AND DISEASE COURSE PREDICTION

ALTERNATIVE APPROACHES FOR THERAPY SELECTION

LOOKING TO THE FUTURE

Findings

CONCLUSION