A Concise History of Thiopurines for Inflammatory Bowel Disease: From Anecdotal Reporting to Treat-to-Target Algorithms

Background: The need for immune suppressive strategies in the control of chronic inflammatory bowel diseases originated in the 1960s following the perception of a relative inefficacy of salazopyrin and its derivatives. In some 50 years upon an anecdotal claim, the indication for thiopurines in the management of inflammatory bowel diseases has come of age. Objective: The aim of this minireview is to give an overview, after the historical premises, of the current use of thiopurines in the context of inflammatory bowel diseases. Method: Through MEDLINE searches, we reviewed the literature of the last two decades. Results: For Crohn's disease, the 1980 trial of 6-mercaptopurine for steroid sparing and fistula closure proved pivotal. The analysis of withdrawal experiments and of numerous open trials has established the efficacy of thiopurines for ulcerative colitis. In this indication, cutting-edge data are now showing that because targeting dysplasia, thiopurines can induce mucosal/histological healing, thus abolishing or delaying the need for pre-emptive (tumor prophylactic) colectomy. Conclusion: In UC thiopurines may be recognized to effect a treat-to-target strategy, joining the modern algorithms of rheumatologic disorders.