Inflammatory Bowel Disease: New Therapeutic Options in the Post Anti-TNFα Era

Abstract

Background: Inflammatory bowel diseases are chronic bowel disorders the causes of which have not been fully elucidated, though they all sharean immunological basis. They have an important impact on both quality of life of the patient and on healthcare services.

Method: The incorporation of biological agents against tumour necrosis factor (TNF) alpha some 15 years ago represented a revolution in the management of patients with disease that did not respond to conventional treatment, enabling an overall improvement in the quality of life of many of these patients.

Results: Nonetheless, these agents are not effective in an appreciable percentage of patients (primary lack of response), can lose their efficacy over time even though they were initially effective (loss of secondary response), and can also be burdened by varied and sometimes severe adverse effects (e.g., infusion reactions, infections, neoplasms). Consequently, basic research over recent years has provided us with promising new pharmacological agents aimed at targets other than TNF alpha (IL12/23, anti-adhesion molecules, Janus kinase inhibitors, anti- Smad7, blockade of sphingosine-1-phosphate receptors).

Conclusion: This paper reviews some of the key aspects of these new drugs, including their mechanism of action, some incipient pharmacokinetic and metabolic data, their efficacy and their safety. These new agents will take on an important role in the coming years in the management of patients with moderate-to-severe forms of inflammatory bowel disease.

Keywords: Adhesion blockade; Crohn´s disease; anti IL-12/23 therapies; anti-sense therapies; small molecules; ulcerative colitis.