Phosphodiesterase 4 inhibitors and inflammatory bowel disease: emerging therapies in inflammatory bowel disease

Abstract

Crohn's disease and ulcerative colitis (UC) are common, chronic inflammatory bowel diseases (IBDs) characterized by episodes of life-altering symptoms such as diarrhea, bleeding, fecal urgency and incontinence, abdominal pain and cramps, and fever lasting weeks to months at a time. Existing treatments are 5-aminosalicyclates or immunosuppressants, but long-term control of IBD is a major problem for a large number of patients. Phosphodiesterase 4 (PDE4) is a key enzyme in cell homeostasis and inflammation and its inhibition has been useful in diseases such as asthma and chronic obstructive pulmonary disease, rheumatoid arthritis and multiple sclerosis. This review focuses on the role of oxidative stress in IBD and the PDE4 inhibitor OPC-6535 (tetomilast), an investigational agent for the treatment of UC. The authors detail the clinical development of the compound and report and provide insight into some of the unpublished data from the recently completed multicenter Phase III trials in UC.

Keywords::

• Crohn's disease
• phosphodiesterase
• reactive oxygen species
• tetomilast (OPC-6535)
• ulcerative colitis

Acknowledgements

The authors thank S Choudhary for his assistance in preparation of the manuscript and are grateful to Otsuka Pharmaceuticals for providing data on pharmacodynamics, pharmacokinetics, clinical safety and Phase III studies of tetomilast.

Disclosure

JP Guzman is an employee of Otsuka Pharmaceutical Development and Commercialization, Inc. (formerly Otsuka Maryland Research Institute). A Keshavarzian and A Banan have no conflict of interest to declare and no fee has been received for the preparation of the manuscript.

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