Phosphodiesterase 4 inhibitors in inflammatory bowel disease: a comprehensive review

Inflammatory bowel disease (IBD) is known as a chronic inflammation of gastrointestinal tract that its pathogenesis still is not completely understood. Several drug categories are used for management of IBD but there is no exact cure for the disease, however biological drugs targeting the inflammation of gut are on the center of attention. In investigation into the anti-inflammatory drugs, phosphodiesterase inhibitors were found to be effective in different inflammatory disorders. Of them phosphodiesterase 4 (PDE4) inhibitors are considered for treatment of asthma and chronic obstructive pulmonary disease (COPD). Some of PDE4 inhibitors showed promising efficacy in animal studies, however to date no phase III clinical study showed their effectiveness in IBD. The present study has the most relevant studies in this field. PDE4 inhibitors affect IBD in different ways including anti-inflammatory, anti-depressant, and anti-fibrotic effects. Unfortunately, the most common side effect of PDE4 inhibitors is nausea which limits its use. Tetomilast the second generation of PDE4 inhibitors showed promising effects in phase II studies with better safety profile. Other drugs in this class are ongoing phase II and III trials.