O2.2 Phosphodiesterase type-4 inhibitors

Phosphodiesterase type-4 (PDE-4) inhibitors act by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP) to suppress inflammation and bronchoconstriction. A Cochrane Review analysed results from RCTs of roflumilast (20 trials, 17,627 patients) and cilomilast (14 trials, 6,457 patients) (Chong 2017) [evidence level I]. Compared to placebo, PDE-4 inhibitors improved FEV1 (mean difference 51 ml, 95% CI 43 to 60, moderate quality evidence) and reduced exacerbation rates (OR 0.78, 95% CI 0.73 to 0.83, high quality evidence; NNTB 20, 95% CI 16 to 26), but had relatively small effects on quality of life and symptoms. Gastrointestinal adverse effects were more frequent with the PDE-4 inhibitors, and psychiatric adverse events such as insomnia and depressive mood symptoms were more frequent with roflumilast (OR 2.13, 95% CI 1.79 to 2.54). These oral agents are not currently available in Australia.