Strategies for improving the efficacy and therapeutic ratio of glucocorticoids

Although glucocorticoids are very effective in suppressing inflammation there is a clear clinical unmet need for new or improved glucocorticoids in patients with severe asthma and COPD. Recent developments include the targeted deposition of ultrafine glucocorticoid particles to treat small airways and the potential of novel agents that have a reduced side effect profile. Understanding the drivers of relative glucocorticoid resistance in these patients may lead to the development of newer drugs aimed at subsets of patients, for example asthmatics with high periostin levels. Alternatively, inhibitors of kinase pathways that are associated with inflammatory responses may be able to modulate glucocorticoid function and combinations of these inhibitors along with novel glucocorticoids may provide the combination therapy of the future.

► Unmet clinical need for new or improved glucocorticoids. ► Emphasises treatment-specific subphenotypes of disease. ► Drug deposition can markedly affect clinical efficacy of ICS. ► Rationale for new ICS-kinase inhibitors in severe asthma and COPD.