Rationale for the use of immunomodulatory therapies in the Global Initiative for Asthma (GINA) step V asthma other than oral glucocorticosteroids.

Asthma is a major problem worldwide, which is estimated to affect 300 million individuals. The global prevalence ranges from 1% to 18% of the population. The incidence, morbidity and mortality of the condition have increased over the last 50 years despite the development of new anti-asthmatic drugs. Fewer than 1% of the asthmatic population are steroid-dependent, but these patients consume most of the resources and time at asthma units. The consensus documents published by professional societies all support a stepwise therapeutic approach for asthma. However, patients who require frequent or continuous oral corticosteroid administration have received little attention. Due to the severe side-effects of oral corticosteroids when administered over long periods or at high doses, many drugs have been assessed in the search for a possible corticosteroid-sparing agent. Recently, the update of the Global Initiative for Asthma (GINA) introduced a new drug--omalizumab--as an alternative to oral corticosteroids in patients included in step V. Other alternatives include immunosuppressive drugs, among which methotrexate has been found to offer the best benefit/risk ratio. This paper will review, comment and criticize the evidence of the effectiveness of immunomodulatory drugs, as an alternative to oral glucocorticosteroid treatment in GINA step V asthma patients. The experience of the authors combined with the information of the literature will lead to the conclusion that methotrexate and omalizumab are the only advisable drugs and will clarify when and how these drugs should be used.