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

Abstract

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.

Dual Monoclonal Antibody Therapy for a Severe Asthma Patient

“…Until omalizumab was first marketed in 2006, the international guidelines considered oral corticosteroids (OCs) to be the final step in the treatment of severe asthma patients ( Domingo et al., 2007 ). The use of certain immunosuppressive drugs was also proposed ( Domingo et al., 2009 ; Domingo et al., 2011a ) although they were not included in the guidelines. With the advent of biological treatments linked to the concept of precision medicine ( Jameson and Longo, 2015 ), it became necessary to phenotype patients ( Wenzel, 2012 ), and more recently to endotype them ( Lötvall et al., 2011 ).…”

Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study

“…6 This reduction in OCS use is of importance because treatment with OCSs has a considerable impact on patients' lives owing to the associated corticosteroid-related adverse effects. [9][10][11] While all 3 studies reported the prevalence of adverse events (AEs) and assessed basic safety variables, the long-term safety and durability of the response to subcutaneous mepolizumab in patients with severe eosinophilic asthma are not fully established.…”

Effect of Kuwanon G Isolated from the Root Bark of Morus alba on Ovalbumin‐induced Allergic Response in a Mouse Model of Asthma

“…In chronic asthma, inhaled/intravenous corticosteroids and magnesium sulphate are used in addition to long‐acting beta agonists, leukotriene receptor antagonists, anticholinergic medications (Shepherd et al , ), or mast cell stabilizer. However, patients who require frequent or continuous treatment of these medications receive little or no benefit because of the severe side effects when administered over long periods or at high doses (Domingo et al , ). Therefore, safer preventive and therapeutic agents for asthma need to be developed.…”