On the Horizon: Promising New Drugs for Unresponsive Asthma

By Brenda L. Mooney, MDalert.com Contributor
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Knowledge of the factors that contribute to the development of severe refractory asthma are exploding, offering hope to patients who have had few treatment options until now. A greater understanding of the disease’s molecular biology and immunogenetics has ushered in exciting new therapeutic approaches.

The primary beneficiaries of this groundbreaking work, according to a new review in the Journal of Asthma and Allergy, are patients with inadequate asthma control and those who bear the side effects of systemic steroids.

Asthma. (Source: Creative Commons 3)

The study’s researchers point out that, in the last decade or so, the monoclonal antibody (mAb) omalizumab has been the only available biologic therapy for these patients. Because it targets anti-IgE, omalizumab helps just a specific subpopulation of patients with uncontrolled IgE-mediated allergic asthma.

Other asthma sufferers not eligible or responsive to the treatment have had to wait for the development of different therapies. The review discusses promising new drugs and nonpharmacologic options such as biologic therapies with different mechanisms of action and targets.

“One of these molecules, the anti-interleukin 5 (anti-IL-5) mAb mepolizumab, has been recently approved for marketing,” the authors wrote. “Other mAbs and new anti-inflammatory agents, such as prostaglandin receptor antagonists, will be available in the coming years.”

Other promising drugs likely will be available in the near future, such as reslizumab, benralizumab, dupilumab and lebrikizumab, they add.

The report also touts nonpharmacologic therapies, such as bronchial thermoplasty (BT). While still controversial because of mixed research on effectiveness, the authors suggest it demonstrates “extremely interesting results in terms of improving the quality of life (QoL) and reducing asthma exacerbation.”

The challenge of identifying patients who would benefit the most from innovative therapies while limiting therapeutic dropouts remains, however. An answer could lie in the identification of new biomarkers, the researchers state.

“The development and application of a broader scale of reproducible, noninvasive, cheap and validated biomarkers will make the treatment selection easier, but those already available, if properly used, can guide the clinician to the right therapeutic option for the right patient,” they said.

In clinical practice, asthma management and its follow-up are mainly based on respiratory function parameters that determine hyperreactivity and bronchial obstruction, but the study authors note that the approach does not always define the levels and types of respiratory inflammation. At the same time, while fibrobronchoscopy and bronchoalveolar lavage are the “gold standard” for defining inflammation, they also are invasive and not routinely applicable, the researchers add.

That’s why they consider development of effective biomarkets so critical. One biomarker the study identifies as promising is periostin, an extracellular matrix protein that is also associated with eosinophilic flogosis and is primarily studied to predict the response and monitor the biodrugs such as lebrikizumab and omalizumab.

Some questions remain about its use, including exactly how it correlates with eosinophilic inflammation. The study adds that periostin is not just an indicator of type 2 inflammation activated by IL-13. Patients with asthma and high periostin levels often have singular characteristics, including eosinophilia, high levels of nitric oxide, acetylsalicylic acid intolerance, nasal polyposis and late-onset asthma.

“These features are probably correlated with the involvement of periostin in bronchial remodeling, and this protein may also be associated with poor response to corticosteroids, probably due to tissue remodeling,” the authors said. “In addition, periostin has an accurate predictive power of response to mAbs such as lebrikizumab, tralokinumab and omalizumab, especially if combined with other parameters such as the level of blood eosinophilia and FeNO.”

An initiative funded by the European Commission Innovative Medicines Initiative of the European Union has proposed a systematic algorithmic approach to patients with severe asthma. The Unbiased BIOmarkers in PREDiction of Respiratory Disease Outcomes project, which is part of the European Innovative Medicines Initiative, grew out of the increasing interest in the identification of biomarkers to guide identification and choice of innovative therapies for severe asthma, the study stated.