Biologics in Asthma—The Next Step Toward Personalized Treatment

Abstract

Asthma is a multifaceted disease and is associated with significant impairment and risk, and a therapeutic response that is highly variable. While current treatments are usually effective for patients with mild to moderate disease, patients with more severe asthma are often unresponsive to current efforts, and there remains a need for agents with properties which may achieve control in these individuals. There is ongoing research to identify bioactive molecules that contribute to the pathophysiology of asthma, and many of these have been identified as potential therapeutic targets to improve control of this disease. As a consequence of these efforts, monoclonal antibodies have been developed and tested as to their effectiveness in the treatment of asthma. The assessment of these new treatments has identified particular pathways which, in selected patients, have shown benefit. The following review will discuss the current and future use of biological agents for the treatment of asthma, their efficacy, and how certain patient phenotypes and endotypes may be associated with biomarkers which may be used to select treatments to achieve greatest effectiveness of their use. As knowledge of the effects of these biological agents in asthma emerge, as well as the patients in whom they are most beneficial, the movement toward personalized treatment will follow.

Personalised medicine: are we ready?

“…So far it is without any doubt in severe eosinophilic asthma that personalised medicine has been the most successful. In this regard, phenotyping based on high blood eosinophilic count has proved to be essential to predict good clinical response to anti-interleukin-5 (>300-500 eosinophils·µL −1 ) and anti-IgE (>260 eosinophils·µL −1 ), in asthmatics uncontrolled by moderate to high doses of inhaled corticosteroids (ICS) combined with long-acting β-agonists [20]. Therefore, the best biomarker to use biologics in severe T2 asthma is rather simple (blood cell count) and somewhat contrasts with the great deal of sophisticated research that has been needed to establish the role of IgE and interleukin-5 in severe asthma and to characterise T2 asthma.…”

“…One interesting finding from the U-BIOPRED study is the identification by transcriptomics of a cluster with heavy airway neutrophilic inflammation, proteasome activation and tumour necrosis factor (TNF)-α expression, a cluster named TAC2 (transcriptome-associated cluster 2). This observation could reopen the way for anti-TNF-α treatment in severe asthma, a field which was closed based on the lack of convincing effect of golimumab (a monoclonal TNF-α-blocking antibody) on a cohort of severe asthmatics who were however not selected on the basis of their airway inflammatory profile [20]. Knowing that at least 50% of severe asthmatics are eosinophilic asthmatics [18] and that sputum cells from eosinophilic asthmatics produce less TNF-α than those of their noneosinophilic counterparts [22], it is conceivable that the effect of anti-TNF-α treatment would have been better if the study had selected noneosinophilic and neutrophilic asthmatics in particular.…”

New techniques for studying airway drug pharmacokinetics for asthma therapeutics

“…Biologics are increasingly used in asthma, one approved (omalizumab [22], and several in late-phase development [23]. Examples of inhaled biologics are rare, including inhaled insulin (e.g.…”

Primary Results of Long-Term Dynamic Monitoring of Children With Bronchial Asthma of Uncontrolled Severe Persistent Course

“…В связи с этим разрабатывается множество новых таргетных биологических препаратов для лечения БА [9]. На сегодняшний день омализумаб остается одним из наиболее длительно используемых моноклональных антител у детей с тяжелой и среднетяжелой неконтро-лируемой БА [10].…”