Monoclonal antibodies in the management of asthma: Dead ends, current status and future perspectives

Abstract

Patients with moderate-to-severe asthma may now be treated using a variety of monoclonal antibodies that target key inflammatory cytokines involved in disease pathogenesis. Existing clinical data on anti-IgE, anti-IL-5 and other immunological pathways indicate these therapies to offer reduced exacerbation rates, improved lung function, greater asthma control and better quality of life. However, as several patients still do not achieve satisfactory clinical response with the antibodies available, many more biologics, aiming different immunological pathways, are under evaluation. This review summarizes recent data on existing and potential monoclonal antibodies in asthma. Recent advances have resulted in the registration of a new antibody targeting TSLP (tezepelumab), with others being under development. Some of the researched monoclonal antibodies (e.g. anti-IL-13 tralokinumab and lebrikizumab or anti-IL-17A secukinumab) have shown optimistic results in preliminary research; however, these have been discontinued in asthma clinical research. In addition, as available monoclonal antibody treatments have shown little benefit among patients with T2-low asthma, research continues in this area, with several antibodies in development. This article summarizes the available pre-clinical and clinical data on new and emerging drugs for treating severe asthma, discusses discontinued treatments and outlines future directions in this area.

Baseline Characteristics of Patients Enrolled in Clinical Trials of Biologics for Severe Asthma as Potential Predictors of Outcomes

“…In the subpopulation of patients with asthma, BEC ≥ 150 cells/µL, and total IgE 30–700 kU/L, dupilumab showed a greater reduction in exacerbation rate and improvement in FEV 1 compared to omalizumab and mepolizumab. Not only is it difficult to compare the efficacy of mAbs, the very development of these agents has also always been very complex, as demonstrated by the numerous biologics that have failed during RCTs [ 98 ].…”

Emerging role for interferons in respiratory viral infections and childhood asthma

“…Together, these data suggest that the balance between T2 inflammation and type I interferon/IRF7 responses may stem from the bone marrow, far from the site of peripheral inflammation, as reported in other contexts ( 56 ). They also highlight the potential for new biologic drugs targeting TSLP ( 57 , 58 ) and the downstream effectors IL-13 and IL-17A ( 59 ) to attenuate inflammatory responses to RSV infection in early life.…”

Repositioning baloxavir marboxil as VISTA agonist that ameliorates experimental asthma

“…These drugs significantly improved lung function, decreased exacerbation rates, and provide better asthma control. However, some patients still fail to obtain remission after medication (Kardas et al 2022 ). Therefore, developing novel targets for asthma is crucial.…”