Holy Grail: the journey towards disease modification in asthma

Abstract

At present, there is no cure for asthma, and treatment typically involves therapies that prevent or reduce asthma symptoms, without modifying the underlying disease. A “disease-modifying” treatment can be classed as able to address the pathogenesis of a disease, preventing progression or leading to a long-term reduction in symptoms. Such therapies have been investigated and approved in other indications, e.g. rheumatoid arthritis and immunoglobulin E-mediated allergic disease. Asthma's heterogeneous nature has made the discovery of similar therapies in asthma more difficult, although novel therapies (e.g. biologics) may have the potential to exhibit disease-modifying properties. To investigate the disease-modifying potential of a treatment, study design considerations can be made, including: appropriate end-point selection, length of trial, age of study population (key differences between adults/children in physiology, pathology and drug metabolism) and comorbidities in the patient population. Potential future focus areas for disease-modifying treatments in asthma include early assessments (e.g. to detect patterns of remodelling) and interventions for patients genetically susceptible to asthma, interventions to prevent virally induced asthma and therapies to promote a healthy microbiome. This review explores the pathophysiology of asthma, the disease-modifying potential of current asthma therapies and the direction future research may take to achieve full disease remission or prevention.

Precision medicine in complex diseases—Molecular subgrouping for improved prediction and treatment stratification

“…For the right patient, a dramatic treatment response can be observed with marked symptom reduction and increased quality of life. For severe asthma patients, there are today several biological drugs available, including omalizumab (anti-IgE), mepolizumab (anti-IL5), benralizumab (anti-IL5R), dupilumab (anti IL4/IL13), and tezepelumab (anti-TSLP) [43]. A clinical challenge is to predict which patient will respond to which treatment.…”

Remission: Mission Possible in Chronic Rhinosinusitis with Nasal Polyposis?

“…Recent application of these concepts to the management of inflammatory airway disease has promoted the concept of clinical remission, using a "Treat to Target" approach. The concept of remission, now well-established in Rheumatology as well as Gastroenterology (GI), is emerging in Respiratory Medicine with recent publication of definitions of clinical remission for asthma (1). It is interesting to consider whether the disease remission concept might successfully be applied to Otolaryngology-Head and Neck Surgery (OHNS) in the management of chronic rhinosinusitis with nasal polyposis (CRSwNP).…”

Early priming of asthma and respiratory allergies: Future aspects of prevention

“…After a broader use of biologics for the treatment of allergic diseases in pediatric populations became possible, the vision of a therapy more closely related to the underlying pathophysiology of an individual patient has come more into reach. 80 Until now, the application of biologics has been quite expensive (ie high direct costs) and for this reason limited to use in more severe patient groups. But it is more than a dream to postulate that biologics will emerge from the status of "reserve medications" for difficultto-treat patients toward first-line treatment options especially for the younger patient group where the disease is still developing and progress into more severe and/or comorbid endotypes might be preventable.…”

“…However, so far, none of them has been proven effective in preventing the onset of asthma and modifying the natural history of the disease. After a broader use of biologics for the treatment of allergic diseases in pediatric populations became possible, the vision of a therapy more closely related to the underlying pathophysiology of an individual patient has come more into reach 80 . Until now, the application of biologics has been quite expensive (ie high direct costs) and for this reason limited to use in more severe patient groups.…”