New medications for the treatment of Pediatric Asthma

New medications  for the treatment of Pediatric Asthma

  1. Khalilzadeh, M.D,Professor of Pediatric Pulmonology,

Shahid Beheshti University

Iranian Society of Pediatric Pulmonology

Abstract:

Asthma is the most common chronic disease in children. According to the international guidelines, the main goals of asthma treatment are symptoms control and lung function preservation, through a stepwise and control-based approach.

Age specific therapy are proposed in steps, according to clinical severity and the level of disease control. If control is not achieved within 3 months, stepping-up should be considered; otherwise, if control is achieved after 3 months, stepping down may be considered. The most used drug classes of asthma medications are beta-2 adrenergic agonists, corticosteroids, and leukotriene modifiers.

The quality of asthma diagnosis and management globally still needs substantial improvement. From infancy to the teenage years, there are age-specific challenges, including both under diagnosis and over diagnosis with stigma-related barriers to treatment in some cultures and in adolescents. Therefore, the interest in the development of new drugs and in the application of therapies currently used in other conditions for pursuing asthma control is needed.

Introduction:

Asthma is the most common chronic condition of childhood, and its management represents part of the daily activity of most professionals who deal with pediatric care. At any age, the main purposes of asthma treatment are to reduce exacerbations and to limit the progressive loss of lung function, thus decreasing the use of health resources and improving quality of life., In  more than one third of all patients with asthma the persistence of clinical symptoms, often associated with overt lung function abnormalities, indicate poor control, with the proportion increasing to >50% in adolescents.

A  trial was performed to evaluate  the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children.  Vestri  Study assessed 6208 asthmatic patients 4 to 11 years of age who required daily asthma medications and had a history of asthma exacerbations in the previous year efficacy and safety of fluticasone propionate plus salmeterol or fluticasone alone for 26 weeks. The result showed that the risk of a serious asthma-related event with salmeterol in a fixed-dose combination with fluticasone was similar to the risk with fluticasone alone.

The first-line escalation after addition of either a long-acting β۲-agonist is adding  a leukotriene receptor antagonist (LTRA). This is followed by the addition of a long-acting muscarinic antagonist (LAMA) [tiotropium] or biologic treatments .

Novel biologic drugs (i.e., Omalizumab,  dupilumab, mepolizumab, reslizumab, and benralizumab) seem to be promising in reducing annual exacerbation rates and steroid-use in glucocorticoid-dependent cases, but available data are few and limited to adolescents and adults.

Omalizumab:

Allergen sensitization and high frequencies of comorbid allergic diseases are characteristic of severe asthma in children. Omalizumab, an anti-IgE mAb, is the first targeted biologic therapeutic approved for the treatment of moderate-to-severe persistent allergic asthma that remains uncontrolled despite high-dose inhaled corticosteroids plus other controller medications.  Treatment with omalizumab, the first anti-immunoglobulin E recombinant humanized monoclonal antibody, has been definitely approved in pediatric uncontrolled asthma in  children aged > 6 years .

The existing evidence confirmed  that omalizumab therapy reduces asthma exacerbations  and healthcare utilization, has a steroid-sparing effect and improves lung function. According to the multicenter studies , omalizumab is an effective and safe add-on therapy in uncontrolled severe allergic asthma in children.

Mepolizumab:

First approved in 2015 for severe eosinophilic asthma, mepolizumab is the first-in-class monoclonal antibody that targets IL-5. It is believed to work by preventing IL-5 from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this way reduces blood eosinophils without completely depleting them. In the US, Nucala (100mg subcutaneous injection of mepolizumab) is currently licensed as an add-on maintenance treatment for patients with severe eosinophilic asthma aged 12 years and older. This now extends to patients aged six to 11 years (40mg dose subcutaneous injection).

 Tiotropium :

Totropium is a LAMA that primarily acts as a long-acting form of anticholinergic bronchodilator .The GINA guidelines include tiotropium delivered by mist inhaler as an add-on therapy option at Steps 4 and 5 in patients aged ≥ ۱۲ years with a history of exacerbations despite treatment with ICS and LABAs and tiotropium recently been approved for use as once-daily maintenance therapy for children with asthma over the age of 6 years in the USA (February 2017).

Tiotropium  is a useful and novel add-on treatment option, especially in patients where standard therapy with moderate-to-high ICS with or without a LABA does not result in sufficient asthma control.

 Macrolide Antibiotics:

Macrolides are widely used antibiotics with both antimicrobial and anti-inflammatory activities . Indeed, macrolides may reduce airway inflammation either by acting on pro-inflammatory cytokines or by controlling intracellular infection which may trigger and maintain inflammation

At present, the role of macrolides in pediatric severe asthma is controversial and their administration is not recommended routinely, but may be considered in children with neutrophilic asthma for reducing daily oral steroids administration and improving lung function.

Conclusion:

Despite the availability of several novel therapeutic strategies for uncontrolled asthma, future trials targeted at specific pediatric age subgroups are needed to support evidences of safety and efficacy also in children.

References:

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http://www.asthma.org.uk/about/media/facts-and-statistics/. Accessed 14 Nov 2017.

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