Small-particle inhaled corticosteroids: Paradigm shift in asthma treatment

When large-particle inhaled corticosteroids (ICS) used as a monotherapy fail to control asthma, the current asthma guidelines recommend “stepping up” therapy by adding long-acting beta 2 agonists (LABAs) to the regimen as a first-line alternative treatment approach. Recent research, however, has shown that pediatric patients with uncontrollable asthma would not only benefit more from the administration of small-particle ICS used as a monotherapy in this scenario, but that small-molecule ICS treatment should be considered as the foundation of the management of asthma in children, heralding a potential paradigm shift from traditional asthma therapy.

David Price, MD“The treatment of asthma in children can be challenging and the choices of treatment are often complex. Standard size-particle ICS has already been established as an effective first-line treatment approach for acute episodes of asthma. However, this approach can sometimes fall short of its therapeutic goal. In still uncontrollable asthma, stepping up therapy with the addition of LABAs to the ICS regimen has shown to be effective where standard size-particle ICS therapy used as a monotherapy fails. The use of small-particle ICS, however, has gained favor among clinicians and their patients in part due to the simplification of the dose regimen for asthma management in this patient population, coupled with at least equivalent efficacy in observational studies,” says David Price, MD, professor of Primary Care Respiratory Medicine, Academic Primary Care, University of Aberdeen, United Kingdom.

The most commonly used small-particle ICS agents in the United States include beclomethasone dipropionate and fluticasone dipropionate. One of the main advantages of small-particle ICS is that these agents have an improved total lung deposition and, therefore, lower daily doses are required to achieve an effective control of asthma when compared with large-particle ICS drugs. In addition, small-particle ICS agents are able to reach the small airways, which may result in an increased treatment efficacy leading to a quicker resolution of symptoms.

Price and colleagues recently conducted an electronic records review study of children with asthma aged 5 to 11 years comparing the efficacy between small-particle ICS treatment and standard size-particle ICS treatment when initiating or stepping up ICS treatment for their disease, as well as small-particle ICS and standard size-particle ICS with the addition of LABA to the regimen.¹ Variables were measured during 2 consecutive years (1 baseline year for confounder definition and 1 outcome year), including risk-domain asthma control and rate of severe exacerbations.

In the initiation population cohort, those children who were prescribed small-particle ICS (n=797) experienced greater odds of asthma control as well as a lower severe exacerbation rate when compared with those who received standard size-particle ICS therapy (n=797). Similarly, it was found that step-up treatment outcomes were significantly more favorable in the small-particle ICS cohort compared with the standard size-particle ICS cohort.

Results also showed that the number needed to treat with small-particle ICS to achieve 1 additional child with asthma control was 17 for the initiation cohort and 5 for the step-up cohort. The data did not show any significant differences in outcome between those patients who received stepped-up small-particle ICS treatment (n=185) when compared with those who received ICS plus LABA combination therapy (n=185).

The results not only clearly speak in favor of using small-particle ICS therapy for acute bouts of asthma, but they also suggest that small-particle ICS could be considered as the drug of choice for the long-term management of this disease in the pediatric population. Moreover, the use of small-particle ICS appears to be more practical and can result in lower overall healthcare costs for this patient population because there is no need to have a combination inhaler at the ready or a prescription for ICS plus LABA should the patient require stepping up treatment.

Clinicians frequently rely on evidence from randomized controlled trials (RCT) for guidance in their choice of asthma therapy. Unfortunately, however, such trials are few and far between mostly because of the large costs associated with RCTs. Moreover, RCTs do not always represent a complete cross-section of the asthma patient population under scrutiny, says Price, and they can often exclude those patients with milder disease who are also more prone to disease exacerbations. As such, the outcomes of observational design studies can often prove to be very valuable in helping clinicians optimally treat and manage their patients.

“According to the evidence, small-particle ICS should be the treatment of choice for acute asthma episodes in pediatric patients, a notion that challenges the status quo of current asthma therapy in children,” says Price. “Although further studies need to be performed to confirm these results, we believe that our data firmly supports small-particle ICS as the optimal treatment approach for asthma in the pediatric population,” he adds.

Reference

1. van Aalderen WM, Grigg J, Guilbert TW, et al. Small-particle inhaled corticosteroid as first-line or step-up controller therapy in childhood asthma. J Allergy Clin Immunol Pract. 2015;3(5):721.e16-731.e16.

Dr. Price has received research support from Teva; is a member of the following boards for which fees were paid to RiRL: Aerocrine, Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, and Teva; has received consultancy fees paid to RiRL from Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Pfizer, and Teva; has received research support for which fees were paid to RiRL from UK National Health Service, British Lung Foundation, Aerocrine, AstraZeneca, Boehringer Ingelheim, Chiesi, Eli Lilly, GlaxoSmithKline, Meda, Merck, Mundipharma, Novartis, Orion, Pfizer, Respiratory Effectiveness Group, Takeda, Teva, and Zentiva; has received fees (paid to RiRL) for manuscript preparation from Mundipharma and Teva; has received travel reimbursement from Aerocrine, Boehringer Ingelheim, Mundipharma, Napp, Novartis, and Teva; has received funding paid to RiRL for patient enrollment or completion of research from Almirall, Chiesi, Teva, and Zentiva; has received unrestricted funding, paid to RiRL, for investigator-initiated research from Aerocrine, AKL Ltd, Almirall, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, Orion, Takeda, Teva, and Zentiva; has a pending patent for Phytopharmaceuticals with AKL Ltd; has shares in AKL Ltd, which produces phytopharmaceuticals; and owns 80% of RiRL Ltd and its subsidiary social enterprise Optimum Patient Care; and is peer reviewer for grant committees: Medical Research Council (2012), Efficacy and Mechanism Evaluation programme (2012), and HTA (2012).