Safety and Adverse Events Associated With Inhaled Corticosteroids for Asthma

Children with severe asthma treated with inhaled corticosteroids (ICS) may be at increased risk of experiencing adverse events and should be considered for early treatment with a biological agent to potentially reduce the need for glucocorticosteroid use, according to a study published in the Journal of Allergy and Clinical Immunology: In Practice.

Researchers performed a literature review of the evidence regarding adverse events in children related to the use of ICS. The purpose of this study was to summarize the evidence regarding adverse events related to the use of ICS, focusing on individuals with asthma, and narrowing in on those with the most severe form of asthma. Adverse events examined included:

Hypothalamic-pituitary-adrenal (HPA) axis suppression

Results of a meta-analysis demonstrated an adrenal insufficiency prevalence range of 2.4% to 21.5% in children treated with low and high doses of ICS, respectively. Further, the researchers identified 100% risk for HPA axis suppression in patients treated with the correct dose and duration of ICS, and this risk can continue despite discontinuation of ICS treatment. Tests to examine the effects of ICS on the HPA axis are expensive, and these effects often go unrecognized and unreported. It is suggested that patients undergo regular examination and close follow-up of HPA axis integrity, although this may be difficult considering the potential increase in cost for such follow-up.

Reduction in growth velocity

The researchers found that inhaled beclomethasone 400 µg and mometasone 200 µg, but not ciclesonide 40 to 160 µg/d, were found to reduce growth velocity in children. Conflicting results regarding the use of inhaled budesonide were reported. Overall, growth reduction ultimately results in lower adult height in children receiving long-term treatment with ICS (>12 months), with studies showing minor effects on final height to be an average reduction in adult height by 1 cm. Clinicians should carefully monitor growth patterns and velocity in their pediatric patients placed on ICS, and should consider re-evaluation of their asthma medication regimens if a reduction in linear growth is observed.

Osteoporosis

Study results found that glucocorticoids reduce bone mineralization and increase bone resorption, thereby compromising the integrity of bones in patients treated with ICS and placing them at high risk for fracture. Women treated with ICS over a period of 6 months showed signs of significant bone deterioration, with up to 40% of postmenopausal women experiencing a fracture in their lifetime, as women are more prone to osteoporosis and osteoporosis-related fractures. Treatment of asthma with ICS in childhood places these children at higher risk for fracture and early predisposition to osteoporosis in adulthood. Clinicians should carefully monitor bone health in individuals using ICS and consider the use of fracture risk assessment tools such as FRAX^® or QFracture^®.

Diabetes

Use of ICS was found to be related to a 34% increase in the risk of developing incident diabetes, with higher risk in patients taking high-dose ICS. Clinicians should reconsider the use of ICS in patients currently taking oral hypoglycemic agents as ICS have the potential to worsen diabetes in this patient population. Children had an elevated average in Serum glucose levels were found to be elevated in children receiving long-term ICS (>6 months). Close glucose monitoring is therefore advised for individuals with asthma being treated with ICS, especially those diagnosed with diabetes.

Ophthalmic effects

While there has not been a definitive association between ICS and cataract formation, there was a significant association found between ICS use in elderly patients and the risk of severe cataracts requiring subsequent surgery. The meta-analysis suggests there is a modest risk for the development of cataracts and open-angle glaucoma associated with ICS use, with higher odds ratios associated with higher doses of ICS and longer duration of use. Clinicians should regularly monitor ocular pressure in patients placed on long-term ICS.

Respiratory infections

Multiple clinical trials reported increased risk of developing pneumonia in individuals with chronic obstructive pulmonary disease (COPD) placed on ICS, and case reports suggest ICS could cause viral infections; however, conflicting results have also been reported in other studies.  One study found an increased risk of developing tuberculosis with the use of fluticasone in individuals with chronic respiratory distress.

The researchers conclude that the use of ICS in children carries a high risk of multiple adverse events, with an increase in risk with each dose. Therefore, they suggest the early use of biologics in individuals with asthma, as well as others experiencing relevant ICS-related adverse events, that could potentially reduce the need for, and adverse event risk associated with, glucocorticosteroid therapy. In addition, clinicians should closely monitor individuals on ICS treated with biologics and consider stepping down the dosing of ICS as soon as the individuals demonstrate at least 3 months of asthma control and improvement

Reference

Heffler E, Nascimento Girardi Madeira L, Ferrando M, et al. Inhaled corticosteroids safety and adverse effects in patients with asthma [published online February 2, 2018]. J Allergy Clin Immunol Pract. doi:10.1016/j.jaip, 2018.01.025