Journal of Asthma and Allergy (Sep 2021)
Intranasal Corticosteroids: Topical Potency, Systemic Activity and Therapeutic Index
Abstract
Peter T Daley-Yates,1 Désirée Larenas-Linnemann,2 Chaitanya Bhargave,3 Manish Verma3 1Clinical Pharmacology and Experimental Medicine, GlaxoSmithKline plc., Research and Development, Uxbridge, UK; 2Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico; 3Respiratory and Allergy, GlaxoSmithKline plc., Mumbai, IndiaCorrespondence: Peter T Daley-YatesClinical Pharmacology and Experimental Medicine, GlaxoSmithKline plc., Research and Development, Uxbridge, UKTel +44 208 990 2460Fax +44 208 990 3501Email [email protected]: Intranasal corticosteroid (INCS) therapy is the preferred treatment option for allergic rhinitis (AR). Although all INCSs for the treatment of AR are considered safe and effective, differences in potency, molecular structure features and physicochemical and pharmacokinetic properties could result in differences in clinical efficacy and safety. Higher glucocorticoid receptor (GR) binding affinity of INCS is associated with higher lipophilicity, nasal tissue retention and topical potency. Higher topical potency is also accompanied by low oral bioavailability and high systemic clearance conferring low systemic exposure, reduced potential for systemic adverse effects and an improved therapeutic index. It has been shown that adverse events related to systemic exposure of INCSs in children are low. Although INCSs mostly produce low systemic effects, use of an INCS with low systemic exposure in patients on multiple corticosteroid (CS) therapies could help reduce the total systemic burden of CS therapy. Despite differences in topical potency, physicochemical and pharmacokinetic properties between INCSs, clinical studies of INCSs in the treatment of AR generally show no clinically important differences between these compounds, and poor correlation between INCS topical potency and clinical response. However, the lack of head-to-head comparisons of INCSs in clinical studies conducted in more severe AR patients should be noted. This narrative review provides an assessment of the therapeutic relevance of topical potency and the physicochemical and pharmacokinetic properties of INCSs and describes for the first time the relationship between topical potency and therapeutic index using pharmacological features of INCSs. It concludes that higher GR binding affinity and topical potency can potentially improve the therapeutic index of an INCS. Therefore, both efficacy and systemic exposure profiles should be considered when comparing INCS regimens in terms of therapeutic equivalence, to aid clinical decision-making and avoid the assumption that all INCS formulations are the same when considering treatment options.Keywords: corticosteroid, intranasal, topical potency, rhinitis therapeutic index
