Improving the risk-to-benefit ratio of inhaled corticosteroids through delivery and dose: current progress and future directions

ABSTRACT

Introduction

Inhaled corticosteroids (ICS) are known to increase the risk of systemic and local adverse effects, especially with high doses and long-term use. Hence, considerable resources are invested to improve pharmacokinetic/pharmacodynamic (PK/PD) properties of ICS, effective delivery systems and novel combination therapies to enhance the risk-to-benefit ratio of ICS.

Areas covered

There is an unmet need for new solutions to achieve optimal clinical outcomes with minimal dose of ICS. This paper gives an overview of novel treatment strategies regarding the safety of ICS therapy on the basis of the three most recent molecules introduced to our everyday clinical practice – ciclesonide, mometasone furoate, and fluticasone furoate. Advances in aerosol devices and new areas of inhalation therapy are also discussed.

Expert Opinion

Current progress in improving the risk-to-benefit ratio of ICS through dose and delivery probably established pathways for further developments. This applies both to the improvement of the PK/PD properties of ICS molecules but also includes technical aspects that lead to simplified applicability of the device with simultaneous optimal drug deposition in the lungs. Indubitably, the future of medicine lies not only in the development of new molecules but also in technology and digital revolution.

KEYWORDS:

• Delivery devices
• dose adjustment
• combination therapy
• future treatments
• inhaled corticosteroids
• safety

Article highlights

• Inhaled corticosteroids (ICS) are known to increase the risk of systemic and local adverse effects (AEs), especially with high doses and long-term use. Therefore, the maximal achievable ICS dose reduction while maintaining optimal lung disease control can be considered the highest clinical priority to enhance the safety of treatment.

• The new ICS have unique pharmacodynamic and pharmacokinetic properties, resulting in a favourable risk-benefit profile and once-daily dosing regimens, which improve treatment adherence.

• Due to the synergistic action of all compounds, fixed-dose combination therapy allows the use of a lower daily ICS dose while maintaining a comparable therapeutic effect.

• Considering the overall safety, effectiveness and patient adherence, a once-daily-single-inhaler combination therapies represent a beneficial treatment strategy in clinical practice and may be an emerging tool for the stepwise ICS dose reduction.

• More efficient drug delivery allows the use of a lower nominal ICS dose and may reduce the rate of local AEs without undermining the treatment outcomes. However, considering that most of currently available ICS present a negligible oral bioavailability (<1%) more efficient lung delivery at a reduced nominal dose is therefore unlikely to result in a clinically significant reduction in systemic side effects in most circumstances.

• There is some evidence that extrafine-particle ICS compared with fine-particle ICS offer advantage by targeting specific, hard-to-reach areas of the diseased lung and may display lower risk of both pneumonia in patients with chronic obstructive pulmonary disease and oropharyngeal effects of ICS.

• Efficacy and safety are improved by reducing the complexity of treatment regimens, simplification of the inhalation process as well as various dose-feedback systems that prevent inhalation errors.

This box summarizes key points contained in the article.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have consulted for the following companies: Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Synairgen, Teva, Theravance and Verona. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interests

P Kuna reports personal fees from Adamed, AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Hal Allergy, Lekham, Mylan, GSK, Novartis, Polpharma, Sanofi, and Teva, outside the submitted work. M Kupczyk reports personal fees from Adamed, ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Lekam, Alvogen, Emma, Nexter, Teva, and Berlin Chemie, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.