An evaluation of roflumilast and PDE4 inhibitors with a focus on the treatment of asthma

ABSTRACT

Introduction: Asthma is a common chronic airway inflammatory disease characterized by diverse inflammatory events leading to airway hyperresponsiveness and reversible airflow obstruction. Corticosteroids have been the mainstay for asthma treatment due to their broad anti-inflammatory actions; however, other medications such as phosphodiesterase 4 inhibitors also demonstrate anti-inflammatory activity in the airways.

Areas covered: This review describes tissue expression of phosphodiesterase 4 in the airways, the different phosphodiesterase 4 isoenzymes identified, and the anti-inflammatory activities of phosphodiesterase 4 inhibition in asthma and related findings in chronic obstructive pulmonary disease (COPD). The authors further review clinical trials demonstrating that drugs such as roflumilast have an excellent safety profile and efficacy in patients with asthma and COPD.

Expert opinion: Phosphodiesterase 4 inhibitors suppress the activity of immune cells, an effect similar to corticosteroids although by acting through different anti-inflammatory pathways and uniquely blocking neutrophilic inflammation. Roflumilast and other phosphodiesterase 4 inhibitors have been shown to provide additive protection in asthma when added to corticosteroid and anti-leukotriene treatment. Developmental drugs with dual phosphodiesterase 3 and 4 inhibition are thought to be able to provide bronchodilation and anti-inflammatory activities and will consequently be pushed forward in their clinical development for the treatment of asthma and COPD.

KEYWORDS:

• Roflumilast
• PDE4 inhibition
• asthma
• chronic obstructive lung disease

Article highlights

• Most therapies developed for the treatment of asthma have focused on inhibiting T2 inflammation and eosinophilic disease; however, it is well established that some patients with asthma exhibit a neutrophilic airway inflammatory profile.

• Many of the inflammatory cells and structural cells that participate in disease pathogenesis in human airways express PDE4.

• Roflumilast is a PDE4 inhibitor that has been shown to improve forced expiratory flow in 1 s, forced vital capacity, peak expiratory flow, and reduce rescue medication use in patients with asthma.

• In human models of asthma, roflumilast has been reported to reduce airway inflammation, inhibit allergen-induced airway hyperresponsiveness, and allergen- and exercise-induced bronchoconstriction.

• Roflumilast added to maintenance therapy such as inhaled corticosteroids, antileukotrienes, and beta-agonists was shown to be effective in patients with asthma and COPD.

• Roflumilast is currently not approved for the treatment of asthma but has been approved in many countries for the treatment of severe COPD.

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Declaration of interest

G Gauvreau has received research support in the form of grants from Altana AG. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.