Current long-acting muscarinic antagonists for the treatment of asthma

ABSTRACT

Introduction

The role of long-acting muscarinic antagonists (LAMAs) is well established in uncontrolled asthma, but not in milder stages.

Areas covered

This review examines the main randomized controlled trials (RCTs) that have investigated LAMAs administered as monotherapy or in combination to asthmatic patients, according to the different phenotypes. It offers an overview of the role of LAMAs or their fixed dose combinations (FDCs) in the treatment across all the different stages of asthma.

Expert opinion

Tiotropium is now widely recognized as treatment for moderate to severe uncontrolled asthma (step 4–5) in adults and children. The most recent new evidence is: a) in adults, three different LAMA/long-acting β₂-agonist (LABA)/inhaled corticosteroid (ICS) FDCs have been recently approved, extending the treatment options for these patients; b) therapy with LAMAs does not depend on patient’s Th2 status and justifies the indication regardless of patient’s phenotyping; c) in the milder stages, the high variability of response to LAMAs and the lack of a good phenotyping of patients represents the main obstacle in prescribing LAMAs. A better characterization of parasympathetic tone activity could improve LAMAs prescription.

KEYWORDS:

• Long-acting muscarinic antagonist
• LAMA
• asthma
• tiotropium bromide
• umeclidinium bromide
• glycopyrronium bromide
• triple therapy

Article highlights

• In asthma that is poorly controlled by ICS/LABA combination, LAMAs are a highly effective adjunctive therapy

• Tiotropium is recommended as add-on therapy in severe uncontrolled children and adults asthmatics (steps 4–5)

• Three different triple therapies in FDC will soon be available for adult patients with severe symptomatic asthma

• LAMAs in monotherapy in mild-moderate asthma is not yet well defined, because contrasting results come from RCTs

• In milder stages, a better phenotyping of asthmatic patients is essential in prescribing LAMAs and most likely to target the therapy to subjects with an increased cholinergic tone

• LAMAs can be useful in some specific group of patients such as asthmatics with fixed obstruction, or smokers or elderlies.

• In asthma, there are no concerns about the safety of LAMAs.

Abbreviations

Ach: Acetylcholine; ACQ-7: Asthma Control Questionnaire −7; AQLQ: Asthma Quality of Life Questionnaire; AE: Adverse effect; ASM: Airway smooth muscle; BDP: Beclomethasone Dipropionate; BUD: Budesonide; COPD: Chronic obstructive pulmonary disease; DPI: dry powder inhaler; DXF: Doxofylline; FDA: Food and Drug Administration; FeNO: Fractional Exhaled Nitric Oxygen; FEV₁: Forced Expiratory Volume in 1 second; FVC: Forced Vital Capacity; FF: Fluticasone Furoate; FP: Fluticasone propionate; FORM: Formoterol; GINA: Global Initiative for Asthma; GLY: Glycopyrronium bromide; HH: HandiHaler; ICS: Inhaled Corticosteroid; IND: Indacaterol; LABA: Long-Acting β2 adrenoceptor agonist; LAMA: Long-Acting muscarinic antagonist; MM: Mometasone Furoate; pMDI: pressurized Metered Dose Inhaler; PEF: Peak Expiratory Flow; RCT: Randomized Controlled Trial; RR: Relative Risk; TIO: Tiotropium bromide; UMEC: Umeclidinium bromide; VI: Vilanterol.

Declaration of interest

J Ora reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Novartis, and Zambon. P Rogliani has received grant support and personal fees from Boehringer Ingelheim, Chiesi Farmaceutici, and Almirall. She has also received personal fees from AstraZeneca, Biofutura, GlaxoSmithKline, Menarini, and Mundipharma and grant support from Zambon. L'Calzetta, meanwhile, has received grant support and personal fees from Boehringer Ingelheim, Novartis, and Zambon. L Calzetta has also received non-financial support from AstraZeneca as well as grant support from Chiesi Farmaceutici and Almirall and personal fees from ABC Farmaceutici, Edmond Pharma, Verona Pharma, and Ockham Biotech. MG Matera meanwhile reports receiving personal fees from Boehringer Ingelheim, AstraZeneca, Chiesi Farmaceutici, Almirall, ABC Farmaceutici, and GlaxoSmithKline. She has also received grants and personal fees from Novartis. 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.