Delivering monoclonal antibodies via inhalation: a systematic review of clinical trials in asthma and COPD

ABSTRACT

Introduction

Advances in understanding the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD) led to investigation of biologic drugs targeting specific inflammatory pathways. No biologics are licensed for COPD while all the approved monoclonal antibodies (mAbs) for severe asthma treatment are systemically administered. Systemic administration is associated with low target tissue exposure and risk of systemic adverse events. Thus, delivering mAbs via inhalation may be an attractive approach for asthma and COPD treatment due to direct targeting of the airways.

Areas covered

This systematic review of randomized control trials (RCTs) evaluated the potential role of delivering mAbs via inhalation in asthma and COPD treatment. Five RCTs were deemed eligible for a qualitative analysis.

Expert opinion

Compared to systemic administration, delivering mAbs via inhalation is associated with rapid onset of action, greater efficacy at lower doses, minimal systemic exposure, and lower risk of adverse events. Although some of the inhaled mAbs included in this study showed a certain level of efficacy and safety in asthmatic patients, delivering mAbs via inhalation is still challenging and controversial. Further adequately powered and well-designed RCTs are needed to assess the potential role of inhaled mAbs in the treatment of asthma and COPD.

KEYWORDS:

• Asthma
• COPD
• inhaled
• monoclonal antibodies
• systematic review

Article highlights

• Monoclonal antibodies (mAbs) are innovative drugs targeting specific inflammatory pathways.

• To date, mAbs are indicated as add-on therapy in patients with severe asthma while no biologic drugs are licensed for the treatment of chronic obstructive pulmonary disease (COPD).

• Systemic administration of mAbs is associated with low target tissue exposure and risk of systemic adverse events.

• Delivering mAbs via inhalation is characterized by rapid onset of action, greater efficacy at lower doses, minimal systemic exposure, and lower risk of adverse events.

• Further adequately powered and well-designed randomized control trials (RCTs) are needed to assess the potential role of inhaled mAbs in the treatment of asthma and COPD.

Declaration of interest

P Rogliani discloses a relationship with Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma, Novartis. M Cazzola discloses a relationship with Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Lallemand, Mundipharma, Novartis, Pfizer, Verona Pharma, and Zambon. L Calzetta is discloses a relationship with Boehringer Ingelheim, Novartis, AstraZeneca, Chiesi Farmaceutici, Almirall, ABC Farmaceutici, Edmond Pharma, Zambon, Verona Pharma, and Ockham Biotech. 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 paper was not funded.