Unmet needs in severe asthma

Unmet needs in the management of patients with asthma 

Asthma affects approximately 339 million people worldwide,³ of whom ~5–10% have severe or uncontrolled asthma.⁴ 

Severe asthma is defined by the Global Initiative for Asthma (GINA) as asthma that remains uncontrolled despite adherence to optimised high-dose inhaled corticosteroids (ICS) and long-acting β₂-agonist (LABA) therapy and the treatment of contributory factors, or asthma that worsens when high-dose therapy is decreased.²  

The long-term goals of severe asthma management include achieving good symptom control and minimising the future risk of exacerbations and disease progression (eg, decline of lung function and persistent airflow limitation).² In many cases where patients have poor symptom control and/or exacerbations despite medium- or high-dose ICS and LABA therapy, their asthma may appear difficult to treat because of contributory factors, such as incorrect inhaler technique, poor adherence, smoking or comorbidities, or because of incorrect diagnosis.² For these patients, GINA recommends assessment of these contributory factors and consideration of an add-on therapy, eg, a long-acting muscarinic antagonist (LAMA).² If problems persist, referral to a specialist centre for phenotypic assessment and consideration for add-on biologic targeted treatments are recommended.²  

Confirming the diagnosis of asthma, assessing contributory factors and optimising treatment strategy are the key steps for consideration in the diagnosis and management of severe asthma.²  

To date, there has been great progress in the diagnosis and management of severe asthma,^5,6 with biologics representing a major advancement in the treatment landscape.⁷ However, many patients with severe asthma are poorly controlled.  

A recent study found that approximately 60% of patients with severe asthma remained suboptimally controlled despite treatment with standard-of-care medications.⁸ This significant finding was described following a retrospective and prospective analysis of the International Severe Asthma Registry – a data set of 4990 patients receiving GINA Step 5 treatment or with severe asthma remaining uncontrolled at GINA Step 4 (December 2014 to December 2017). Poorly controlled asthma was defined in this study according to Asthma Control Test (score 5–15; ‘very poorly controlled’) or Asthma Control Questionnaire (score >1.5; ‘poorly controlled’) categorisations.⁸  

What is the impact of poorly controlled severe asthma for patients?

Below is an example of a typical patient with severe asthma. Despite adherence to daily ICS-LABA treatment, he continues to experience symptoms that hinder his daily life and remains susceptible to severe exacerbations.  

Suboptimal asthma control can have a significant impact on patient outcomes: 

• Exacerbations potentially leading to hospitalisation occur in 12–27% of patients with severe asthma in a year^8–10 
• Increased risk of comorbidities and systemic side effects (eg, pneumonia, osteoporosis and type 2 diabetes) associated with frequent bursts of oral corticosteroids^11,12 
• Poor quality of life (eg, activity limitation)¹³ 
• Increased risk of mortality¹⁴ 

• Healthcare costs associated with severe uncontrolled asthma are 3× higher than costs for patients with severe controlled disease¹⁵ 

What challenges are associated with existing treatments for poorly controlled asthma? 

Oral corticosteroids (OCS) are the primary therapy for resolution of acute exacerbations.¹⁶ However, patients with severe asthma are often exposed to multiple courses of OCS,¹⁷ and cumulative and chronic exposure is associated with an increased risk of side effects.^12,18,19 As little as 0.5–1 g (or up to four short courses) of OCS can cause serious adverse effects, including cataracts, pneumonia, type 2 diabetes, cardiovascular disease, renal impairment and osteoporosis.¹²  

Globally, 20–60% of patients with severe or uncontrolled asthma have received long-term OCS.¹⁸ The annual cost of OCS-related adverse events per person with severe asthma is estimated to be €1958, in Italy.¹⁹  

As such, there is a clear need to avoid maintenance OCS treatment where other options are available (in line with updated recommendations by GINA)² and to continue to develop and identify alternative steroid-sparing treatments for asthma exacerbations and for patients with severe asthma.¹² 

Asthma is heterogeneous; patients often show activation of multiple innate and adaptive inflammatory pathways:^20,21 This contributes to a significant unmet need in the management of severe uncontrolled asthma.² Targeting specific steps of the immune-inflammatory cascade through highly selective biologic therapies offers the potential of achieving optimal disease control in several severe asthma inflammatory phenotypes.¹  

However, major unmet needs persist owing to lack of access and inadequate response to or ineligibility for currently available biologic treatments.¹  

Indeed, 72% of patients with asthma in primary care in the UK, who are thought to have severe asthma, have never been referred to a specialist.²² Globally, approximately 75% of patients with poorly controlled severe asthma (GINA Step 4/5) are not receiving biologics.⁸