GINA 2019: A paradigm shift

Dr Dermot Nolan provides an overview of the latest asthma treatment and management options,  focusing on the new 2019 GINA guidelines

Asthma remains a significant disease in Ireland with over 450,000 patients, and the fourth highest rate of asthma prevalence in the world. Despite advances in both understanding and in new medications, it continues to have a significant burden on the overall well-being of patients. We have about 70 patients dying every year with asthma and over 5,000 patients admitted to hospital every year with asthma. This, however, hides the real morbidity, with asthma control remaining poor for the majority of patients. This causes children to be unable to partake in sport and adults to miss school and life events due to uncontrolled asthma. Doctors and carers often underestimate the effect that asthma has on patients, as it may be asked in a short way, such as ‘how is your asthma?’, to which patients may reply, ‘fine’ or ‘good’, despite having many symptoms which they may feel is part of the normal asthma experience.

Patients and indeed many doctors are shocked to hear that one salbutamol (short-acting beta agonist, SABA) canister contains 200 puffs of the drug and that this should last patients at least a year with well-controlled asthma, in which they use it less than twice per week.

There has been some concern about overuse of SABA inhalers for some time, in that whilst they do give immediate bronchodilator relief, they fail to address the underlying pathophysiology, which is an inflammatory process.

Is this the end of the blue inhaler on its own?

The new GINA (Global Initiative for Asthma) 2019 guidelines have just been published and represent a significant change for the management of asthma in adolescents and adults. It recommends for the first time that SABAs (ie, salbutamol) should no longer be used alone for the treatment of asthma. GINA recommends that all adults and adolescents with asthma should receive ICS (inhaled corticosteroids)- containing controller medications to reduce their risk of serious exacerbations and to control symptoms. This has been included in the NICE guidelines in the UK in their last asthma guideline. This will have repercussions in Ireland where salbutamol alone remains in the top-10 drugs prescribed in the country and where over-reliance on salbutamol is commonplace.

The new guidelines represent the culmination of a 12-year campaign by GINA to obtain evidence for new strategies for the treatment of mild asthma.

Their aims were to:

1. Reduce risk of asthma-related exacerbations and death, including in patients with so-called ‘mild’ asthma.

2. To provide a consistent message about the aims of treatment, including prevention of exacerbations across the spectrum of asthma severity.

3. To avoid a pattern of patient over-reliance on SABA early in the course of the disease.

Why are there concerns about SABA-only treatment?

Many guidelines over the past 50 years have recommended SABA as the first line to treat asthma and to move on to ICS when that proved to be unsuccessful in controlling symptoms. Early on in asthma, it was felt that the disease was one principally of bronchoconstriction, however, we now know that it is principally a disease of inflammation, even in those with infrequent or intermittent symptoms. Although SABA provides a quick relief of symptoms, it is associated with increased risk of exacerbations and lower lung function. Regular use increases allergic responses and airway inflammation. Over-use of SABA (eg, >three canisters dispensed in a year) is associated with risk of severe exacerbations and dispensing >12 canisters per year is associated with increased risk of asthma deaths.

Starting asthma treatment

For the best outcomes, ICS-containing treatment should be initiated as soon as possible after the diagnosis has been made because:

Patients with mild asthma can have severe exacerbations.

Low-dose ICS reduces risk of hospitalisation and death.

Low-dose ICS is effective at preventing exacerbations, improving lung function and preventing exercise-induced bronchoconstriction, even in patients with mild asthma.

Early treatment with ICS leads to better lung function than if symptoms have been present for more than two-to-four years.

In occupational asthma, early removal from the trigger factors at work are the key element in improving the situation.

Most patients with asthma do not need more than low-dose ICS, because most of the benefit is achieved at low-dose treatment.

For most patients a controller can be started with either as-needed ICS-formoterol (or if not available, low-dose ICS whenever SABA is taken) or with regular low-dose ICS.

Step 1

This step was SABA when needed in previous guidelines. This is now only recommended for patients with symptoms less than twice a month and no exacerbations. The new guidelines recommend as-needed low-dose ICS-formoterol.

The factors that influenced this decision were:

These patients can have severe exacerbations despite minimal interval symptoms.

Use of ICS-formoterol was associated with reduced exacerbations and 20 per cent reduction in ICS use as opposed to regular low-dose ICS.

To reduce conflicting messages in the past where patients were told to use their SABA medication as much as they needed and then being told that they needed to reduce SABA use to gain control.

ICS adherence in patients is poor and exposes patients to risks of SABA use only.

All studies so far have been with budesonide-formoterol but beclomethasone-formoterol may also be suitable.

This new guideline will have implications for all clinicians treating asthma, as it is no longer recommended to start with a SABA-only treatment. It will therefore be important to make an accurate diagnosis and it is estimated that up to 30 per cent of patients with GP diagnoses of asthma may not in fact have asthma. This is due to lack of resourcing of accurate diagnostics in many cases.

Formoterol is the recommended as-needed medication due to its faster onset of action (equivalent to SABAs) as opposed to salmeterol.

However, the cost of the ICS-formoterol medications may be a barrier for some patients and will raise the cost of inhalers for the vast majority of asthma patients and the State, which funds the majority of the treatments. Further studies may be needed on this in countries with different healthcare structures and costs. There are studies showing that it is cost-effective in reducing the costs of exacerbations and hospitalisations.

GPs and practice nurses will have to ensure the correct technique is used for the new inhalers.

The key element of assess, adjust and review remain in place when dealing with patients with asthma.

Assessing:

Confirming the diagnosis.

Symptom control.

Comorbidities.

Inhaler technique and adherence.

Patient goals.

Adjusting:

Treatment of modifiable risk factors and comorbidities.

Non-pharmacological strategies.

Education and skills training.

Reviewing:

Symptoms.

Exacerbations.

Side-effects.

Lung function.

Patient satisfaction.

The use of tiotropium was in the last guidelines at Step 4, for patients over the age of 12 years with exacerbations, but the age of this has been reduced down to patients aged over six years in line with manufacturers’ licencing policy.

The use of sublingual immunotherapy (SLIT) has been kept in the guidelines at Step 3 for patients who are allergic to house dust mites (proven on skin prick test or SpIGe testing) who are aged over 12 years with exacerbations.

In summary

The new guidelines are an important step to try to reduce the burden of asthma but will present challenges to doctors to alter older prescribing patterns, to patients who have to adapt to a different management approach and to funders who may expect to see an initial rise in cost of medications. One would expect savings to be made with less secondary care costs and less indirect costs, such as time off work. The new guidelines need to be considered at national level before widespread adoption.

See www.ginaasthma.org for more information.