Simplified, tailored treatment for asthma improves patient outcomes

Asthma is a highly prevalent disease that can affect anybody regardless of age, race, and location. The overall burden of asthma remains severe. Despite the range of available therapies and well-established guidelines, there remains a significant unmet need in the management of asthma. [BMC Public Health 2012;12:860; Respir Res 2023;24:169; Eur Respir J 2014;43:343-373]

“Outcomes from asthma treatment remain relatively poor,” said Professor John Blakey from Sir Charles Gairdner Hospital, Nedlands, Perth, Australia, during a symposium at APSR 2023. “More than half of patients with asthma across the globe have poor symptomatic control of their disease.” [Med J Aust 2015;202:492-496]

No one-size-fits-all treatment

“We must acknowledge that asthma is not a specific disease,” said Blakey. “It is an umbrella term for a heterogenous syndrome and there is no one-size-fits-all treatment. Individuals with asthma have varying amounts of the different components of the disease,” Blakey said. [Lancet 2017;391:e2-e3]

Mucus hypersecretion, airway inflammation, and airway hyperreactivity are three of its components. Blakey said it is important for clinicians to identify the specific component that mainly triggers patients’ asthma symptoms, and tailor treatments to their specific needs.

“Sometimes, the wrong tools are used,” he pointed out. A clinician may have a perfectly good drug, but if used in a patient who lacks the component that the drug should be targeting, the benefit goes down the drain. This is also a waste of resources, he explained.

“Perhaps, this is why many patients remain symptomatic despite being prescribed an inhaled corticosteroid and a long-acting beta2-adrenergic agonist (ICS-LABA),” Blakey said.

The role of add-on LAMA in asthma

The Global INitiative for Asthma (GINA) guidelines recommend the use of a long-acting muscarinic antagonist (LAMA) for moderate-to-severe asthma that is uncontrolled on ICS-LABA. [ginasthma.org/gina-reports, accessed November 23, 2023]

LAMAs work by reducing bronchoconstriction and mucus secretion. [Expert Opin Investig Drugs 2017;26:761-766; Eur Respir J 2018;52:1701247; Drugs 2016;76:999-1013] With these mechanisms of action, clinicians would expect to see improvements in their patients’ bronchodilation with LAMAs, as well as better lung function test, Blakey said.

In patients with poorly controlled asthma despite the use of inhaled glucocorticoids and LABAs, the addition of a LAMA significantly increased the time to the first severe exacerbation and provided modest sustained bronchodilation. The mean change in the peak FEV₁ from baseline was significantly greater with the addition of a LAMA than with placebo, so was the predose (trough) FEV_1. [N Engl J Med 2012;367:1198-1207]

“It was also reassuring to see the same kind of benefit in trough FEV₁ and adverse event profile in a Japanese study,” added Blakey. [PLoS One 2015;10:e0124109]

How does add-on therapy fare in the real world?

Unfortunately, the uptake of add-on asthma therapy remains very low. “In the real world, only about 2 percent of asthma patients are on LAMAs, biologics, etc … A lot of patients are on as-needed salbutamol on its own,” Blakey shared. [Respir Med 2021;186:106524]

The question is – why have we not seen a huge uptake in the utilization of add-on therapy, which has been shown to be helpful in asthma?

“If I suggest an extra inhaler to my patients, they will have questions about how much extra hassle would it be for them, how much would it cost them, and how much extra benefit they could get from it. With the extra inhaler, patients are more likely to make technical errors. They are also less likely to use inhalers on a regular basis. An extra device would also cost them more. And with only modest improvements in exacerbation rates, we have to be aware that this is not something that patients would see as a priority,” Blakey explained in detail.

Benefits of once-daily triple therapy in a single-inhaler for asthma

This is where an ICS/LAMA/LABA combination therapy delivered via a single inhaler for asthma may come in handy. Previous studies have shown that the benefits from adding a LAMA to a combination are comparable to using a separate LAMA inhaler. These findings were extended by the phase IIIA CAPTAIN* study. In this large trial, researchers compared the effects of once-daily single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) with FF/VI in 2,436 adult patients with inadequately controlled asthma (Asthma Control Questionnaire-6 [ACQ-6] score of ≥1.5) on ICS-LABA. The patients were recruited from 416 hospitals and primary care centres across 15 countries. [Lancet Respir Med 2021;9:69-84]

“Results showed there were statistically significant improvements in lung function and trough FEV₁ with FF/UMEC/VI vs FF/VI after 24 weeks of treatment across all comparisons**,” reported Blakey. “There were also modest improvements in exacerbations.”

In these patients with uncontrolled moderate or severe asthma on ICS-LABA, single-inhaler FF/UMEC/VI appears an effective treatment option, with a favourable risk-benefit profile. Higher-dose FF primarily reduced the rate of exacerbations, particularly in patients with raised biomarkers of type 2 inflammation.

“To simplify: A higher-dose steroid meant better protection against asthma attacks, while more bronchodilators meant better lung function,” explained Blakey. “In patients having exacerbations particularly driven by eosinophilic inflammation, we should [consider] giving a higher-dose steroid. In those with poor lung function or greater airway hyperreactivity, we should give them more bronchodilators,” he continued.

Overall, the CAPTAIN study showed how a simplified, once-daily dosing regimen with single-inhaler FF/UMEC/VI – with doses that can be tailored to meet individual patient needs – achieved better asthma control and lung function improvement.

Environmental implications

Blakey said it is also important to reduce waste from the use of extra inhalers. Identifying the right treatment for the right patient simplifies treatment, which would also consequently help address this environmental concern.

“The carbon footprint of exacerbation from asthma is huge. We can reduce this by getting the diagnosis right and matching the most appropriate medicines and non-pharmacological treatments to the patients’ needs. This will subsequently benefit healthcare systems moving forward,” he added.

Take-home message

Blakey said it is important to match the right treatment to the right patient. “Some patients will need a higher-dose ICS but may not need very extensive bronchodilator therapy. Some might require a lower-dose ICS but may need dual bronchodilation to achieve the best results.”

“We can do better for our patients in a number of ways. When available, single-inhaler [FF/UMEC/VI] therapy is certainly one of those ways in which we can promote better adherence and nudge people towards better asthma outcomes,” he concluded.