Benralizumab helps maintain severe asthma control with reduced ICS doses

Treatment with benralizumab allows tapering of inhaled corticosteroid (ICS) doses for patients with severe eosinophilic asthma, without compromising disease control and increasing exacerbations, as shown in the results of the phase IV SHAMAL study.

In a cohort of patients who were adequately controlled on benralizumab and high-dose ICS/formoterol, 92 percent were able to reduce their ICS/formoterol dose by week 32, reported lead study author Dr David Jackson of King’s College London, London, UK. [Jackson D J, et al, ERS Congress 2023]

“Most of them, about two-thirds approximately, could get all the way down to anti-inflammatory reliever [as needed] (61 percent). Only a very small number had to stop at medium dose (15 percent),” Jackson added.

During the subsequent 16-week maintenance period, 95.8 percent of patients were able to maintain at the reduced ICS/formoterol dose for up to week 48. Some 1.7 percent of patients had a further dose reduction, while 2.5 percent had a dose increase.

Jackson noted that despite the reduced ICS/formoterol doses, most patients (92.0 percent) remained completely free of exacerbations. Only 8.0 percent of patients had one exacerbation over the year of the study.

At the same time, there were no meaningful changes in symptom control, as reflected by a very tiny increase in ACQ-5* score from baseline to week 48 (0.2, with the minimally clinically important difference being 0.5).

Rise in nitric oxide levels

“What SHAMAL fundamentally demonstrates is that you can safely reduce from high-dose down to low-dose [ICS] without lung function decline. This is a massive win for patients, because all the side effects are really at the high dose,” Jackson said.

However, he noted that some patients who came all the way down to anti-inflammatory reliever had decreased forced expiratory volume (FEV1), which could indicate lung function decline, and this was associated with increased levels of fractional exhaled nitric oxide (FeNO).

During a Q&A session, discussant Prof Dave Sing of University of Manchester, Manchester, UK, referred to an earlier study showing that when patients with moderate-to-severe asthma had better lung function at baseline and had lower doses of ICS, the presence of high nitric oxide levels were associated with greater loss of lung function. Sing asked Jackson what his approach would be for patients who have high FeNO and may be at risk of lung function decline even when treated with benralizumab and having no exacerbations.

Jackson advocated the use of FeNO for all patients with severe asthma, saying that FeNO gives valuable information that is distinct from symptoms and exacerbations.

“What do I do in clinic is I use FeNO routinely to make sure that we are not putting our patients at greater risk of airway remodelling, lung function decline, and IL-13 mechanisms that FeNO fundamentally relates to. And you monitor lung function,” Jackson said.

“The key thing is getting the high dose down to a safer lower dose, which now has been shown to be safe with benralizumab,” he added.

Study details

SHAMAL included 168 adult patients (mean age 57.7 years, 19.65 percent women, 75.0 percent White, 37.5 percent former smoker) with severe eosinophilic asthma who had received at least three consecutive benralizumab doses (30 mg injection Q8W) and who were on current maintenance treatment with a high-dose ICS/formoterol.

At baseline, mean prebronchodilator FEV1 was 2.27 L, mean FeNO level was 2.27 ppb, mean ACQ-5 score was 0.53, and mean number of exacerbations in 12 months prior to benralizumab was 2.9.

Of the patients, 43 were assigned to receive stable ICS/formoterol dosing (400/12 µg x2 BID plus short-acting beta agonist [SABA] reliever as needed) while 168 were assigned to ICS/formoterol taper (medium dose: 200/6 µg x2 BID plus reliever as needed; low dose: 200/6 µg x1 BID plus reliever as needed; ICS/formoterol reliever: as needed only) for 32 weeks. All patients entered a 16-week maintenance period thereafter.

*5-item Asthma Control Questionnaire