Tapering from high-dose inhaled corticosteroids possible in most asthma patients treated with benralizumab

Up to 92% of patients with eosinophilic asthma who are effectively managed on benralizumab can successfully be tapered from high-dose (HD) inhaled corticosteroids/formoterol (ICS/F) within 32 weeks. Maintenance of the achieved lowered ICS dose was possible until week 48 in nearly 96% of participants.

“We’ve known for a long time now that HD ICS is associated with significant adverse effects,” Prof. David J. Jackson (King's College London, UK) stated. He pointed out that the Global Initiative for Asthma (GINA) recommends reducing HD ICS for asthma patients who are on biologics. “Unusually for GINA, this recommendation is not based on any evidence whatsoever, because the SHAMAL trial (NCT04159519) is the first study that has been done prospectively, to assess whether this is safe and possible,” Prof. Jackson further underlined.

SHAMAL is an open-label, active-controlled, phase 4 open study that investigated the possibility of a successful HD ICS reduction in patients with severe eosinophilic asthma, well-controlled with add-on benralizumab [1]. In total, 168 adults were randomised 1:3 to either continuation of their benralizumab dose at 30 mg every 8 weeks plus HD ICS/F as before or tapering of HD ICS/F from medium to low dose and further down to maintenance of anti-inflammatory reliever (AIR). The primary endpoint was defined as the proportion of patients reducing HD ICS/F to medium or low dose or the as-needed regimen only at the end of the initial period over 32 weeks.

The overall baseline parameters of the participants showed a mean age of 57.7 years, 53% were women, a mean fractional exhaled nitric oxide (FeNO) of 27.0 ppb, a mean Asthma Control Questionnaire (ACQ)-5 score of 0.53, and 2.9 exacerbations within the last year before starting benralizumab.

At week 32, nearly all participants (92%) were able to successfully reduce HD ICS/F, with 15% tapering to medium dose, 17% to low dose, and 61% to AIR only. This corresponds to an overall 73% lesser mean daily dose of HD ICS/F in the tapering arm (see Figure). Furthermore, 95.8% of the participants were able to maintain their reduced doses to week 48. Among the participants who reduced their medication to AIR, changes in lung function measured by forced expiratory volume in 1 second (FEV₁) and FeNO revealed a significant correlation, indicating a decline in FEV₁ and an increase in FeNO from baseline (P=0.0003 at week 32 and P=0.0241 at week 48). “Interestingly, this was not seen with exacerbations,” Prof. Jackson informed, revealing that almost all the participants remained completely exacerbation-free, as only 8% had 1 exacerbation over the study year. These results were also mirrored by the absence of a clinically meaningful decrease in symptom control in the ACQ-5.

“Most patients with severe eosinophilic asthma adequately controlled on benralizumab and background therapy can reduce ICS/formoterol dose from high dose, whilst maintaining asthma control,” Prof. Jackson concluded.

Figure: Development of change in mean total ICS per day over time [1]

1. Jackson D. SHAMAL: reduction of maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab: a randomised phase 4 study. Abstract 798, ERS International Congress 2023, 9–13 September, Milan, Italy.

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Posted on 29 October 202329 October 2023