Anti-IL-5 agents go head-to-head in Australian severe asthma trial

Dr John Politis

The anti-IL-5 agents mepolizumab and benralizumab produce substantial improvements in severe asthma after six months,  with benralizumab providing greater improvements in some outcomes, a Victorian trial has shown.

Conducted in two severe asthma clinics in Melbourne, the trial involved 184 patients with asthma that was not controlled despite optimum used of inhaled asthma therapies, with frequent exacerbation requiring steroids and around 40% of patients requiring oral steroid maintenance therapy.

In findings presented at the TSANZ-SRS 2022 virtual meeting, Dr John Politis, an advanced trainee in respiratory and sleep medicine at Monash Lung and Sleep, described how the therapies were selected at physician discretion. Mepolizumab patients had slightly worse asthma control at baseline, likely reflecting the fact that the drug had been available for longer resulting in self selection for more severe asthma. However this initial difference was adjusted for in subsequent analyses.

At six months after starting treatment with an anti-IL-5 agent, both groups of patients showed substantial and similar improvements in asthma as measured by 2.3 unit falls in Asthma Control Questionnaire scores. No further improvements were seen when treatment were maintained at 12 months.

However in terms of lung function, the benralizumab group showed greater improvement than mepolizumab at six months 0.258 vs 0.085L, and a significant difference of 150ml was still seen between groups after adjusting for baseline severity.

The benralizumab group also showed further improvement at 12 months, whereas the mepolizumab group did not.

For steroid-treated exacerbations, both groups showed substantial falls at six months, from 2.42 to 0.9 for mepolizumab and from 2.95 to o.48 for benralizumab (incident reduction ratio 0.49 for benralizumab). Both agents also produced significant reductions of at least 80% in ED presentations for asthma.

The reduction in blood eosinophil counts was also significantly greater for benralizumab over mepolizumab at six and 12 months.

Dr Politis said the improvements in severe asthma achieved at six months and maintained at 12 months with both agents were substantial and represented clinically relevant benefits.

The greater improvements seen with benralizumab might reflect the difference in mode of action between the two anti-IL-5 agents, he suggested.

He noted that benralizumab acted directly on the IL-5 receptor on the eosinophil to block cytokine formation and induce cell apoptosis, whereas mepolizumab binds to circulating IL-5 and inactivates it.

“A physician might be left asking whether there is anything to choose between these two effective treatments or whether they were essentially equivalent,” he said.

“There are no direct head-to-head trial to provide guidance, however the data from this study suggests that benralizumab may be substantially more effective at reducing exacerbations by a factor of half compared to mepolizumab, and substantially more effective at improving lung function.,” he concluded.

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