Switching biologics in severe asthma: pragmatic approach needed

Switching biologic agents in adults with severe asthma is likely to benefit some patients who do not respond to the initial agent, but there is little evidence to guide decision making in this area, Australian clinicians say.

About one in ten patients switch biologic therapies but questions remain about a number of issues related to switching, according to a paper published by Dr John Politis and Professor Philip Bardin of Monash Health, Melbourne.

More information is needed about the optimum duration of initial therapy before considering a switch, and the merits of switching to an agent targeting an alternative disease pathway, the authors write in the Annal of the American Thoracic Society (link).

They note that about half of patients with severe asthma have the T2 inflammatory phenotype that may be targeted by biologics such as omalizumab (via IgE), mepolizumab/reslizumab/benralizumab (via IL-5 or IL-5R) and dupilumab (via IL4/IL13R).

These agents have been shown in randomised trials to reduce exacerbation rates and oral steroid doses, improve symptom control and increased lung function.

However there have been no randomised head-to-head trials that would provide robust evidence to inform switching between different agents and therefore clinicians must look to the limited information provided by observational studies, the authors say.

In their paper they summarise the findings from four studies that investigated switching between agents that target a different pathway.

Studies such as the OSMO trial showed significant benefits after switching from omalizumab to mepolizumab such as improvements in symptom control, reductions in exacerbations and hospital admission rates and improvements in pre-bronchodilator.

However some of the studies were limited by relatively short duration of follow up of up to nine months.

A further two observational studies provided useful information on improvements in severe asthma control after switching between biologic agents that target the same pathway, such as  mepolizumab to benralizumab.

Other ‘real world’ observational  studies had provided useful information on the duration of initial therapy with a biologic before switching due to sub-optimal response. The mean time to initial switch varied from as little as four months months to  up to nine months.

These studies also shed some light on the patterns of biologic switching, with the most common first switch being from omalizumab to an anti-IL5/5R agent (50%), but these observations “may not reflect recent trends due to the availability of newer agents,” the authors noted.

With little likelihood of prospective head-to-head randomised trials in this area, they said the best evidence on biologic switching is likely to come from well-designed observational studies that gather important information such as factors affecting choice and duration of initial therapy, criteria for treatment failure and confounding factors such as adherence to other treatments.

“In summary, switching biological agents in adults with severe asthma is likely to benefit some patients,” they conclude.

“For now, drawing on real-life observational data combined with ‘bespoke’ implementation may be a pragmatic approach to guide choice of an alternative biological agent.”

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