Blood eosinophil-guided prednisolone therapy for COPD exacerbations

By Rebecca Jenkins

Blood eosinophil­-guided oral prednisolone therapy for an acute COPD exacerbation is noninferior to standard care and can safely reduce systemic glucocorticoid use, a UK primary care­-based trial suggests.

The multicentre, double­-blind, randomised, placebo­-controlled Studying Acute Exacerbations and Response (STARR2) study was conducted in 14 UK general practices using point­-of­-care blood eosinophil count testing to guide prednisolone use in patients with a COPD exacerbation.

Of the 308 adults with diagnosed COPD recruited to the study, 93 were randomly assigned on exacerbation to blood eosinophil­ directed treatment (BET) or to standard care treatment (ST), the researchers wrote in The Lancet Respiratory Medicine.

At the time of randomisation, participants in the BET group received oral prednisolone 30mg once daily for 14 days if their blood eosinophil count was high (≥2%), or a matched placebo if it was low (<2%).

Meanwhile, participants in the ST group received oral predniso­ lone 30mg once daily irrespective of their blood eosinophil count. Both groups also received a short course of oral doxycycline.

Participants were current or former smokers (mean age 70 years and mean percent predicted FEV1 60.9%) with a history of at least one exacerbation in the previous 12 months requiring systemic corticosteroids with or without antibiotics.

The primary outcome, based on unique exacerbation episodes, was the proportion of treatment failure (defined as exacerbations needing retreatment, hospital admission or death) at 30 days.

The researchers noted that a significant randomisation error occurred at the beginning of the study and led to it being converted from a superiority trial to a noninferiority trial.

In a modified intention­-to­-treat analysis, BET was not inferior to ST treatment, researchers reported, with a large nonsignificant estimated effect in reducing treatment failures after a COPD exacerbation between BET and ST (relative risk 0.60).

Professor Christine McDonald, Director of Respiratory Medicine at Austin Health in Victoria, said that in addition to the error at randomisation, there were a few caveats with the study design, including that researchers had used a 14­-day course of prednisolone, whereas current guidelines advocated a shorter five­-day course.

‘Nevertheless, this is an important trial demonstrating that higher eosinophil counts can assist in the choice of therapy for acute exacerbation,’ she told Medicine Today.

Professor McDonald said there was a tendency to use a ‘blunderbuss approach’ to treating COPD exacerbations, with many patients receiving high­-dose, short­-acting beta­-agonists/ short-acting muscarinic antagonists plus corticosteroids and antibiotics.

In addition, corticosteroids continued to be used much more in respiratory medicine compared with other fields where alternative therapies had been introduced.

‘We do not yet have reliable alternative therapies, but it is pleasing to know from this study that, if eosinophil counts are not high, we can probably safely leave off the oral prednisolone,’ she said.

Lancet Respir Med 2023; doi: https://doi.org/10.1016/S2213-2600(23)00339-9.