medwireNews: Treating chronic obstructive pulmonary disease (COPD) exacerbations with prednisolone according to blood eosinophil count does not lead to increased treatment failures or worsening lung function or symptoms relative to the current standard of treating all patients, show results from the STARR2 trial.
“We believe that the current paradigm of treating all COPD exacerbations with systemic glucocorticoids is thus out of date, and we now have further evidence that supports that current clinical practice should change,” write Mona Bafadhel (King’s College London, UK) and co-authors in The Lancet Respiratory Medicine.
They explain that international guidelines already recommend using peripheral blood eosinophil count to predict response to inhaled glucocorticoids for COPD maintenance treatment. Bafadhel and team hypothesized that they could also use this biomarker to direct oral prednisolone therapy at the time of a COPD exacerbation.
To test their hypothesis, they recruited 308 adults (aged ≥40 years) with COPD, from 14 primary care practices, who had at least a 10 pack–year smoking history and a history of at least one exacerbation requiring systemic corticosteroids with or without antibiotics in the previous 12 months. Of these, 156 did not have an exacerbation and 152 were put forward for randomization.
However, an error in the randomization procedure was detected partway through the trial and 59 patients were excluded as a result, leaving 93 (mean age 70 years, 56% men, mean percentage of predicted forced expiratory volume in 1 second [FEV1] 60.9%,) available for inclusion in the modified intention-to-treat analysis.
Of these, 47 participants were randomly allocated to receive blood eosinophil-directed treatment (BET), which comprised oral prednisolone 30 mg once daily for 14 days if their eosinophil count was high (≥2%) on a point-of-care test at randomization or placebo if it was low (<2%). The remaining 46 patients were given standard care with prednisolone 30 mg once daily for 14 days irrespective of their eosinophil result. All patients also received antibiotics and were eligible for re-randomization at further exacerbations (with a maximum of four exacerbations per participant).
The researchers report that prednisolone was prescribed in 66% of 73 exacerbations in the BET group and in all 71 exacerbations in the standard care group.
The treatment failure rate at 30 days post-exacerbation was lower in the BET group than in the standard care group, at 19% versus 32%, with failure defined as retreatment with antibiotics or steroids, hospitalization for any cause, or death.
Bafadhel et al say that the difference between the two groups met the criteria for the noninferiority of BET relative to standard care but the reduced statistical power that resulted from the randomization error and removal of participants meant they were unable to demonstrate superiority.
Among the secondary outcomes measured, there was no significant difference between the two groups in the improvement of post-bronchodilator FEV1, health-related quality of life (QoL), or respiratory symptoms at day 14. However, QoL at day 30, measured using the COPD Assessment Test, was significantly better in the BET group than in the standard care group.
The authors say that “[t]he number of adverse events in the study was low and similar between both study arms,” with two cases of glycosuria and two hospitalizations for COPD exacerbation reported in the BET group and one case of each in the standard care group.
Bafadhel and team conclude that “blood eosinophil count identifies patients who would benefit from systemic glucocorticoids and helps reduce the systemic exposure and toxicity of universal prednisolone therapy.”
They add: “[T]he widespread use of COPD rescue packs containing prednisolone, self-initiated by patients at the onset of an exacerbation, might be driving increased harm,” and suggest that healthcare systems should “encourage systematic assessment of COPD exacerbations to provide patients with the right therapy in a precision biomarker-directed way.”
In an accompanying comment, Alejandro Comellas and Spyridon Fortis, both from the University of Iowa in Iowa City, USA, congratulate Bafadhel et al on their study “and for providing important information that could radically improve clinical practice.”
They believe that “[t]his report advances the field of precision medicine in COPD,” and that “[b]lood eosinophil counts should be considered as a component of point-of-care testing to guide systemic glucocorticoids in acute COPD exacerbation.”
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Lancet Respir Med 2023; doi:10.1016/ S2213-2600(23)00298-9
Lancet Respir Med 2023; doi:10.1016/S2213-2600(23)00339-9