During acute COPD exacerbations, use of blood eosinophil-directed prednisolone therapy is noninferior to standard care and can be used to safely reduce systemic glucocorticoid use in low eosinophil exacerbations, according to study findings published in The Lancet Respiratory Medicine.
Clinical practice has not yet incorporated use of blood eosinophil biomarker-directed therapy for acute exacerbation of COPD. Researchers therefore assessed whether eosinophil biomarker-directed oral prednisolone could effectively treat acute exacerbation of COPD and could safely reduce systemic corticosteroid use. Treatment failure (ie, the need for re-treatment with antibiotics or steroids, any-cause hospitalization, or death as of 30 days after the exacerbation in the modified intention-to-treat population) was the primary study endpoint.
Researchers in the United Kingdom conducted the STARR2 study (ClinicalTrials.gov Identifier: NCT04458636), a randomized, double-blind, placebo-controlled trial, from November 2017 through April 2020, at 14 primary care practices. A total of 308 adult participants at least 40 years of age were recruited for the study. All participants currently or formerly smoked (at least 10 pack-year smoking history) and were diagnosed with COPD (defined as post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio <0.7, plus at least 1 exacerbation requiring systemic corticosteroids with or without antibiotics within the previous year).
Participants were randomly assigned 1:1 to standard treatment (ST; prednisolone 30 mg daily regardless of the point-of-care eosinophil count) or to blood eosinophil-directed treatment (BET; oral prednisolone 30 mg daily with eosinophil count of at least 2%, or placebo with eosinophil count of less than 2%) for 14 days. All patients received antibiotics. Re-randomization was possible (for a maximum of 4 times per participant) with further exacerbations.
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Blood eosinophil-directed prednisolone therapy at the time of an acute exacerbation of COPD is non-inferior to standard care and can be used to safely reduce systemic glucocorticoid use in clinical practice.
Participants in the BET vs ST group included more individuals who currently smoked (34% vs 15%) and fewer who formerly smoked (66% vs 85%). Comorbidities were similar between groups (98% of each group overall with any), most commonly hypertension, reflux, and depression for both groups.
In the modified intention-to-treat analysis, a total of 144 exacerbations were experienced by 93 participants (mean [range] age, 70 [46-84] years; 44% women; mean percent predicted FEV1 [SD], 60.9% [19.4]). Of those exacerbations, 73 were experienced by patients in the BET group (n=47) and 71 exacerbations were experienced by patients in the ST group (n=46). At 30 days post-exacerbation, the researchers found 19% treatment failures (14/73) in the BET group, and 32% treatment failures (23/71) in the ST group.
A nonsignificant estimated effect reducing treatment failures after a COPD exacerbation was noted between the BET and ST groups (risk ratio, 0.60; 95% CI, 0.33-1.04; P =.07). The researchers found the study groups had a similar low frequency of adverse events, most commonly glycosuria (2% BET group; 1% ST group) and hospital admission for COPD exacerbation (2% BET group; 1% ST group). No deaths were reported in the study.
Significant study limitations include an error in the randomization code that reduced the statistical power below what was needed to complete the current investigation as a superiority study.
“Blood eosinophil-directed prednisolone therapy at the time of an acute exacerbation of COPD is non-inferior to standard care and can be used to safely reduce systemic glucocorticoid use in clinical practice,” the research authors concluded. The researchers added, “Biomarker-based subgroup analysis also showed that the greatest benefit in lung function and COPD specific quality life was in participants with a high eosinophil count receiving prednisolone.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
