Conference Coverage

Biomarker-guided steroid therapy shown safe for COPD



Eosinophil-guided corticosteroid therapy for patients with chronic obstructive pulmonary disease (COPD) is equivalent in efficacy to standard of care therapy, but the eosinophil-guided therapy may help mitigate the harmful side effects associated with even short courses of corticosteroids, investigators said in a primary care–based randomized trial.

Among patients in 14 primary care practices in the United Kingdom who experienced COPD exacerbations, the proportion of patients who experienced treatment failure at day 28 was 27% for those who were randomized to receive prednisolone only when blood eosinophil counts on a point-of-care assay equaled or exceeded 2%, compared with 34% of all patients randomized to standard of care.

The relative risk for treatment failure using the eosinophil-guided approach was 0.82, which did not reach statistical significance, but indicated noninferiority for the biomarker-based dosing method, Mona Bafadhel, MD, of King’s College London, reported on behalf of colleagues in the Stratified Treatment to Reduce Risk in COPD (STARR2) trial.

“The STARR2 trial showed that eosinophil-guided prescription in primary care is safe and is not associated with worsening outcomes. This is the largest primary care multicenter trial, and probably adds another 20% to the literature base for exacerbations in COPD,” she said in an oral abstract presentation at the European Respiratory Society 2022 Congress.

“A personalized endotype-based treatment with oral prednisolone is possible in patients with COPD and I think should be now part of clinical guidelines,” she added.

Too much of a good thing

Although systemic corticosteroids are the universal treatment for COPD exacerbations, the drugs are also known to increase harm, with studies showing that cumulative doses of oral corticosteroids in COPD patients is associated with an increased risk for death. In addition, systemic corticosteroids are the third most common cause of adverse events leading to hospitalization, behind only chemotherapy and antibiotic use leading to Clostridioides difficile infections, Dr. Bafadhel said.

“And of course, corticosteroids are associated with significant harmful effects, including a five-times increased risk of sepsis, three-times increased risk of [venous thromboembolism], and a twice-increased risk of fracture,” she said.

Dr. Bafadhel and colleagues had previously shown in the single-center BEAT-COPD study that peripheral blood eosinophils at the time of a moderate COPD exacerbation could be used to safely direct oral corticosteroid therapy. She also pointed to a 2019 multicenter open-label study showing that eosinophil-guided care was noninferior to standard prescribing of oral corticosteroids for patients with severe exacerbations.

Primary care study

The investigators conducted the current study to test whether eosinophil-guided therapy at the point of care in a primary practice setting was efficacious, with the ultimate goal of encouraging changes in guidelines.

They recruited patients with COPD exacerbations from 14 general practices in Oxfordshire and Buckinghamshire in the Thames Valley.

The patients were randomly assigned to receive either standard of care or the biomarker-guided intervention for 14 days. In this arm, patients with eosinophil counts of 2% or greater received matched prednisolone, while patients with counts below 2% received placebo. The patients were blinded to the assigned drug.

A total of 203 exacerbations among 152 patients were evenly allocated to treatment or control groups. The mean patient age was 71. Of the 102 exacerbations allocated to eosinophil-guided therapy, 34 were treated with placebo.

As noted before, in the intention-to-treat analysis the primary outcome of the treatment failure rate, defined as any need for antibiotics and/or steroids at one month, was 27% in the biomarker-guided arm and 34% in the standard care arm.

“In the per-protocol analysis we also demonstrated that there was a suggestion that there is possible superiority of using blood eosinophil-directed oral corticosteroid prescriptions at the time of acute exacerbation using the point-of-care eosinophil test,” Dr. Bafadhel said.

There were no significant differences in the secondary outcomes of mean change in forced expiratory volume in 1 second (FEV1), COPD Assessment Test scores from exacerbation to follow-up, and symptoms according to a visual analog scale.

Invited discussant Dave Singh, MD, of the University of Manchester, England, asked Dr. Bafadhel how the data she presented supported her conclusions about the potential benefits of eosinophil-guided therapy, given that the P values were nonsignificant.

“The primary outcome was powered on noninferiority, and of course what we’ve shown is that it’s not any worse, it’s not any better, but of course it’s the effect of how many courses of steroids you can reduce in that population,” Dr. Bafadhel replied.

She noted that although the investigators have not performed an economic analysis to determine how many adverse events might be avoided using the biomarker-guided approach, “we do know that some of these patients who are given prednisolone, their comorbidities of diabetes worsened, for example.”

In the online Q&A for the presentation, Sohail Ansari, MD, from the Mid and South Essex NHS Foundation Trust in the United Kingdom, said that many patients in primary care practices receive “rescue packs” containing antibiotics and steroids, but may not be equipped to know when they should use the steroids and therefore may overuse them.

“Perhaps community-based, adequately resourced respiratory teams [may] be a way forward, but it will need adequate investment and commitment,” he wrote.

The trial was supported by the University of Oxford and National Institute for Health and Care Research, UK. Dr. Bafadhel reported grant and research support from the National Institute for Health and Care Research, Asthma & Lung UK, AstraZeneca, and Roche, and honoraria or fees from others. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Ansari reported no conflicts of interest.

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