Biomarker-directed prednisolone matches up to standard care for COPD exacerbations

Testing for eosinophils during chronic obstructive pulmonary disease (COPD) flare-ups to guide prednisolone treatment compares favourably with standard of care, with no increase in treatment failures, symptoms, or lung function decline, according to data from the phase III STARR2 trial.

“Systemic glucocorticoids, such as prednisolone, are the mainstay of treatment for exacerbations of COPD, with a number needed to treat of 10 to reduce one treatment failure. This universally applied treatment has been given on the basis of the short-term effect of systemic glucocorticoids on reduced length of hospital stay, despite more patients being harmed than not, and with worrisome effects of prednisolone on morbidity and mortality,” the investigators said.

“We believe that the current paradigm of treating all COPD exacerbations with systemic glucocorticoids is thus out of date, and we now have further evidence that supports that current clinical practice should change,” they added.

Noninferior

In STARR2, the primary endpoint of treatment failure at 30 days after a COPD exacerbation occurred less frequently in the group of patients who received blood eosinophil-directed treatment (BET) than in the group of those who received standard care treatment (19 percent vs 32 percent; relative risk [RR], 0.60, 95 percent confidence interval [CI], 0.33–1.04; p=0.070), establishing the noninferiority of BET in reducing treatment failures. [Lancet Respir Med 2024;12:67-77]

The modified intention-to-treat analysis included data on 144 exacerbation events from 93 patients (mean age 70 years, 56 percent men, mean percent predicted FEV₁ 60.9 percent). Fifty-four of the patients had only one exacerbation, while 29, nine, and one patient had two, three, and four exacerbations, respectively.

Of the 93 patients, 47 received BET (prednisolone 30 mg once daily if eosinophil count was high [≥2 percent] or placebo if eosinophil count was low [<2 percent]) and 46 received standard care treatment (prednisolone 30 mg once daily irrespective of the point-of-care eosinophil result). More than half of the patients (58 percent) were already being treated with inhaled glucocorticoids at baseline, and three-fourths were former smokers (75 percent) with a mean smoking history of 55 pack years. 

“We were able to demonstrate that there was a reduction in prednisolone prescriptions and a lower cumulative dose of prednisolone in the BET group compared with the ST group,” the investigators said.

There was a 33-percent reduction in prednisolone prescribing in the BET group than in the standard care group. When additional doses of prednisolone prescribed to patients who had treatment failure and those who had additional retreatment in the 30 days after randomization were evaluated, the cumulative treatment failure prednisolone dose was 1,620 mg in the BET group as opposed to 3,450 mg in the standard care group, respectively.

“Finally, we have shown that in patients with exacerbations and low eosinophil count there was no significant difference in treatment failures nor resolution of symptoms or lung function whether treated with prednisolone or placebo,” the investigators pointed out.

At day 14, the improvements observed in postbronchodilator FEV₁, health-related quality of life (COPD Assessment Test), or respiratory symptoms (visual analogue scale) were comparable between the BET and standard care groups, despite 30 percent of the patients in the BET group being treated with placebo for their exacerbation.

In terms of safety, the frequency of adverse events was similar between the BET and standard care groups. The most common adverse events in both groups were glycosuria (2 percent vs 1 percent) and hospital admission for COPD exacerbation (2 percent vs 1 percent). None of the patients died during the study period.

Outdated practice

“Unlike other medical disciplines, the field of respiratory medicine has not achieved meaningful reductions in the use of systemic glucocorticoids, increasing the risk to patients of severe life-limiting side-effects and comorbidities. Notably, primary care physicians and pulmonologists now account for the majority of prednisolone prescriptions in the UK,” the investigators pointed out. [Eur J Endocrinol 2019;181:267-273; BMJ 2017;357:j1415; Thorax 2021;76:A21-A]

It is also worth noting that the current guidelines are based on trials involving fewer than 1,000 patients, which predate the widespread availability and use of inhaled dual bronchodilators and glucocorticoids in COPD, they added. [https://goldcopd.org/wp-content/uploads/2019/12/GOLD-2020-FINAL-ver1.2-03Dec19_WMV.pdf]

Based on the results of STARR2, the investigators stressed that the treatment of COPD exacerbations should be guided by a blood eosinophil biomarker. Blood eosinophil counts identify patients responsive to systemic glucocorticoids in COPD exacerbations, allowing for reduced overall steroid exposure.

“This study also suggests that the widespread use of COPD rescue packs containing prednisolone, self-initiated by patients at the onset of an exacerbation, might be driving increased harm. Health systems need to encourage systematic assessment of COPD exacerbations to provide patients with the right therapy in a precision biomarker-directed way,” they added.