Eosinophil-guided therapy noninferior to standard treatment for COPD exacerbations

DALLAS — Patients with acute exacerbations of chronic obstructive pulmonary disease requiring hospitalization who received eosinophil-guided corticosteroid therapy fared as well as patients who received standard care, according to the CORTICO-COP study.

The findings were presented at the American Thoracic Society International Conference and simultaneously published in The Lancet Respiratory Medicine.

In the intention-to-treat analysis, the primary outcome of days alive and out of hospital within 14 days of enrollment did not differ between patients randomly assigned eosinophil-guided therapy (n = 159) compared with control therapy (n = 159; mean, 8.9 vs. 9.3 days; P = .34).

At 30 days, no significant differences emerged between the eosinophil-guided therapy and control arms in treatment failure, defined as recurrence of acute exacerbation resulting in ED visits, hospital admission or intensification of pharmacological treatment (P = .9). Additionally, rates of acute COPD exacerbations or death were 24.5% and 17% (P = .1) and the rates of death were 6% and 4% (P = .43), respectively.

Additional outcomes

However, the study results did show significant differences corticosteroid treatment between the eosinophil-guided therapy and control arms. Specifically, the length of treatment with systemic corticosteroids was shorter and the mean cumulative systemic corticosteroid dose on day 5 was lower in patients assigned eosinophil-guided therapy vs. control therapy (P < .0001 for both). Notably, the difference in mean cumulative corticosteroid dose persisted from days 30 to 90.

Also, at 30 days, no instances of new-onset diabetes occurred, but more patients in the control arm experienced worsening of diabetes control (66.6% vs. 8.3%; P = .0001).

After 90 days, there were no significant differences between the eosinophil-guided therapy and control arms in infections requiring antibiotic treatment (34.6% vs. 42.8%; P = .13) or in dyspepsia, ulcer complications or initiation of new proton-pump inhibitor therapy.

Mean changes from baseline in forced expiratory volume in 1 second, COPD assessment scores, BMI and Medical Research Council dyspnea grades also did not differ between study arms at any time point.

“Eosinophil-guided corticosteroid treatment is a new, safe treatment for severe COPD exacerbations that leads to a reduction in systemic corticosteroids, is noninferior to standard treatment, is associated with better diabetes control and is easy to implement,” Pradeesh Sivapalan, MD, from the department of internal medicine and respiratory medicine at Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, said during a presentation of the data at the ATS International Conference.

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He added, however, that the long-term outcomes need to be analyzed.

A step forward

The multicenter, randomized, controlled, open-label, noninferiority trial was conducted at three university-affiliated hospitals in Denmark. Patients were enrolled within 24 hours of hospital admission at the participating sites. All were aged at least 40 years and had known airflow limitation and a diagnosis of COPD verified by a specialist.

On the first day, all patients received 80 mg of IV methylprednisolone and patients in the eosinophil-guided therapy arm received 37.5 mg of oral prednisolone tablets daily for up to 4 days only on days when their blood eosinophil count was at least 300 cells/µL, whereas patients in the control arm received 37.5 mg of oral prednisolone daily for the following 4 days.

The study, despite its strengths, was not without limitations, Takudzwa Mkorombindo, MD, and Mark Dransfield, MD, both from the division of pulmonary, allergy and critical care, Lung Health Center, University of Alabama at Birmingham, wrote in a linked comment in The Lancet Respiratory Medicine.

For instance, the study’s open-label design may have led to bias or co-interventions by the treating team, according to the editorial authors. The findings are also not generalizable because the researchers excluded patients with very severe exacerbations requiring invasive ventilations or ICU admission. Finally, the optimal cutoff of peripheral blood eosinophil count is uncertain “and some might argue that measurement of blood eosinophils, which only partly reflect lung pathology, is too blunt an instrument to select therapy,” according to Mkorombindo and Dransfield.

“Although Sivapalan and colleagues’ study does not answer all the questions about the predictive role of blood eosinophils in acute COPD exacerbations, and perhaps an eosinophil-guided approach is not yet ready for routine clinical use, it is clearly a step in the right direction and points towards a precision approach to a problem we currently treat near uniformly,” Mkorombindo and Dransfield wrote. – by Melissa Foster

References:

Sivapalan P. Late-Breaking Clinical Trials. Presented at: American Thoracic Society International Conference; May 17-22, 2019; Dallas.

Mkorombindo T, et al. Lancet Respir Med. 2019;doi:10.1016/S2213-2600(19)30179-1.

Sivapalan P, et al. Lancet Respir Med. 2019;doi:10.1016/S2213-2600(19)30176-6.

Disclosures: Sivapalan reports he has received personal fees from Novartis. Dransfield reports he has received grants from the U.S. National Department of Defense, NIH and the American Lung Association; personal fees from Genentech, Mereo and Quark Pharmaceuticals; personal or other fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and PneumRx/BTG; and other fees from Boston Scientific, Pulmonx and Yungin. Mkorombindo reports no relevant financial disclosures.