Doxycycline fails to effectively reduce exacerbation rate in COPD patients

Chronic obstructive pulmonary disease (COPD) exacerbations are worsening or "lare up" of COPD symptoms. An exacerbation is caused by an infection in the lungs, but in some cases, the cause is unknown. Long-term macrolide treatment is said to be effective at reducing exacerbations but there is a paucity of evidence for other antibiotic classes like doxycycline.

A recent study in American Journal of Respiration and Critical Care reveals that doxycycline wasn’t effective in reducing exacerbation rate, over 12-months, in participants with COPD, in those who exacerbated regularly, but was beneficial in those with more severe COPD or blood eosinophil counts less than 300 cells/μL.

James P Allinson and team recruited people with moderate to very severe COPD and an exacerbation history from 3 UK centres and randomised to 12-months doxycycline 100mg once daily or placebo. The primary study outcome was exacerbation rate per person year.

The key findings of the study are

• A total of 222 people were randomised. Baseline mean FEV1 was 1.35 (SD 0.35) L; 52.5 (SD 15.9) % predicted. Median number of treated exacerbations in the year before the study was 2 (1-4).

• 71% of patients reported ≥2 exacerbations. 81% were already prescribed inhaled corticosteroids at baseline.

• COPD exacerbation rate did not differ between the groups - doxycycline/placebo rate ratio 0.86 (0.67, 1.10); p=0.23.

• No difference was seen if only treated exacerbations or hospitalisations were considered. In pre-planned sub-group analysis, doxycycline appeared to better reduce the exacerbation rate among people with severe COPD (RR:0.36 (0.15, 0.85); p=0.019), and in those with an eosinophil count <300 cells/μL (RR:0.50 (0.29, 0.84); p=0.01).

• Health status measured by SGRQ was 5.2 points worse in the doxycycline group at 12-months (p<0.007).

Allinson and team concluded that “Doxycycline did not significantly reduce exacerbation rate, over 12-months, in participants with COPD, who exacerbated regularly, but may have benefitted those with more severe COPD or blood eosinophil counts <300 cells/μL.”

Reference: Allinson JP, Vlies BH, Brill SE, Law M, Burnside G, Finney LJ, Alves-Moreira L, Donaldson GC, Calverley PMA, Walker PP, Wedzicha JA. A Double-Blind, Randomised, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable COPD. Am J Respir Crit Care Med. 2023 Jul 14. doi: 10.1164/rccm.202212-2287OC.