Long-term doxycycline may reduce exacerbations for some COPD patients

A randomized trial in the U.K. found that 12 months of doxycycline did not improve chronic obstructive pulmonary disease (COPD) exacerbations overall versus placebo but may have reduced rates in patients with severe disease or lower blood eosinophil counts.

Patients with severe chronic obstructive pulmonary disease (COPD) and those with blood eosinophil counts below 300 cells/μL may benefit from long-term doxycycline therapy, a recent study found.

Researchers in the United Kingdom performed a randomized trial to determine whether 12 months of doxycycline therapy reduced the rate of exacerbations in COPD. Patients with moderate to very severe COPD and a history of exacerbations were randomly assigned to receive 100 mg of doxycycline once daily or placebo for 12 months. Exacerbation rate per person-year was the primary study outcome. The results were published by the American Journal of Respiratory and Critical Care Medicine on July 14.

One hundred ten patients were assigned to receive doxycycline, and 112 were assigned to receive placebo. The mean age was 67 years, 57% were male, and 34% currently smoked. The mean FEV1 at baseline was 1.35 L (SD, 0.53), or 52.5% (SD, 15.9%) of predicted. Patients reported a median of two treated exacerbations in the year before the study, with 71% reporting two or more. Eighty-one percent of patients were already prescribed inhaled corticosteroids at baseline. At study enrollment, 27% of patients had a blood eosinophil count of 300 cells/μL or greater and 73% had a count below 300 cells/μL.

Among the 183 patients who completed the study, no statistically significant difference in overall COPD exacerbation rate was seen between groups, with a median of 2.28 events per person-year (interquartile range [IQR], 1.03 to 4.68) with doxycycline and 3.35 events per person-year (IQR, 1.03 to 5.68) with placebo. The unadjusted negative binomial rate ratio was 0.86 (95% CI, 0.67 to 1.10; P=0.23). The results did not differ when only treated exacerbations or hospitalizations were considered. A preplanned subgroup analysis found that doxycycline appeared to have a larger effect on exacerbation rate in patients with severe COPD (relative risk, 0.36 [95% CI, 0.15 to 0.85]; P=0.019) and in those with an eosinophil count below 300 cells/μL (relative risk, 0.50 [95% CI, 0.29 to 0.84]; P=0.01). Overall adverse events did not differ substantially between groups, although GI events were more common with doxycycline than with placebo. Patients in the doxycycline group had worse health status at 12 months, as measured by the St. George's Respiratory Questionnaire (P<0.007).

The researchers noted that they were unable to evaluate risk of antibiotic resistance and that most patients were already taking inhaled corticosteroids and bronchodilators at baseline. They concluded that long-term doxycycline therapy did not significantly reduce exacerbation rate overall in patients with COPD but may have some benefit in those with more severe disease or blood eosinophil counts below 300 cells/μL. “Future studies are needed to confirm whether the potentially substantial effect of doxycycline on exacerbation numbers is present in patients prospectively identified as having a blood eosinophil count below 300 cells/μL,” the researchers wrote.