A long-term prophylactic dose of doxycycline 100 mg daily in patients with moderate chronic obstructive pulmonary disease (COPD) did not significantly reduce the overall exacerbation frequency, according to study results published in the American Journal of Respiratory and Critical Care Medicine.
Researchers sought to assess the efficacy of long-term prophylactic doxycycline in reducing the rate of exacerbations in patients with COPD over 12 months.
The researchers conducted a double-blind, randomized, placebo-controlled trial of 222 outpatients at 3 centers in the United Kingdom who had COPD categorized as grade 2 to 4 (moderate to very severe COPD) by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). All study participants were aged 45 years and older, had a history of smoking 10 cigarette packs a year, and had previously received treatment with antibiotics and/or corticosteroids for at least 1 COPD exacerbation in the past 12 months. Participants (mean age, 67 years; 57% male; 34% smokers) were randomly assigned to receive a daily 100 mg dose of doxycycline (n=110) or placebo (n=112) for 12 months.
Patient medical history, post-bronchodilator spirometry measurements, c-reactive protein, and blood eosinophil count was recorded at study enrollment. Patients were also tasked to complete 2 respiratory health status questionnaires — the St. George’s Respiratory Questionnaire (SGRQ) and the COPD Assessment Tool (CAT) — both upon enrollment and at the end of the trial. In addition, patients completed daily symptom diary cards to record exacerbations, treatments, and adverse events; these diary cards were reviewed by researchers every 3 months until the end of the trial at month 12.
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Prophylactic doxycycline did not significantly reduce exacerbation rate, over 12-months, in participants with COPD, who exacerbated regularly. However, the impact of long-term doxycycline varied according to baseline blood eosinophil count.
Exacerbation onset was identified based on participant symptom diary information as well as by the need for hospitalization or treatment with antibiotics or steroids. Based on symptom diary information, exacerbation onset was defined as a developing or worsening of at least 2 symptoms (including at least 1 major symptom) that lasted for at least 2 days. Major symptoms included dyspnea, increased sputum volume, and purulence; minor symptoms were classified as sore throat, cold, fever, cough, wheezing, and chest tightness.
A negative binomial regression model was used to calculate the difference in exacerbation rate between the doxycycline group and placebo group. SGRQ scores were used to measure change in respiratory health status from the beginning to the end of the trial.
In comparing exacerbation rates, researchers found an insignificant difference between the overall median rate for the doxycycline group vs the placebo group (2.28 exacerbations per person-year vs 3.35 exacerbations per person-year, respectively; P =.23). There was also an insignificant difference in the median rate of treated exacerbations per person year between the doxycycline and placebo groups (1.27 vs 2.01, respectively; P =.34). Adjustments for baseline smoking status, exacerbation rate during the previous year, sex, SGRQ, lung function, and oxygen saturations at baseline did not affect these findings.
In respect to respiratory health status, the SGRQ score did not change in the doxycycline group, but significantly improved in the placebo group, from 1.44 to 9, at the 12-month review (P =.007). Notably, the occurrence of dyspepsia, nausea, and vomiting was higher in the doxycycline group and the placebo group experienced more infections and nervous system disorders.
Subgroup analysis found that prophylactic doxycycline significantly reduced the exacerbation rate in patients with severe COPD (risk ratio [RR], 0.36; 95% CI, 0.15 to 0.85; P =.019) and in patients with an eosinophil count less than 300 cells/uL (RR, 0.50; P =.01).
Study limitations include the lack of statistical significance of many findings and the lack of detailed surveillance of patients’ antibiotic resistance.
“Prophylactic doxycycline did not significantly reduce exacerbation rate, over 12-months, in participants with COPD, who exacerbated regularly. However, the impact of long-term doxycycline varied according to baseline blood eosinophil count,” the study authors concluded. Prophylactic doxycycline “may prove more effective for those with a lower baseline eosinophil rate or severe disease,” said the researchers.
