Anti‐Inflammatory Dose Doxycycline (40 mg Controlled‐Release) Confers Maximum Anti‐Inflammatory Efficacy in Rosacea

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Abstract
Background. Two large clinical trials have recently demonstrated the efficacy of a 40‐mg controlled‐release formulation of doxycycline in the treatment of rosacea, a dose well below the conventional level of 100 to 200 mg/d. Since no formal dose‐response studies have been conducted, the authors analyzed phase 3 data to determine whether a dose‐efficacy relationship exists. Methods. Standard parametric regression analyses were used to estimate the correlations between dose (mg/kg body weight) and overall drug exposure (area under the curve [AUC]) in a phase 1 pharmacokinetic study and between dose and efficacy (mean change from baseline in total inflammatory lesion count at week 16) in 2 pooled phase 3 clinical efficacy studies. Additional regressions were run at each visit for the clinical efficacy studies to determine whether results differed across visits. A regression analysis was also performed in a subset of patients who showed a greater efficacy response. Results. We found overall drug exposure (AUC) to have a highly significant correlation with dose (mg/kg) (r=0.49; P=.006). In contrast, clinical efficacy did not correlate with dose at any of the visits at week 3 (r=0.01; P=.85), week 6 (r=0.04; P=.53), week 12 (r P=.98), and week 16 (r=0.03; P=.64) or among the subset of patients who showed greater clinical benefit. Conclusions. Higher mg/kg doses led to higher plasma concentrations but did not lead to increased clinical efficacy. Anti‐inflammatory dose doxycycline (40‐mg controlled‐release formulation) conferred peak anti‐inflammatory efficacy in the treatment of rosacea. (SKINmed. 2007;6:221–226)