Long-term inflammatory rosacea management with subantibiotic dose oral doxycycline 40 mg modified-release capsules once daily

Abstract

An important goal of effective rosacea treatment is to maximize the duration of remission. This was a two-part study. Part 1 was a multicenter, open-label, 12-week study in which adults with moderate or severe inflammatory lesions (papules and pustules) of rosacea received subantibiotic dose oral doxycycline 40 mg modified release (SDD40 ) and topical metronidazole gel 1%. Part 2 was a multicenter, randomized, double-blind, placebo-controlled, 40-week study in which successfully treated subjects received once-daily SDD40 or placebo capsules. The primary objective was to assess relapse and efficacy during long-term use of SDD40 versus placebo. Relapse was defined as a return to baseline investigator global assessment (IGA) or lesion count, or any other necessary change in treatment. Part 1 enrolled 235 subjects. Sixty-five subjects in the SDD40 treatment group and 65 subjects in the placebo group met the definition of treatment success at week 12, and were included in the Part 2 analysis. At the end of Part 2, half as many subjects in the SDD40 group had relapsed compared to the placebo group (13.8% [n = 9] vs. 27.7% [n = 18], p < 0.05). Significant differences in the median change in inflammatory lesion counts were also observed (p < 0.05). Adverse events (AEs) were generally mild-moderate in severity, and most were not treatment-related. Stinging/burning responded with more improvement in subjects treated with SDD40 . After 52 weeks of once-daily treatment, subantibiotic dose doxycycline significantly reduced the relapse rate and inflammatory lesion counts in subjects with moderate-to-severe inflammatory rosacea.

Keywords: metronidazole 1%; moderate or severe inflammatory lesions of rosacea; randomized controlled trial; remission; subantibiotic dose doxycycline.

Conflict of interest statement

Sam Brantman, PharmD is an employee of Galderma Laboratories.

© 2021 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC.

Figures

FIGURE 1

Study design and subject disposition

FIGURE 2

Subject photographs of treatment success and long‐term management of inflammatory lesions of rosacea with subantibiotic dose oral doxycycline 40 mg. Subject pictured is a 43 year‐old male with severe inflammatory rosacea at baseline (A), successfully treated with topical metronidazole 1% and subantibiotic dose oral doxycycline, and assessed to have an IGA score of 0 (clear) at the week 12 visit (B). The subject was then randomized to receive subantibiotic dose oral doxycycline for an additional 40 weeks of treatment. The subject completed the 40‐week long‐term management part without relapse and was assessed to have an IGA score of 1 (near clear) at the final study visit (C)

FIGURE 3

End of study lesion counts in treatment and placebo groups correlate with week 12 IGA. The end of study inflammatory lesion counts of subjects in the subantibiotic dose doxycycline and placebo treatment groups were analyzed according to their IGA scores at the part 1 week 12 assessment (0 [clear], 1 [near clear], and 2 [mild]). After 40 weeks of treatment, subjects who entered part 2 with an IGA score of 2 (mild) maintained a significantly lower number of inflammatory lesions in the subantibiotic dose doxycycline group, when compared with the placebo treatment group (p = # [r = 0.3])

FIGURE 4

Rate of relapse during part 2: (A) Relapsed subjects over time (ITT) and (B) relapsed subjects at study end