Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial.

BACKGROUND: Patients with rosacea have increased amounts of cathelicidin and protease activity but their usefulness as disease biomarkers is unclear. OBJECTIVE: We sought to evaluate the effect of doxycycline treatment on cathelicidin expression, protease activity, and clinical response in rosacea. METHODS: In all, 170 adults with papulopustular rosacea were treated for 12 weeks with doxycycline 40-mg modified-release capsules or placebo in a multicenter, randomized, double-blind, placebo-controlled study. Clinical response was compared with cathelicidin and protease activity in stratum corneum samples obtained by tape strip and in skin biopsy specimens obtained from a random subset of patients. RESULTS: Treatment with doxycycline significantly reduced inflammatory lesions and improved investigator global assessment scores compared with placebo. Cathelicidin expression and protein levels decreased over the course of 12 weeks in patients treated with doxycycline. Low levels of protease activity and cathelicidin expression at 12 weeks correlated with treatment success. Low protease activity at baseline was a predictor of clinical response in the doxycycline treatment group. LIMITATIONS: Healthy control subjects were not studied. CONCLUSIONS: Improved clinical outcome correlated with reduced cathelicidin and protease activity, supporting both the mechanism of doxycycline and the potential of these molecules as biomarkers for rosacea.

Effectiveness and safety of once-daily doxycycline capsules as monotherapy in patients with rosacea: an analysis by Fitzpatrick skin type.

Rosacea is often under-recognized or misdiagnosed in patients with skin of color (Fitzpatrick Skin Types [FST] IV-VI). Subtle clinical features and a low index of suspicion likely contribute to less frequent diagnosis in this population. Clinical trials of therapeutic agents for rosacea generally include few patients from nonwhite racial/ethnic groups and therefore, potential differences in treatment outcomes have not been previously studied. The objective of this prospective analysis was to fill the gap in knowledge of the effectiveness and safety of treatment for rosacea in patients with skin of color. We analyzed data from 826 adults aged ≥ 18 years with papulopustular (subtype 2) rosacea (663 FST I-III; 163 FST IV-VI). All patients received doxycycline 40 mg capsules (30 mg immediate release and 10 mg delayed release beads) once daily as monotherapy for 12 weeks in this open-label, multicenter, community-based study. Investigators assessed disease severity with the Investigator's Global Assessment (IGA) and erythema with the Clinician's Erythema Assessment (CEA). Significant improvement in disease severity and erythema was obtained in patients with FST I-III and IV-VI at week 12 (P<.001). Treatment success, defined as an IGA score of 0 or 1 was achieved in 74.6% and 74.3% of patients with FST I-III and IV-VI, respectively. Approximately 12% of patients experienced adverse events with no difference between the two skin type groups. The results of this prospective subgroup analysis of data from a large community-based trial suggest that doxycycline produced similar effectiveness and safety profiles in patients with FST I-III and IV-VI.

Effectiveness and safety of modified-release doxycycline capsules once daily for papulopustular rosacea monotherapy results from a large community-based trial in subgroups based on gender.

This article is a prospective planned analysis of data evaluating the effectiveness and safety of modified-release doxycycline capsules (30 mg immediate-release and 10 mg delayed-release beads) used once daily for up to 12 weeks in subgroups of males and females with papulopustular (subtype 2) rosacea from a large, open-label, multicenter, community-based study. A total of 1421 patients participated in the study. The per-protocol population comprised 826 patients on monotherapy, with 28.5% male participants (n=235) and 71.5% female participants (n=591). Rosacea was assessed on a 5-point investigator's global assessment (IGA) scale (0=clear, 1=near clear, 2=mild, 3=moderate, 4=severe). Erythema was also assessed on a 5-point clinician's erythema assessment (CEA) scale (0=none, 1=mild, 2=moderate, 3=significant, 4=severe). At baseline, males had a higher percentage of IGA scores of 3 (116 per 235; 49.4% versus 273 per 591; 46.2% in females) and 4 (32 per 235; 13.6% versus 35 per 591; 5.9% in females). Significant improvements in severity rating and erythema were observed in males and females as demonstrated by shifts in the distribution of IGA and CEA scores between baseline and week 12 (P<.001). Treatment success (IGA score of 0 or 1) at week 12 was achieved in 172 per 235 (73.2%) of males and in 444 per 591 (75.2%) of females. Adverse events (primarily mild or moderate gastrointestinal events) were reported in 9.9% of males and 12.8% of females. Anti-inflammatory dose doxycycline, which is administered as a 40 mg modified-release capsule once daily was effective and safe as monotherapy for papulopustular rosacea in both the female (n=591) and male (n=235) study groups. This specific 40 mg capsule delivers 30 mg immediate-release and 10 mg as delayed release using specially designed beads, and is subantimicrobial with both single and repeated dosing.

The appearance of facial foundation cosmetics applied after metronidazole gel 1%.

The purpose of this study was to assess the cosmetic appearance of commonly marketed facial cosmetics when used after the application of metronidazole gel 1%. An observational. open-label, single-site study was conducted with women (N=30) aged 20 to 75 years and diagnosed with moderate papulopustular rosacea (investigator global severity score of 3). After cleansing the face with a gentle skin cleanser, participants applied metronidazole gel 1% once daily before applying their usual facial foundation. Two surveys were conducted: (1) investigator assessment of cosmetic appearance; and (2) participant assessment of cosmetic appearance. The investigator also evaluated erythema, disease severity, and tolerability at baseline and week 2. Adverse events were collected. The 28 per-protocol (PP) participants had a mean age (standard deviation [SD]) of 54.0 (10.3) years and a mean duration (SD) of rosacea of 15.4 (13.2) years. The median response score for both the investigator and participant assessments of cosmetic appearance was 10 (best) for each survey question. Signs and symptoms of rosacea did not increase with use of metronidazole gel 1% and the participants' selected cosmetic regimen. At baseline all 28 participants were classified as having moderate erythema. At week 2, 18 (64%) participants were classified as having moderate erythema and 10 (36%) mild. At baseline all 28 (100%) participants were classified as having moderate rosacea according to the investigator global severity score. At week 2, 10 (36%) participants were classified as mild and 18 (64%) moderate. In addition, few participants reported cutaneous irritation during the study. At week 2, 10 participants had dryness, 2 had itching, 8 had scaling, and 2 had stinging/burning. According to surveys completed by the investigator and the participants themselves, most participants had a good cosmetic appearance with their facial foundation cosmetics that were applied after metronidazole gel 1%. The use of various cosmetic regimens after application of metronidazole gel 1% did not cause rosacea symptoms to worsen and treatment was well-tolerated.

Sequential treatment with triple combination cream and intense pulsed light is more efficacious than sequential treatment with an inactive (control) cream and intense pulsed light in patients with moderate to severe melasma.

BACKGROUND: Triple combination (TC) cream is a stable combination of fluocinolone acetonide 0.01%, hydroquinone 4%, and tretinoin 0.05% and is currently the only hydroquinone-containing drug approved by the Food and Drug Administration for the treatment of melasma. OBJECTIVE: To evaluate the safety and efficacy of TC cream when used sequentially with intense pulsed light (IPL) treatments in patients with moderate to severe melasma. MATERIALS & METHODS: This was a 10-week, split-face study in which 56 patients with symmetrical melasma lesions were treated with TC cream on one side of the face and an inactive control cream on the other side of the face. Patients also had two IPL treatments at weeks 2 and 6. (Topical treatment was suspended during IPL treatments ± 1 day.) RESULTS: Melasma severity was significantly less with TC cream and IPL than with inactive cream and IPL at weeks 6 (p=.007) and 10 (p=.002). Improvement in melasma was greater with TC cream and IPL than with inactive cream and IPL according to investigator and patient evaluations at weeks 6 and 10 (p<.001 for both time points). Treatment with TC cream and IPL was well tolerated. CONCLUSION: The results of this study suggest that TC cream and IPL treatment is an effective and safe treatment option for patients with melasma.