Rosacea is a disease resulting from dysregulation of innate, adaptive, and neurovascular immune systems. Inflammatory pathways activated in rosacea can explain many of its signs and symptoms. Current treatments address some of these inflammatory processes, alleviating erythema and decreasing papules and pustules. However, for the majority of patients, complete clearance of these features is not currently achievable even with combination therapy. There is a need to address the spectrum of inflammatory processes involved in rosacea and for more efficacious agents with the goal of providing complete clearance for patients.J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.5187
Papulopustular rosacea (PPR) is a chronic inflammatory disorder characterized by facial papules, pustules, and persistent erythema. It is highly prevalent and associated with adverse impact on quality of life and depression. The etiology of rosacea is multifactorial. In addition to neurovascular dysregulation, the facial skin of patients with rosacea is affected by augmented proinflammatory immune responses. The principal active cathelicidin peptide (LL-37) is highly concentrated in skin affected by rosacea and can contribute to acute inflammation. Moreover, PPR is characterized by the presence of inflammatory infiltrates that accompany flares, along with a heightened immune response involving neutrophilic infiltration and increased gene expression of IL-8.5 In addition to exogenous factors (including UV light, heat, and alcohol), it may be triggered by Demodex folliculorum mites. Some studies of PPR observed higher mite densities compared to controls. Therefore, a multitude of factors can activate neurovascular and/or immune responses, and consequential inflammation leading to flares of rosacea.
Azelaic acid (AzA) 15% gel has been available in the United States for slightly over a decade, approved for treatment of the inflammatory lesions (papules and pustules) of rosacea. Efficacy and safety have been established in multiple studies both as monotherapy and in combination with oral doxycycline. Azelaic acid 15% gel has been shown not to induce epidermal permeability barrier impairment, and proper skin care reduces the likelihood of neurosensory adverse effects of stinging and burning that can affect a subset of patients with rosacea. Azelaic acid 15% gel appears to produce a quicker onset of clinical effect than metronidazole in some patients when either agent is used in combination with subantimicrobial dose doxycycline; however, both topical agents are effective when used in this combination approach for papulopustular rosacea (PPR). Although more information is needed on the modes of action of AzA in the treatment of rosacea, downregulation of the cathelicidin pathway appears to be one operative mode of action based on in vitro and in vivo studies, including data from patients treated with AzA 15% gel for PPR. Azelaic acid 15% foam is currently in the latter stages of development for PPR, with pivotal studies demonstrating efficacy and favorable tolerability, including a very low incidence of stinging, burning, and itching even without the use of designated skin care products.J Drugs Dermatol. 2014;13(suppl 12):s101-s107.
Rosacea is a common chronic inflammatory dermatosis with a variety of clinical manifestations. Rosacea primarily affects the central face, and includes papules, pustules, erythema, telangiectasias, perilesional redness, phymatous changes, and even ocular involvement. Symptoms may vary among different patients and even vary over time in an individual patient. Central facial redness affects many adults and can be an indicator of the chronic inflammatory disease rosacea. Rosacea is a clinical diagnosis based on the patient’s history, physical examination, and exclusion of other disorders. It is under-diagnosed, particularly in individuals with skin of color. The goal of this article is to provide clinicians with the tools and understanding needed to correctly identify rosacea and differentiate it from other conditions that have overlapping signs and symptoms.J Drugs Dermatol. 2019;18(9):888-894.
The purpose of this pilot study was to assess the safety and effectiveness of MFU-V for improving the signs and symptoms of erythematotelangiectatic rosacea. Healthy adults with a clinical diagnosis of erythematotelangiectatic rosacea were enrolled (N=91). Eligible subjects had baseline Clinician Erythema Assessment (CEA) scores ≥3 and Patient Self-Assessment (PSA) of erythema scores ≥2. Subjects were randomized to receive one or two low-density MFU-V treatments or one or two high-density MFU-V treatments. Subjects were evaluated at 90, 180, and 365 days after treatment. The primary effectiveness endpoint was treatment success, defined as a 1-point change in CEA scores at 90 days post-treatment.J Drugs Dermatol. 2019;18(6):522-531.
This study used matching-adjusted indirect comparison (MAIC) to compare patient-reported outcomes from survey data evaluating rosacea treatments. Outcomes of interest included percentages of patients reporting concerns and side effects and measures of importance of the concerns and tolerability of the side effects. Patients in each analysis (MG vs AAF and MC vs AAF) were matched using stabilized inverse propensity scores.J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.3679
Rosacea is characterized by irritation associated with erythema, telangiectasias and papules/pustules. Whole formula nature-based sensitive skin products are formulated to maintain skin barrier and appropriate hydration that can lead to soothing benefits. Objective: To evaluate the efficacy and tolerability of a regimen consisting of a cleanser containing natural oils, beeswax, and witch hazel and day and night creams containing natural oils, glycerin, and botanical anti-inflammatories (NR); and a synthetic dermatologist-recommended regimen of cetyl alcohol, sodium lauryl sulphate-containing cleanser, and glycerin, polyisobutene-containing lotion (CR) in subjects with rosacea. Methods: 80 female subjects with rosacea who received 6 weeks of 0.75% metronidazole gel, were randomized to receive NR or CR, twice daily, for 4 weeks in conjunction with the gel. Blinded investigator global assessment of rosacea, investigator-rated, and subject-rated overall skin appearance was assessed using a 5-point scale (0=none, 4=severe) at baseline, 2 weeks, and 4 weeks. Noninvasive skin assessments for skin hydration and skin barrier function were made by corneometry and TEWL, respectively. Results: NR resulted in improvement in investigator global assessment of rosacea measures at 4 weeks from baseline (erythema, 28%; telangiectasia, 26%; papules/pustules, 34%: P less than 0.001) and CR resulted in a 8 to 12% improvement. Differences between treatments were statistically significant. Overall skin appearance measured by the investigator was clinically and statistically improved from baseline by 32% and 12% with NR and CR, respectively. Overall skin appearance measured by subjects was improved by both NR and CR from baseline with no differences between treatments. Both regimens improved barrier function from baseline to week 4 (13%, NR; 14%, CR). NR decreased hydration by 21% from baseline at week 4 while CR increased hydration by 14% (P less than 0.001 from NR). No clinically significant tolerability issues were reported in either regimen at week 4. Conclusion: NR was effective, well tolerated, and superior to CR in the management of rosacea, concomitantly treated with metronidazole. National Clinical Trial Identifier: NCT03392558J Drugs Dermatol. 2019;18(2):141-146.
Facial redness is a common difficult to control cosmetic problem representing various phases of rosacea. Using anti-inflammatory/antioxidant botanicals in moisturizer formulations is a possible approach to minimizing the erythema. This research utilized a common facial cleanser, but only applied the botanically based moisturizer to one half face to properly assess efficacy. 30 female subjects Fitzpatrick skin types I-IV 30-55 years of age with mild to moderate chronic facial redness, defined as a redness score of 3-6 on a 10-point scale, were enrolled. By the end of week 4, statistically significant improvement was seen on the cleanser/mask treated side in scaling (P less than 0.001), flaking (P less than 0.001), tactile smoothness (P less than 0.001), textural smoothness (P less than 0.001), firmness (P less than 0.001), radiance (P less than 0.001), luminosity (P less than 0.001), and overall appearance (P less than 0.001). Thus, cosmetic moisturizers may be useful in reducing facial redness.J Drugs Dermatol. 2018;17(6):671-676.
Rosacea is common inflammatory facial dermatosis. Rosacea has variable manifestations including facial flushing, central facial erythema, telangiectasias, and papulopustular lesions. Treatment of rosacea is challenging given the varied manifestations and incompletely understood etiology, but the treatment of papulopustular presentations often relies on oral antibiotics. Tetracyclines, specifically doxycycline, are the most commonly prescribed antibiotics for rosacea. Other antibiotics that can be used include macrolides, commonly azithromycin, and rarely, metronidazole. This paper will review the evidence for the use of antibiotics in the treatment of rosacea.
J Drugs Dermatol. 2019;18(6):506-513.
Rosacea is a chronic dermatologic condition with limited treatment options. METHODS: Data were pooled from two identically designed phase 3 trials. Patients with moderate to severe persistent erythema of rosacea were randomized to receive oxymetazoline cream 1.0% or vehicle once daily for 29 days and were followed for 28 days posttreatment. The primary efficacy outcome was the proportion of patients with greater than equal to 2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) at 3, 6, 9, and 12 hours postdose, day 29. RESULTS: The pooled population included 885 patients (78.8% female); 85.8% and 91.2% had moderate erythema based on CEA and SSA, respectively. The primary outcome was achieved by significantly more patients in the oxymetazoline than vehicle group (P less than 0.001). Individual CEA and SSA scores and reduction in facial erythema (digital image analysis) favored oxymetazoline over vehicle (P less than 0.001). The incidence of treatment-emergent adverse events was low (oxymetazoline, 16.4%; vehicle, 11.8%). No clinically relevant erythema worsening (based on CEA and SSA) was observed during the 28-day posttreatment follow-up period (oxymetazoline, 1.7%; vehicle, 0.6%). CONCLUSION: Oxymetazoline effectively reduced moderate to severe persistent facial erythema of rosacea and was well tolerated.J Drugs Dermatol. 2018;17(11):1201-1208.
This was a single-center, prospective study of 17 subjects with facial telangiectasias and skin types I–III. Three monthly treatments were performed using this specific filter, with follow-up visits at 1, 3, and 6 months. Telangiectasia improvement was assessed by the investigator and subjects using a 5-point scale. Facial photographs and safety assessments were obtained at each visit. Subject discomfort was evaluated using a visual analog scale (VAS) immediately posttreatment, and subject downtime was recorded at each subsequent visit.
J Drugs Dermatol. 2020;19(9):844-850. doi:10.36849/JDD.2020.4834
Persistent facial erythema is a clinically challenging feature of rosacea. OBJECTIVE: To evaluate persistent erythema reduction on the first day of treatment from pooled data from two pivotal trials of topical oxymetazoline cream 1.0% (oxymetazoline) in persistent facial erythema of rosacea. METHODS: In two identically designed, phase 3, multicenter trials, adults with moderate to severe persistent facial erythema of rosacea (Clinician Erythema Assessment [CEA] grade ≥3 and Subject Self-Assessment [SSA] grade ≥3) were randomized 1:1 to once-daily topical oxymetazoline or vehicle; the primary efficacy endpoint was ≥2-grade composite CEA and SSA improvement from baseline on day 29. This post hoc analysis evaluated the proportion of patients achieving ≥1-grade composite and individual CEA and SSA improvement at 1, 3, 6, 9, and 12 hours postdose on day 1 (N=885). RESULTS: Significantly more patients achieved ≥1-grade composite and individual CEA and SSA improvement with the first application of oxymetazoline than with vehicle (P less than 0.001) at all postdose time points, beginning with hour 1. Day 1 safety assessments were similar between treatments. LIMITATIONS: Short-term, post hoc analysis.
Rosacea is a chronic dermatologic condition with limited treatment options. Objective: This phase 2 study evaluated the optimal oxymetazoline dosing regimen in patients with moderate to severe persistent facial erythema of rosacea. Methods: Patients were randomly assigned to oxymetazoline cream, 0.5%, 1.0%, or 1.5%, or vehicle, administered once daily (QD) or twice daily (BID) for 28 consecutive days. The primary efficacy endpoint was the proportion of patients with ≥2-grade improvement from baseline on the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment of erythema (SSA-1) on day 28. Safety assessments included treatment-emergent adverse events and dermal tolerability. Results: A total of 356 patients were treated (mean age, 50.0 years; 80.1% female). The proportions of patients achieving the primary endpoint were significantly higher with oxymetazoline 0.5% QD (P=0.049), 1.0% QD (P=0.006), 1.5% QD (P=0.012), 1.0% BID (P=0.021), and 1.5% BID (P=0.006) versus their respective vehicles. For both QD and BID dosing, the efficacy of oxymetazoline 1.0% was greater than the 0.5% dose and comparable to the 1.5% dose. Safety and application-site tolerability were similar across groups. Limitations: Short-term treatment period. Conclusion: Oxymetazoline 1.0% QD provided the optimal dosing regimen and was selected for evaluation in phase 3 rReclinical studies.J Drugs Dermatol. 2018;17(3):308-316.
An unmet need exists for a safe, tolerable, effective treatment for moderate to severe persistent facial erythema in patients with rosacea. This pivotal phase 3, multicenter, double-blind study evaluated the efficacy and safety of topical oxymetazoline in patients with facial erythema associated with moderate to severe rosacea. Patients were randomly assigned to treatment with oxymetazoline hydrochloride cream 1.0% or vehicle applied once daily for 29 days, and were followed for 28 days posttreatment. The primary efficacy outcome was having at least a 2-grade decrease from baseline on both the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment for rosacea facial redness (SSA) scales (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Safety assessments included treatment-emergent adverse events (TEAEs) and posttreatment worsening of erythema (composite CEA/SSA increase of 1-grade severity from baseline; rebound effect). A total of 440 patients (mean age, 49.5 years; 78.9% females) were randomized (oxymetazoline, n=222; vehicle, n=218); most had moderate erythema. On day 29, significantly greater proportions of oxymetazoline recipients achieved the primary efficacy outcome at each time point (P less than 0.02) and overall (P less than 0.001) compared with vehicle recipients. The incidence of discontinuation due to TEAEs was low in both groups (oxymetazoline group, 1.8%; vehicle group, 0.5%). The most common TEAEs reported during the entire study period were application-site dermatitis, application-site erythema, and headache in the oxymetazoline group (1.4% each), and headache (0.9%) in the vehicle group. Following cessation of treatment, low proportions of patients experienced rebound effect (oxymetazoline group, 2.2%; vehicle group, 1.1%). Oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in patients with moderate to severe persistent facial erythema of rosacea.J Drugs Dermatol. 2018;17(1):97-105.
There is currently a lack of data on the simultaneous treatment of different features of rosacea. Individually, ivermectin 1% (IVM) cream and brimonidine 0.33% (BR) gel have demonstrated efficacy on inflammatory lesions and persistent erythema, respectively. OBJECTIVE: To evaluate the efficacy, safety, patient satisfaction, and optimal timing of administration of IVM associated with BR (IVM+BR) versus their vehicles in rosacea (investigator global assessment [IGA] ≥3). METHODS: Multicenter, randomized, double-blind study including subjects with rosacea characterized by moderate to severe persistent erythema and inflammatory lesions. The active treatment group included the IVM+BR/12 weeks subgroup (once-daily BR and once-daily IVM for 12 weeks), and the IVM+BR/8 weeks subgroup (once-daily BR vehicle for 4 weeks followed by once-daily BR for the remaining 8 weeks and once-daily IVM for 12 weeks). The vehicle group received once-daily BR vehicle and once-daily IVM vehicle for 12 weeks. RESULTS: The association showed superior efficacy (IGA success [clear/almost clear]) for erythema and inflammatory lesions in the total active group (combined active subgroups) compared to vehicle (55.8% vs. 36.8%, P=0.007) at week 12. The success rate increased from 32.7% to 61.2% at hour 0 and hour 3, respectively, in the IVM+BR/12 weeks subgroup, and from 28.3% to 50% in the IVM+BR/8 weeks subgroup. Reductions in erythema and inflammatory lesion counts confirmed the additive effect of BR to IVM treatment. Subjects reported greater improvement in the active subgroups than in the vehicle group, and similar rates for facial appearance satisfaction after the first 4 weeks of treatment in both active subgroups. All groups showed similar tolerability profiles. CONCLUSION: Concomitant administration of IVM cream with BR gel demonstrated good efficacy and safety, endorsing the comprehensive approach to this complex disease. Early introduction of BR, along with a complete daily skin care regimen may accelerate treatment success without impairing tolerability.J Drugs Dermatol. 2017;16(9):909-916.
Objective of this open dermocosmetic study was to investigate the efficacy and tolerability of a skin care product containing the anti-inflammatory licochalcone A and the TRPV1 antagonist trans-t-butylcyclohexanol in subjects with sensitive skin prone to redness and rosacea.J Drugs Dermatol. 2017;16(6):605-611.