Fixed-combination halobetasol propionate and tazarotene topical lotion decreases TNF-α and IL-17A levels in psoriatic lesions.

OBJECTIVE: Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) is approved for the treatment of plaque psoriasis in adults, with a demonstrated efficacy and safety profile in phase 3 trials. This study examined the effect of HP/TAZ on the reduction of tumor necrosis factor alpha (TNF-α) and interleukin 17 A (IL-17A) and its correlation to psoriasis improvement. MATERIALS AND METHODS: Ten adults with mild-to-moderate plaque psoriasis and 2 symmetrical plaques self-applied HP/TAZ (treated plaque) or vehicle lotion (untreated plaque) for 12 weeks. At baseline and each study visit (weeks 2, 4, 8, and 12), Investigator's Global Assessment (IGA) score and erythema, scaling, and induration were assessed. Additionally, D-squame tape strips were utilized to quantify TNF-α and IL-17A in target lesions by enzyme-linked immunosorbent assay. RESULTS: Significant improvements in mean IGA score in HP/TAZ-treated compared with untreated plaques were evident at week 2 and maintained through week 12 (p < 0.003). HP/TAZ significantly reduced TNF-α levels at weeks 4 through 12 (p < 0.03) and IL-17A levels at weeks 2 through 8 (p < 0.05) in treated compared with untreated plaques. CONCLUSIONS: HP/TAZ was highly effective in treating psoriasis plaques and, although HP/TAZ is not a biologic, effectively reduced cytokine-associated inflammatory markers that drive psoriatic disease.

Plant-Derived Extracts Plus Vitamin E and/or Aloe Vera Protect Against Intrinsic/Extrinsic Stressor in Human Skin: In Vitro and Clinical Evidence.

BACKGROUND: Humans are exposed to physical, biological, chemical, and psychological stressor throughout their life span. In recent years many medicinal plants have been shown to induce stress adapting and protective functions. Plant-derived extracts and vitamin E exhibit stress protection or resistance by normalizing cellular homeostasis and enhancing resistance to toxic stimuli to overcome cellular damage. Here we report the evaluation of a topical preparation (product test materials; PTM) containing an ingredient blend of Rhodiola Rosea, Eleutherococcus Senticosus (Siberian Ginseng), Rhaponticum Carthamoides, Inonotus Obliqus, and Slegainella Lepidophylla as the base formula and tested the addition of Lespedeza Capitata (leaf/stem) extract plus vitamin E and/or Aloe Vera to determine the induced protective functions in human skin when challenged with intrinsic and extrinsic stressors. METHODS: The base topical preparation plus Lespedeza Capitata extract plus vitamin E or the base topical preparation plus vitamin E and Aloe Vera were assayed in vitro on (a) intrinsically stressed excised abdominoplasty skin, (b) full thickness (FT) skin equivalent models post-treated with a combination of ultra-violet (UV) B light (250 mJ/cm2) and diesel particular matter (DPM) (75 µg/mL) skin, for their effect on antioxidant, inflammation, and stress biomarker geners. Additionally, the bioadaptive activity of the PTMs was confirmed in providing resilience and protection against UV-induced erythema. For example, in a clinical study, daily topical application of the PTMs on the buttocks of 20 woman (18-78 years old), average age of 51.1 years, median body mass index (BMI) of 26.5 for 8 weeks followed by 2 minimal erythema dose (MED) of UVB exposure was accessed 24 hours after irradiation. Statistical analysis was performed by t-test and ANOVA, repectively. RESULTS: Pretreatment with the topical PTMs on intrsinically stressed skin significantly reduced the expression of the stress gene biomarkers, p53, pro-inflammatory cytokines Interleukin-1ß (IL-1ß) and Tumor Necrosis Factor-α (TNFα) and the pro-apoptotic BCL2 associated X, apoptosis regulator (BAX) values compared to controls. Topical application of the PTMs on Full Thickness (FT) human skin treated with UVB light and DPM significantly enhanced the stress response by activating heat shock transcription factor 4 (HSF4) and heat shock protein family B (small) member 1 (HSPB1) gene levels belonging to the heat shock protein (HSP) family by significantly increasing the expression of heme oxygenase 1 (HMOX1). At the same time, significantly reducing IL-1ß levels were observed plus protection of skin cells from toxicity ocurred by significantly increasing the expression of B-cell lymphoma 2 (BCL2) (anti-apoptotic gene). In the clinical study, daily topical applications of the PTMs for 8 weeks followed by 2MED of UVB irradiation with clinical assessment 24 hours later revealed a significantly reduced intensity of erythema when compared to the buttock region treated with UVB alone. CONCLUSIONS: The PTMs containing adaptogen ingredients may confer stress resistance and induce stress protective responses against intrinsic as well as extrinsic stressors as demonstrated by the obtained in vitro and clinical evidence.

Vehicle Effects on the Rosacea Skin Barrier.

BACKGROUND: Inflammatory papulopustular rosacea produces sensitive facial skin. Thus, medications designed for rosacea require careful vehicle development to insure optimal drug delivery in an environment suitable for barrier repair. OBJECTIVE: The objective of this phase 1 study was to elucidate the barrier effects of an investigational topical minocycline anhydrous gel 3% in subjects with inflammatory rosacea. METHODS: 31 male or female subjects with all complexion types and moderate facial rosacea, defined as 15+ inflammatory facial lesions, were enrolled in this single-site study to evaluate the effects of an investigational topical 3% minocycline anhydrous gel vehicle on skin barrier function; the new topical minocycline gel is an investigational product under development and has completed a phase 2b study in rosacea patients. Following a 30-minute acclimation period, subjects underwent a one-minute transepidermal water loss (TEWL) measurement on the left cheek and triplicate pin probe corneometry measurements from the right cheek. Subjects used the investigational topical 3% minocycline anhydrous gel every evening and returned to the research center at day 1, week 2, and week 4. RESULTS: 30/31 subjects completed the research study. The study medication produced a 23% (P=0.003) increase in skin hydration at day 1 and maintained the hydration increase with a 22% (P=0.003) increase at week 2 and a 20% increase (P=0.001) at week 4. Simultaneously, skin barrier function also improved with an 11% reduction in TEWL at day 1 followed by an 18% reduction in TEWL at week 2 (P=0.001) and a 28% decrease in TEWL at week 4 (P<0.001). This improvement in skin barrier was due to a combination of skin healing and the moisturizing properties of the investigational topical 3% minocycline anhydrous gel medication evaluated in this study. CONCLUSION: The investigational topical 3% minocycline anhydrous gel decreases TEWL, indicating barrier repair, while increasing corneometry measurements, indicating improved skin hydration. J Drugs Dermatol. 2021;20(6):630-632. doi:10.36849/JDD.6105Visit the rosacea resource center.

The First of Two One-Year, Multicenter, Open-Label, Repeat-Dose, Phase II Safety Studies of PrabotulinumtoxinA for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients.

BACKGROUND: PrabotulinumtoxinA is a 900-kDa botulinum toxin type A produced by Clostridium botulinum. OBJECTIVES: The authors sought to investigate the safety of prabotulinumtoxinA for treatment of glabellar lines. METHODS: This was a multicenter, open-label, repeat-dose, 1-year phase II safety study. Adults with moderate to severe glabellar lines at maximum frown, as assessed by the investigator on the validated 4-point photonumeric Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), were enrolled. On day 0, patients received an initial treatment of 20 U prabotulinumtoxinA (4 U/0.1 mL freeze-dried formulation injected into 5 target glabellar sites). On and after day 90, patients received a repeat treatment (RT) if their Glabellar Line Scale score was ≥2 at maximum frown by investigator assessment. Safety was evaluated throughout the study. RESULTS: The 352 study patients received a median total dose of 60 U, that is, 3 treatments per year. Fifty-one patients (14.5%) experienced adverse events (AEs) assessed as possibly study drug related; 11.1% experienced study drug-related AEs after the initial treatment. With each RT, progressively lower percentages of patients experienced study drug-related AEs. Six patients (1.7%) experienced study drug-related AEs of special interest: 3 eyelid ptosis (0.9%), 2 speech disorder (0.6%), and 1 blepharospasm (0.3%). Seven patients (2.0%) experienced serious AEs; none were study drug related. Of the 2393 samples tested, 2 patients (0.6%) tested positive for antibotulinum toxin antibodies at a single postbaseline visit. CONCLUSIONS: The safety of RTs of 20 U of prabotulinumtoxinA for moderate to severe glabellar lines was first established in this early phase II study based on a broad range of outcomes.

The Second of Two One-Year, Multicenter, Open-Label, Repeat-Dose, Phase II Safety Studies of PrabotulinumtoxinA for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients.

BACKGROUND: PrabotulinumtoxinA is a 900-kDa botulinum toxin type A produced by Clostridium botulinum. OBJECTIVES: The authors sought to investigate the safety of prabotulinumtoxinA for treatment of glabellar lines. METHODS: This was a multicenter, open-label, repeat-dose, 1-year phase II safety study. Adults with moderate to severe glabellar lines at maximum frown, as independently assessed by both investigator and patient on the validated 4-point photonumeric Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), were enrolled. On day 0, patients received an initial treatment (IT) of 20 U prabotulinumtoxinA (4 U/0.1 mL final vacuum-dried formulation injected into 5 glabellar sites). On and after day 90, patients received a repeat treatment (RT) if their Glabellar Line Scale score was ≥2 at maximum frown by investigator assessment. Safety outcomes were evaluated throughout the study. RESULTS: The 570 study patients received a median total dose of 60 U, that is, 3 treatments. Sixty-one patients (10.7%) experienced adverse events (AEs) assessed as possibly study drug related; 6.5% experienced study drug-related AEs after the IT. With each RT, progressively lower percentages of patients experienced study drug-related AEs. Eight patients (1.4%) experienced study drug-related AEs of special interest: 5 experienced eyelid ptosis (0.9%), 3 eyebrow ptosis (0.5%), 1 blepharospasm (0.2%), and 1 blurred vision (0.2%). Seven patients (1.2%) experienced serious AEs, but none were study drug related. A total of 4060 serum samples were tested for antibotulinum toxin antibodies; no seroconversion was observed. CONCLUSIONS: The safety of RTs of 20 U of prabotulinumtoxinA for moderate to severe glabellar lines was confirmed in this second phase II study based on a broad range of outcomes.

Oral Sarecycline for Treatment of Papulopustular Rosacea: Results of a Pilot Study of Effectiveness and Safety.

BACKGROUND: Cutaneous rosacea is a common inflammatory skin disorder that often presents with facial papulopustular lesions that are frequently bothersome to patients. Studies have shown oral sarecycline to be effective and safe for acne, with a low risk of side effects that are historically associated with other tetracycline-class drugs such as doxycycline and minocycline, in addition to offering a reduced risk of emergence of resistant bacteria due to its narrow-spectrum of antibiotic activity. Oral sarecycline is FDA-approved for the treatment of acne (2018). OBJECTIVE: A pilot study to evaluate the efficacy and safety of oral sarecycline in papulopustular rosacea. METHODS: A 12-week, prospective, parallel-group, investigator-blinded, controlled pilot study was completed evaluating once-daily sarecycline, using weight-based oral dosing as recommended for acne vs control (multivitamin tablet), for the treatment of moderate-to-severe papulopustular rosacea in adult subjects (n=102), aged ≥18 years. The primary efficacy endpoint was Investigator's Global score (IGA; clear or almost clear) and percent reduction in inflammatory lesion count at week 12. Safety and tolerability assessments were performed as well. RESULTS: A total of 102 subjects were randomized; 97 completed the study. At week 12, IGA improvement was significantly greater for oral sarecycline when compared to the control (P<0.0001). Furthermore, absolute and percent reductions in inflammatory lesion counts were significantly greater in the sarecycline group for all weeks (4, 8, and 12) when compared to the control (P<0.001). Significant improvement in facial burning, erythema, and pruritus was reported in the sarecycline group, when compared to the control (P<0.05). No serious AEs were reported. CONCLUSION: Sarecycline was effective, safe, and well-tolerated for treating papulopustular rosacea in adults with marked superiority in efficacy compared to subjects in the control group. With its narrow-spectrum activity, oral sarecycline may be a good option for the treatment of papulopustular rosacea. Additional studies are warranted to confirm the positive results of this pilot study.

Clinical Evaluation of a Nature-Based Bakuchiol Anti-Aging Moisturizer for Sensitive Skin.

BACKGROUND: Patients with sensitive skin find topical retinoid use for anti-aging purposes challenging due to irritation. Bakuchiol, a meroterpene from the Psoralea corylifolia seed, has retinol functionality through retinol-like regulation of gene expression. OBJECTIVE: This research examined the tolerability, efficacy, and barrier effects of a nature-based bakuchiol-containing cleanser and moisturizer in subjects with sensitive skin. METHODS: 60 female subjects Fitzpatrick skin types I–V age 40–65 years with sensitive mild to moderate photodamaged skin were enrolled in this 4 week study. A sensitive skin panel was constructed: 1/3 eczema/atopic dermatitis, 1/3 rosacea, 1/3 cosmetic intolerance syndrome. Subjects used a nature-based cleanser and moisturizer twice daily and underwent transepidermal water loss (TEWL), corneometry, tolerability assessments, and efficacy assessments at baseline, 5–10 minutes post-application, and week 4. RESULTS: The skin care products were well tolerated and efficacious (P<0.001) in terms of investigator assessed improvement in visual smoothness, tactile smoothness, clarity, radiance, overall appearance, and global anti-aging. Cheek corneometry measurements demonstrated a statistically significant 16% increase in skin moisture content (P<0.001). CONCLUSION: A bakuchiol nature-based anti-aging moisturizer is well tolerated and effective in individuals with sensitive skin.J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5522.

Clinical Benefits of Circadian-based Antioxidant Protection and Repair.

Skin activities follow endogenous circadian rhythms resulting in differences between daytime and nighttime properties. To address the variations in skin needs, a novel circadian-based dual serum system (LVS) was developed. A 12-week, double-blind, randomized, regimen-controlled, multi-center study was conducted to assess the efficacy and tolerability of LVS on subjects presenting with moderate-severe photodamage. 61 Female subjects (36–65 years; Fitzpatrick skin types I–VI) completed the study. The active group received LVS (daytime serum and nighttime serum) and basic skin care regimen (moisturizer and SPF 35 sunscreen), while the control group received the basic skin care regimen only. In addition to clinical grading, subject self-assessment questionnaires, and standardized photography, punch biopsies were taken in a subset of subjects for immunohistochemistry. Additionally, swab samples were taken for skin surface oxidation analysis. Significant improvements over control were observed in the active group in Radiance (weeks 4, 8, and 12), Overall Photodamage, Tactile Toughness, and Global Fine Lines/Wrinkles (week 12). Biopsy results, skin swab analysis and standardized photographs support the clinical grading findings. At all follow-up visits, LVS was consistently highly rated over control by subjects, with a significant proportion of subjects agreeing at week 12 that LVS “improved the radiance of my skin,” and “improved the overall health and look of my skin”. Results from this study suggest that LVS may provide essential protective and reparative effects to skin exposed to the damaging effects of environmental factors, and also demonstrates the value of including skin circadian rhythm-based concepts in a topical skincare regimen. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5355.

Demonstration of the Antioxidant Capabilities of a Product Formulated With Antioxidants Stabilized in Their Reduced Form

Oxidative damage from reactive oxygen species is instrumental in aging. Topical antioxidants are used in many cosmeceuticals to provide appearance benefits; however, the activity of these antioxidants may be questionable. This research validated the activity of L-ascorbic acid and L-glutathione in the studied facial product and correlated this activity with clinical appearance improvement following 12 weeks of use. J Drugs Dermatol. 2020;19(1):46-49. doi:10.36849/JDD.2020.3947

Pilot study: Autologous platelet-rich plasma used in a topical cream for facial rejuvenation.

BACKGROUND: Platelet rich plasma (PRP) is traditionally used as an injectable material for enhanced healing, hair growth, and facial rejuvenation. AIMS: This research examined the novel use of topical autologously sourced PRP added to a preservative cosmetic base and applied twice daily to the face following electroporation for 8 weeks. METHODS: 20 healthy female and male subjects 30-60 years of age were enrolled in this single-site, investigator blinded, vehicle controlled split-face study to evaluate the effect of a PRP-containing serum versus the serum alone on facial photoaging. RESULTS: 90 day stability for the PRP in a preservative serum was achieved with refrigeration at 4 degrees Celsius. Facial skin biopsy histologic findings included improved rete peg architecture. Immunohistochemical analysis showed upregulation for collagen type I with qPCR data demonstrating concomitant upregulation of mRNA for collagen after 8 weeks of topical PRP use. CONCLUSION: These pilot study findings may indicate value for topical PRP in facial rejuvenation.

Natural Skin Care Products as Adjunctive to Prescription Therapy in Moderate to Severe Rosacea

Background: 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<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<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: NCT03392558 J Drugs Dermatol. 2019;18(2):141-146.

Cosmeceuticals: What's Real, What's Not.

Cosmeceuticals are cosmetics that promise to deliver physiologically relevant benefits without the incorporation of prescription drugs. To entice consumers to purchase these premium priced products, a story must be told of how the cosmeceutical delivers on these appearance improvement promises. The backbone of any cosmeceutical skin care regimen is facial cleansing and moisturizing. This article reviews the novel ingredients and technologies used to achieve these benefits examining what is real and what is not.

A Double-Blind Randomized Pilot Study Evaluating the Safety and Efficacy of Topical MEP in the Facial Appearance Improvement of Estrogen Deficient Females

Facial skin aging is accelerated in postmenopausal females due to decreased collagen, reduced hydration, and loss of skin elasticity constituting the characteristics of estrogen deficient skin (EDS). The presence of estrogen receptors on dermal fibroblasts and epidermal keratinocytes confirms the role of estrogen in skin health. This research examined the efficacy and tolerability of topical methyl estradiolpropanoate (MEP) as an anti-aging cosmeceutical with estrogen like cutaneous effects in postmenopausal women who had never taken hormone replacement therapy (HRT). MEP was applied to the face twice daily for 14 weeks but was metabolized in the skin to an inactive compound avoiding estrogen side effects, as demonstrated by the safety study. The efficacy study investigator noted MEP induced statistically significant improvement from baseline at week 14 in dryness (P<0.001), laxity (P=0.001), atrophy (P=0.003), and dullness (P<0.001) as compared to vehicle. Four of nine subjects in the biopsy sub study demonstrated an increase in fibroblasts estrogen receptor staining. The novel concept of a safe and efficacious soft estrogen facial cosmeceutical may provide appearance benefits for postmenopausal women.

Topical Oxymetazoline Cream 1.0% for Persistent Facial Erythema Associated With Rosacea: Pooled Analysis of the Two Phase 3, 29-Day, Randomized, Controlled REVEAL Trials

Background: 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 ≥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<0.001). Individual CEA and SSA scores and reduction in facial erythema (digital image analysis) favored oxymetazoline over vehicle (P<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.

Efficacy and safety of oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea: Findings from the 52-week open label REVEAL trial.

BACKGROUND: Limited treatments are available for persistent erythema of rosacea. OBJECTIVE: To examine the long-term safety and efficacy of oxymetazoline cream 1.0% in patients with rosacea with moderate-to-severe persistent erythema. METHODS: Patients applied oxymetazoline once daily for 52 weeks. Safety assessments included treatment-emergent adverse events (TEAEs), skin blanching, inflammatory lesion counts, telangiectasia, disease severity, and rebound effect. Efficacy was assessed by the Clinician Erythema Assessment and Subject Self-Assessment composite score at 3 and 6 hours after the dose on day 1 and at weeks 4, 26, and 52. RESULTS: Among 440 patients, 8.2% reported treatment-related TEAEs; the most common were application-site dermatitis, paresthesia, pain, and pruritus. The rate of discontinuation due to adverse events (mostly application-site TEAEs) was 3.2%. No clinically meaningful changes were observed in skin blanching, inflammatory lesions, or telangiectasia. At week 52, 36.7%, and 43.4% of patients achieved a 2-grade or greater composite improvement from baseline in both Clinician Erythema Assessment and Subject Self-Assessment 3 and 6 hours after a dose, respectively. Less than 1% of patients experienced a rebound effect following treatment cessation. LIMITATIONS: A vehicle-control group was not included. CONCLUSION: This long-term study demonstrated sustained safety, tolerability, and efficacy of oxymetazoline for moderate-to-severe persistent erythema of rosacea.

Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the First REVEAL Trial.

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.