Validity and reliability of the Rosacea Area and Severity Index: A novel scoring system for clinical assessment of rosacea severity.

BACKGROUND: Rosacea is a common chronic inflammatory facial skin disorder. Standardized evaluation of the severity and extent of rosacea is important for baseline assessment and treatment effect. The currently used Investigator's Global Assessment (IGA) is unspecific and fails to consider subtypes/phenotypes of rosacea and area involvement. The Rosacea Area and Severity Index (RASI) was developed to give a more nuanced evaluation of rosacea features in four facial skin areas adjusted to the relative importance of each area of the face to obtain an overall severity score. OBJECTIVES: To validate RASI against the IGA and to assess the inter- and intraobserver reliability for RASI. METHODS: Sixteen dermatologists evaluated photographs of 60 adult patients with rosacea (3 photographs per patient, one from the front and one from each side). IGA and RASI scores were performed for interobserver reliability assessment. To determine intraobserver reliability, 14 dermatologists evaluated 10 other patients twice with at least 1 week interval. RESULTS: The IGA and RASI correlated well (Spearman correlation coefficient (SCC) = 0.75, 95% confidence interval (CI) = 0.72-0.78). Interobserver reliability was moderate for RASI and poor to moderate for IGA. Reliability was strongest for rhinophyma, followed by papules/pustules and erythema, and rather weak for telangiectasia. For area scores, interobserver reliability was strongest for cheeks, followed by nose, chin and forehead. We found a moderate-to-strong intraobserver agreement both for IGA and RASI. CONCLUSIONS: We have designed a new practical tool to examine clinical severity of rosacea. RASI proved simple and reliable in scoring clinical severity of rosacea with an agreement comparable to the currently used IGA although RASI will provide a more nuanced view of the current rosacea extent and severity. We suggest that RASI is used in the daily clinical setting as well as in clinical studies assessing the efficacy of rosacea therapies.

A comprehensive epidemiological study of rosacea in Germany.

BACKGROUND: Rosacea is one of the most common skin diseases causing great distress in affected patients. For optimal patient care, epidemiological studies on disease distribution and clinical aspects are essential. OBJECTIVES: The goal of this study was to provide an updated perspective on the current state of rosacea epidemiology in Germany. MATERIALS & METHODS: A cohort of 777 rosacea patients was assessed based on a detailed online questionnaire. Information regarding patients' demographics, course and clinical presentation of rosacea, trigger factors, dermatological consultations, treatment adherence and satisfaction as well as quality of life were obtained. RESULTS: There was a very high self-reported prevalence of primary and secondary rosacea features (flushing: n = 726, 93.4%; papules/pustules: n = 613, 79.0%; telangiectasia: n = 590, 75.9%; sub jective symptoms: n = 691, 88.9%). However, these clinical findings were often underdiagnosed by the treating physicians, while changes in temperature and ultraviolet radiation were potent triggers across all patients (86.3%, 77.7%, respectively). Disease-related quality of life decreased with the number of drugs prescribed as well as with uncontrolled symptom activity, and was reduced in female patients. CONCLUSION: This study is the largest German-based assessment exclusively focusing on rosacea patients covering a variety of clinical aspects to optimize patient care.

Rosacea Treatment Satisfaction: Matching Adjusted Indirect Treatment Comparison Analysis of Metronidazole Gel or Cream vs Azelaic Acid Foam.

OBJECTIVE: To assess differences in patient-reported treatment side effects and concerns associated with azelaic acid 15% foam (AAF) vs metronidazole cream (MC) and metronidazole gel (MG). METHODS: 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. RESULTS: When compared to AAF, MG-treated patients more frequently reported concerns with treatment efficacy (54% vs 4%), application (7% vs 3%), and treatment side effects. MC-treated patients more frequently reported concerns with treatment efficacy (61% vs 5%) and dryness (8% vs 5%). AAF-treated patients more frequently reported concerns with cost of treatment compared with MG (7% vs 1%) and MC (9% vs 4%). Among patients reporting concerns, level of importance associated with these concerns was similar for AAF-treated patients compared with MG- and MC-treated patients. When compared to AAF-treated patients, MG-treated patients more frequently reported side effects of dryness (26% vs 15%) and uneven skin tone (3% vs 0%), and MC-treated patients more frequently reported side effects of burning (7% vs 3%), itching (7% vs 5%), and redness (7% vs 5%). MG- and MC-treated patients indicated greater intolerance for reported side effects than AAF-treated patients. CONCLUSIONS: MG- and MC-treated patients more frequently reported treatment concerns and side effects than AAF-treated patients, and tolerability of those side effects was higher for patients treated with AAF. While treatment cost is a more frequent concern in patients treated with AAF, these patients less frequently reported concerns with treatment efficacy and reported similar or greater tolerance to side effects than patients treated with either MC or MG. J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.3679.

Assessment of Skin Physiology Change and Safety After Intradermal Injections With Botulinum Toxin: A Randomized, Double-Blind, Placebo-Controlled, Split-Face Pilot Study in Rosacea Patients With Facial Erythema.

BACKGROUND: Botulinum toxin (BTX) has been used cosmetically with good clinical efficacy and tolerable safety. OBJECTIVE: This randomized, double-blind, split-face clinical study aimed to investigate the efficacy and safety of intradermal BTX in patients with rosacea. MATERIALS AND METHODS: Twenty-four participants were enrolled and randomly given intradermal injections of BTX and normal saline in both cheeks. Clinician Erythema Assessment (CEA) score, Global Aesthetic Improvement Scale (GAIS) score, skin hydration, transepidermal water loss (TEWL), melanin content, erythema index, elasticity, and sebum secretions were evaluated at baseline and 2, 4, 8, and 12 weeks. RESULTS: On the BTX-treated side, the CEA score significantly decreased and the GAIS score significantly increased. The erythema index decreased at Weeks 4 and 8. Skin elasticity was improved at Weeks 2 and 4 and skin hydration, at Weeks 2, 4, and 8. However, TEWL and sebum secretion did not show significant differences. CONCLUSION: Intradermal BTX injections reduced erythema and rejuvenated the skin effectively and safely in patients with rosacea.

Dose, duration, and cost: opportunities to improve use of long-term oral antibiotics for people with rosacea.

BACKGROUND: Systemic antibiotics are often used to treat rosacea and tetracyclines are the most common antibiotic prescribed; however, there is ambiguity among clinical guideline suggestions. Importantly, there is an increasing call to all clinicians to curtail antibiotic use. OBJECTIVE: To investigate the utilization and cost of long-term oral antibiotic use for the treatment of rosacea, including ocular rosacea. METHODS: This was a retrospective cohort study of MarketScan® Commercial Claims and Encounters database, from January 1, 2005 through December 31, 2014. Claim data were used to determine the duration and costs of antibiotic treatment among adults with rosacea. RESULTS: The sample included 72,411 patients. The mean (SD) duration of long-term antibiotic treatment was 87.68 (145.99) days and for patients with ocular rosacea was slightly longer, 108.34 (176.74) days [p < .0001]. The majority of antibiotic courses were shorter than 3 months (80.04%) for the entire sample and the subset with ocular rosacea (53.64% [p = .007]). LIMITATIONS: Patient adherence is uncertain and database lacks information on rosacea severity and clinical outcomes. CONCLUSIONS: The majority of oral antibiotic course durations follow guidelines. Costs of antibiotic therapy were lower for shorter courses and those utilizing generic medications; the cost-effectiveness of these modifications has not been investigated.

Fifteen Minute Test May Save 15% or More on Rosacea Treatment.

Rosacea is a common inflammatory skin condition that impacts a large portion of fair-skinned populations. The redness associated with rosacea can be a significant challenge. Brimonidine sulfate and oxymetazoline HCL were both recently approved by the FDA for the management of facial redness. These agents, however, are costly, and not all patients respond to the medication. Herein, we describe a clinical pearl that helps to optimize patient selection for the medications. This saves the patient and the health care system both time and money. J Drugs Dermatol. 2018;17(5):692-693.

Psychosocial Burden and Other Impacts of Rosacea on Patients' Quality of Life.

Rosacea is a common and chronic skin disorder with substantial impact on a patients' quality of life. Its varying phenotypic features and facial localization can adversely affect the mental health and socialization of those affected. Although there are no curative interventions, certain therapies have greater effect in improving patient quality of life. This article summarizes the associated psychosocial implications of rosacea. Several skin disease and rosacea-specific quality-of-life measures and their application in clinical care and research studies are also summarized. The recognition and management of the psychosocial impact of rosacea is critical to improving patient outcomes.

Role of Topical Oxymetazoline for Management of Erythematotelangiectatic Rosacea.

OBJECTIVE: To review and summarize topical oxymetazoline's pharmacology, pharmacokinetics, efficacy, safety, cost, and place in therapy for persistent redness associated with erythematotelangiectatic rosacea. DATA SOURCES: Literature searches of MEDLINE (1975 to September 2017), International Pharmaceutical Abstracts (1975 to September 2017), and Cochrane Database (publications through September 2017) using the terms rosacea, persistent redness, α -agonist, and oxymetazoline. STUDY SELECTION AND DATA EXTRACTION: Results were limited to studies of human subjects, English-language publications, and topical use of oxymetazoline. Relevant materials from government sources, industry, and reviews were also included. DATA SYNTHESIS: Data support the efficacy of oxymetazoline for persistent facial redness. Little study beyond clinical trials cited in the drug approval process has been conducted. Current data suggest that oxymetazoline is similar in safety and efficacy to brimonidine. Head-to-head comparisons of topical α-agonists for erythema caused by rosacea are needed. CONCLUSION: The topical α-agonist, oxymetazoline, is safe and effective for reducing persistent facial redness associated with erythematotelangiectatic subtype of rosacea. Health care practitioners selecting among treatments should consider not only the subtype of rosacea but also individual patient response, preference, and cost.

Prescription patterns and costs of acne/rosacea medications in Medicare patients vary by prescriber specialty.

BACKGROUND: Prescription patterns for acne/rosacea medications have not been described in the Medicare population, and comparisons across specialties are lacking. OBJECTIVE: To describe the medications used for treating acne/rosacea in the Medicare population and evaluate differences in costs between specialties. METHODS: A cross-sectional study was performed of the 2008 and 2010 Centers for Medicare and Medicaid Services Prescription Drug Profiles, which contains 100% of Medicare part D claims. RESULTS: Topical antibiotics accounted for 63% of all prescriptions. Patients ≥65 years utilized more oral tetracycline-class antibiotics and less topical retinoids. Specialists prescribed brand name drugs for the most common topical retinoids and most common topical antibiotics more frequently than family medicine/internal medicine (FM/IM) physicians by 6%-7%. Topical retinoids prescribed by specialists were, on average, $18-$20 more in total cost and $2-$3 more in patient cost than the same types of prescriptions from FM/IM physicians per 30-day supply. Specialists (60%) and IM physicians (56%) prescribed over twice the rate of branded doxycycline than FM doctors did (27%). The total and patient costs for tetracycline-class antibiotics were higher from specialists ($18 and $4 more, respectively) and IM physicians ($3 and $1 more, respectively) than they were from FM physicians. LIMITATIONS: The data might contain rare prescriptions used for conditions other than acne/rosacea, and suppression algorithms might underestimate the number of specialist brand name prescriptions. CONCLUSION: Costs of prescriptions for acne/rosacea from specialists are higher than those from primary care physicians and could be reduced by choosing generic and less expensive options.

Cost-Effectiveness of Ivermectin 1% Cream in Adults with Papulopustular Rosacea in the United States.

BACKGROUND: Papulopustular rosacea is a chronic skin disease involving central facial erythema in combination with papules and pustules. Papulopustular rosacea is treated with topical, systemic, or a combination of topical and systemic therapies. Currently approved topical therapies include azelaic acid gel/cream/foam twice daily (BID) and metronidazole cream/gel/lotion BID. Ivermectin 1% cream once daily (QD) is a new topical agent for the treatment of papulopustular rosacea that has been approved for the management of inflammatory lesions of rosacea and offers an alternative to current treatments. OBJECTIVE: To evaluate the cost-effectiveness of ivermectin 1% cream QD compared with current topical treatments in order to understand the cost of adding ivermectin as a treatment option that would bring additional clinical benefit for adults with papulopustular rosacea in the United States. METHODS: The cost-effectiveness of ivermectin 1% cream QD was compared with metronidazole 0.75% cream BID and azelaic acid 15% gel BID for adults in the United States with moderate-to-severe papulopustular rosacea using a Markov cohort state transition structure with 2 mutually exclusive health states (rosacea and no rosacea) and 5 phases. Patients could succeed or fail to respond to treatment and experience a relapse after treatment success. The model took a health care payer perspective (direct medical costs of topical and/or systemic therapy plus health care costs for physician and specialist visits) and used a 3-year time horizon. The model was run for a cohort of 1,000 patients. Costs (2014 U.S. dollars) and benefits (disease-free days and quality-adjusted life-years [QALYs]) were discounted at a rate of 3% per annum. Cost-effectiveness was determined by the incremental cost-effectiveness ratio (ICER) and measured in terms of incremental cost per QALY gained (estimated from health state utilities for patients with and without rosacea). Univariate and probabilistic sensitivity analyses (PSA) were conducted to assess the robustness of model outcomes. RESULTS: Compared with metronidazole 0.75% cream BID, ivermectin 1% cream QD was associated with higher costs but provided greater clinical benefit, with an ICER of $13,211 per QALY gained. For a cohort of 1,000 patients, ivermectin 1% cream QD provided an additional 72,922 disease-free days (200 years) over a 3-year period compared with metronidazole 0.75% cream BID, leading to a lower cost per disease-free day for ivermectin 1% cream QD ($4.54) compared with metronidazole 0.75% cream BID ($4.85). Ivermectin 1% cream QD was associated with lower total costs and greater clinical benefit compared with azelaic acid 15% gel BID at year 3 and dominated this treatment. After 3 years, ivermectin 1% cream QD was associated with the lowest health care costs ($62,767 compared with $73,284 for metronidazole 0.75% cream BID and $77,208 for azelaic acid 15% gel BID), reflecting a 15% reduction in physician visit costs, when compared with metronidazole 0.75% cream BID, and almost a 20% reduction, when compared with azelaic acid 15% gel BID. The univariate sensitivity analyses indicated that the results are sensitive to the time horizon selected: the longer the time horizon, the more beneficial the results for ivermectin 1% cream QD relative to the comparators, although even at 1 year, ivermectin 1% cream QD dominated azelaic acid 15% gel BID. The PSA suggested that ivermectin 1% cream QD was the most likely treatment to be cost-effective at a willingness-to-pay threshold of $15,000 and above. CONCLUSIONS: Ivermectin 1% cream QD had favorable incremental cost-effectiveness when compared with metronidazole 0.75% cream BID and dominated azelaic acid 15% gel BID in the treatment of papulopustular rosacea in the United States. Therefore, ivermectin 1% cream QD may be a good first-line treatment for papulopustular rosacea, providing additional clinical benefit at no or low additional cost. DISCLOSURES: This study was sponsored by Galderma Laboratories. The sponsor was involved in the design of the model structure but not in the collection of the data used to populate the model. Manuscript preparation was also funded by Galderma. Taieb is an investigator and advisor for Galderma. Gold is an investigator for Galderma. Feldman is a consultant and speaker for Galderma and has received grants from Galderma. Dansk and Bertranou received a research grant from Galderma to conduct this study. Dansk and Bertranou contributed to the design of the model structure, the sourcing and inputting of the data, and the interpretation of the results. Taieb, Feldman, and Gold contributed to the interpretation of the results. All authors reviewed draft versions of the manuscript and gave permission for the submission of the final version.

Erythema of Rosacea: Validation of Patient's Self-Assessment Grading Scale.

BACKGROUND: Facial erythema is a primary feature of rosacea. Currently, no validated scales exist that can accurately capture a patient's self-assessment of their own facial erythema. During phase 2 studies for brimonidine tartrate gel, a 5-point numeric rating scale was developed as a tool to allow subjects to provide an independent assessment of visible changes to the facial erythema associated with their rosacea. OBJECTIVE: The objective of this study was to validate the revised patient's self-assessment (PSA) scale and evaluate it for statistical reliability and validity in quantification of facial erythema of rosacea. METHODS: The validity of the PSA scale was evaluated by assessing the test-retest reliability, construct validity, and known-groups validity based on the data collected during a Phase 2b study on brimonidine gel for the treatment of persistent facial erythema of rosacea. RESULTS: Based on the results of this evaluation, this PSA scale demonstrated test-retest reliability, construct validity, and known-groups validity. LIMITATIONS: Study results are most generalizable to those with moderate to severe erythema. CONCLUSION: The PSA is an appropriate scale to assess facial erythema associated with rosacea.

Clinical and experimental assessment of the effects of a new topical treatment with praziquantel in the management of rosacea.

BACKGROUND: Rosacea is a common, chronic, and inflammatory skin disease. The burden imposed by this condition requires that new topical treatments be sought to enlarge the arsenal of drugs available in order to better manage this disease. OBJECTIVES: This study was conducted to carry out an in vitro/in vivo evaluation of the antimicrobial activity of 3% praziquantel (PZQ) ointment and to determine its efficacy and safety in the treatment of rosacea. METHODS: Patients with rosacea (n = 65) participated in a 16-week, randomized, single-blind pilot study of the effects of twice-daily monotherapy with 3% PZQ ointment vs. placebo (vehicle ointment). Efficacy was assessed clinically using the Investigator's Global Assessment Scale (IGAS) and the Clinical Erythema Assessment Scale (CEAS). Patients' quality of life was also determined using the Dermatology Life Quality Index (DLQI). The antimicrobial potential of 3% PZQ ointment was assessed by agar diffusion assay. RESULTS: Scores on the IGAS and CEAS showed PZQ ointment to have a statistically significant therapeutic advantage over the placebo treatment (P < 0.001). At week 16, the PZQ group demonstrated a statistically significant greater reduction in CEAS score than the placebo group (P < 0.001). Analysis of CEAS scores showed that 41.9% of patients in the PZQ group and 18.2% of those in the placebo group achieved a CEAS score equivalent to a rating of "none". Mean scores on the DLQI at baseline and at the end of the study were, respectively, 15.8 and 4.1 in the praziquantel group. The PZQ-treated group also experienced a statistically significant improvement in comparison with the placebo group at week 16 (P < 0.001). The inhibitory zone indicating the extent of antimicrobial activity of 3% PZQ ointment ranged from 6 mm to 17 mm. No serious treatment-related adverse events occurred in either treatment group. CONCLUSIONS: Use of 3% PZQ ointment twice daily for 12 weeks resulted in significantly better effects than a placebo treatment in improving rosacea and the patient's quality of life.