IGAxBSA composite for assessing disease severity and response in patients with atopic dermatitis.

BACKGROUND: Accurate assessment of atopic dermatitis (AD) severity is critical when initiating and monitoring therapy. Use of existing research tools such as the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD) is complex and time-consuming in clinical practice. A previous analysis found the product of validated Investigator's Global Assessment (vIGA) and affected body surface area (BSA) to be an accurate and practical tool for routine assessment of paediatric AD. OBJECTIVE: To evaluate the IGAxBSA composite as an alternative to EASI or SCORAD for assessment of AD disease severity and disease responsiveness. METHODS: The relationship between IGAxBSA, EASI and SCORAD was assessed in a post hoc analysis of pooled data from the dupilumab clinical trial programme in adult and paediatric patients with moderate-to-severe AD who had received dupilumab or placebo, with or without topical corticosteroids (TCS). The trials are registered at ClinicalTrials.gov and EudraCT: LIBERTY AD SOLO 1 (NCT02277743, 2014-001198-15), LIBERTY AD SOLO 2 (NCT02277769, 2014-002619-40), LIBERTY AD SOLO-CONTINUE (NCT02395133, 2014-003384-38), LIBERTY AD CHRONOS (NCT02260986, 2013-003254-24), LIBERTY AD CAFÉ (NCT02755649, 2015-002653-35), LIBERTY AD ADOL (NCT03054428, 2015-004458-16), LIBERTY AD PEDS (NCT03345914, 2016-004997-16), LIBERTY AD OLE (NCT01949311, 2013-001449-15) and LIBERTY AD PEDS OLE (NCT02612454, 2015-001396-40). RESULTS: Using datapoints from pooled dupilumab randomized controlled trials (n = 3473) and open-label extension trials (n = 3045), we found that IGAxBSA correlated well with EASI and SCORAD, irrespective of treatment group and race (white, Asian, black). IGAxBSA correlated better with objective measures (EASI, SCORAD) than with patient- or caregiver-reported subjective measures. IGAxBSA correlated strongly with EASI and SCORAD in assessing disease change over time (r = 0·90, r = 0·76, respectively; P < 0·0001), and concordance between IGAxBSA-50/75/90 and EASI-50/75/90 was excellent (88-94%). CONCLUSIONS: IGAxBSA is a valid alternative for assessment of AD disease severity and response over time, compared with EASI or SCORAD in patients with AD, irrespective of race.

Use of an alternative method to evaluate erythema severity in a clinical trial: difference in vehicle response with evaluation of baseline and postdose photographs for effect of oxymetazoline cream 1·0% for persistent erythema of rosacea in a phase IV study.

BACKGROUND: Once-daily topical oxymetazoline cream 1·0% significantly reduced persistent facial erythema of rosacea in trials requiring live, static patient assessments. OBJECTIVES: To evaluate critically the methodology of clinical trials that require live, static patient assessments by determining whether assessment of erythema is different when reference to the baseline photograph is allowed. METHODS: In two identically designed, randomized, phase III trials, adults with persistent facial erythema of rosacea applied oxymetazoline or vehicle once daily. This phase IV study evaluated standardized digital facial photographs from the phase III trials to record ≥ 1-grade Clinician Erythema Assessment (CEA) improvement at 1, 3, 6, 9 and 12 h postdose. RESULTS: Among 835 patients (oxymetazoline n = 415, vehicle n = 420), significantly greater proportions of patients treated with oxymetazoline vs. vehicle achieved ≥ 1-grade CEA improvement. For the comparison between phase IV study results and the original phase III analysis, when reference to baseline photographs was allowed while evaluating post-treatment photographs, the results for oxymetazoline were similar to results of the phase III trials (up to 85.7%), but a significantly lower proportion of vehicle recipients achieved ≥ 1-grade CEA improvement (up to 29.7% [phase 4] vs. 52.3% [phase 3]; P<0.001). In the phase IV study, up to 80·2% of patients treated with oxymetazoline achieved at least moderate erythema improvement vs. up to 22·9% of patients treated with vehicle. The association between patients' satisfaction with facial skin redness and percentage of erythema improvement was statistically significant. CONCLUSIONS: Assessment of study photographs, with comparison to baseline, confirmed significant erythema reduction with oxymetazoline on the first day of application. Compared with the phase III trial results, significantly fewer vehicle recipients attained ≥ 1-grade CEA improvement, suggesting a mitigated vehicle effect. This methodology may improve the accuracy of clinical trials evaluating erythema severity.

A global perspective on the epidemiology of acne.

Acne is estimated to affect 9.4% of the global population, making it the eighth most prevalent disease worldwide. Epidemiological studies have demonstrated that acne is most common in postpubescent teens, with boys most frequently affected, particularly with more severe forms of the disease. This paper aims to provide an update on the epidemiology of acne worldwide. Recent general and institutional studies from around the world have shown that the prevalence of acne is broadly consistent globally (with the exception of specific populations, which are discussed). However, this review highlights that there is a wide range of disparate outcome measures being applied in epidemiology studies, and we emphasize the need to develop a widely accepted, credible, standard assessment scale to address this in the future. In addition we discuss special populations, such as those devoid of acne, as well as the impact of potential determinants of acne on disease epidemiology.

Correlation of photographic images from the Leeds revised acne grading system with a six-category global acne severity scale.

BACKGROUND: Few global acne grading systems include individualized assessments of chest and back as well as face. The Leeds revised acne grading system is based on photographic images while the Comprehensive Acne Severity Scale (CASS) is based on textual descriptions. There exists an unmet need for a global scale based on both text and photos. PURPOSE: Our objective was to evaluate the correspondence of severity grades from descriptive text (CASS grades) for each Leeds image. METHODS: Twenty-three dermatologists independently graded 56 photos of face, chest and back of varying acne severity using CASS. Photographs were randomly presented from the The Leeds revised acne grading system (n = 31) and from acne patients of the corresponding author (n = 25). For each Leeds photo, rater responses for CASS grades were transformed into median, coefficient of variation and percentiles. RESULTS: High rater agreement (≥75%) was observed for Leeds facial inflammatory 2 (CASS 3), 4 (CASS 4), 6 (CASS 4), 9-12 (all CASS 5); Leeds facial comedonal A (CASS 2); Leeds chest 7 and 8 (both CASS 5); and Leeds back 7 and 8 (both CASS 5). Lowest coefficients of variance were observed in Leeds facial inflammatory 4, 9, 10, 11; Leeds facial comedonal A; Leeds chest 7 and 8; and Leeds back 8. Conclusions Leeds photos, by inadequately portraying facial acne grades 1 (almost clear) and 2 (mild) and back and chest grades 1-4 (almost clear to severe), cannot accurately represent the spectrum of severity in a six-category global acne scale. Accordingly, there is a current need for images that correspond to a categorical acne scale.

Adapalene 0.1% and benzoyl peroxide 2.5%: a novel combination for treatment of acne vulgaris.

Topical products commonly used to treat acne include retinoids and antimicrobials, due to their effects on different components of pathogenesis. Accordingly, a fixed combination of adapalene 0.1% and benzoyl peroxide (BPO) 2.5% was developed (Epiduo, Galderma) and was approved by the US FDA in December 2008 for the treatment of acne. The superior efficacy of this combination was demonstrated in 2 large randomized controlled trials. This paper reviews the evidence for efficacy and tolerability of the combination of the retinoid adapalene 0.1% and BPO 2.5%, a once-daily gel formulation for the treatment of acne.

New developments in hormonal therapy for acne.

Oral contraceptives (OCs) are a valuable option for the treatment of women with acne. The use of OCs can be considered across the spectrum of acne disease severity in women. In Canada, three preparations are approved for mild-to-moderate acne, and a fourth is indicated for severe acne. These formulations contain estrogen in the form of ethinyl estradiol and a progestin. In Canada, the most recently approved OC is ethinyl estradiol 0.03 mg and drospirenone 3mg (Yasmin, Bayer). With the accumulating evidence on the efficacy and safety of drospirenone-containing hormonal preparations, this formulation provides dermatologists with a new treatment option for acne and other hyperandrogenic disorders.

Psychosocial impact of acne vulgaris: evaluating the evidence.

This paper reviews current evidence presented by recent studies on the impact of acne on psychosocial health. Study methodologies, including case-control and cross-sectional surveys, have demonstrated psychological abnormalities including depression, suicidal ideation, anxiety, psychosomatic symptoms, including pain and discomfort, embarrassment and social inhibition. Effective treatment of acne was accompanied by improvement in self-esteem, affect, obsessive-compulsiveness, shame, embarrassment, body image, social assertiveness and self-confidence. Acne is associated with a greater psychological burden than a variety of other disparate chronic disorders. Future studies with a longitudinal cohort design may provide further validation of the causal inference between acne and psychosocial disability provided by the current literature.

Clindoxyl gel for the treatment of acne vulgaris.

Clindoxyl Gel (Stiefel) is a combination of 1% clindamycin phosphate and 5% benzoyl peroxide in a gel vehicle that is well tolerated and more efficacious than either active agent alone or the vehicle in reducing lesion counts and improving global scores in patients with moderate acne. It was approved for once daily use in Canada in November 2001.

Randomized placebo-controlled trial of metronidazole 1% cream with sunscreen SPF 15 in treatment of rosacea.

BACKGROUND: Rosacea is a photoaggravated dermatosis responsive to treatment with topical and oral antibiotics. A formulation combining metronidazole 1% cream with sunscreen SPF 15 was developed for the treatment of rosacea. OBJECTIVE: The objective of this study was to determine the safety and efficacy of a formulation combining metronidazole 1% cream with sunscreen SPF 15 in the treatment of moderate to severe rosacea. METHODS: One hundred and twenty patients with moderate to severe rosacea were enrolled for a randomized, placebo-controlled (vehicle containing sunscreen with SPF 15), double-blind study. Study cream was applied twice daily to the entire face over a 12-week period. RESULTS: Treatment with metronidazole 1% cream with sunscreen SPF 15 resulted in significant improvement (p <0.05) in inflammatory lesion count, erythema and telangiectasiae scores, and investigator and patient global assessment scores compared with baseline and placebo. Adverse reactions related to study medication were typically mild, occurred at the site of application, and were reversible. There was no difference between the safety profiles of metronidazole 1% cream with sunscreen SPF 15 and placebo. CONCLUSIONS: The combined topical formulation of metronidazole 1% cream with sunscreen SPF 15 was an effective, well-tolerated topical agent for the treatment of moderate to severe rosacea.