Investigator's Global Assessment Scale Research Articles

Effect of Dead Sea Climatotherapy on Psoriasis; A Prospective Cohort Study.

Background: Dead Sea climatotherapy (DSC) is a treatment option for psoriasis in Denmark. However, the response to DSC has not been particularly well studied.Aim: We sought to determine effectiveness and response duration of DSC on psoriasis-related outcome parameters.Methods: Eighteen patients participated in a 4-week treatment program in Ein Gedi in Israel. Treatment, consisting of sun exposure and bathing, was individualized.Results: DSC was associated with a mean 13.0-point reduction (88%) in Psoriasis Area and Severity Index and a mean reduction of 2.3 (76.7%) on the 5-point Investigator's Global Assessment Scale. Furthermore, patients' quality of life improved measured by the Dermatology Quality of Life Index and EuroQol 5D index values. The mean time from treatment end to reappearance of visible skin symptoms was 93.8 days (SD: 62.5, range: 31–219 days).Conclusions: Our results confirm that DSC has an immediate effect on skin manifestations and improves quality of life, but long-term disease control is not observed.

Treating Psoriasis With Halobetasol Propionate and Tazarotene Combination: A Review of Phase II and III Clinical Trials.

Objective: To review phase II and III clinical trial data to evaluate the efficacy and safety of the halobetasol propionate/tazarotene (HP/TAZ) combination lotion (Duobrii), a medication approved by the Food and Drug Administration in April 2019 for adults with plaque psoriasis. Data Sources: A systematic search (January 2005 to July 2019) of MEDLINE (PubMed) and EMBASE databases was performed using the terms halobetasol, tazarotene, halobetasol/tazarotene, Duobrii, and IDP-118. Study Selection and Data Extraction: Relevant English-language articles reporting on phase II and phase III clinical trials were included. Data from the individual trials were extracted independently and then cross-checked to ensure accuracy. Data Synthesis: HP/TAZ was safe and efficacious compared with HP alone, TAZ alone, or vehicle. More patients achieved treatment success, described as a ≥2-grade improvement on Investigator Global Assessment Scale, over 8 weeks of treatment and at the 4-week follow-up after treatment cessation. The most common adverse events were dermatitis, pain, and pruritus, which occurred more often in the TAZ groups compared with the HP/TAZ cohorts. Relevance to Patient Care and Clinical Practice: The once-daily HP/TAZ combination lotion simplifies psoriasis treatment and may facilitate adherence, which may improve psoriasis outcomes. Conclusions: HP/TAZ combination lotion is efficacious and safe for plaque psoriasis treatment, with more patients achieving end points and fewer side effects than in HP, TAZ, or vehicle-treated controls. Drug synergy may play a role. Importantly, patient adherence to a once-daily combinational therapy is likely to contribute to efficacy.

Myths, Perceptions and Practices in Acne: A Study on Adolescents and Young Adults.

Background and aim: Acne vulgaris is a worldwide disease, affecting 85% of adolescents and young adults. Psychological burden of the disease can be profound and may even exceed its physical impact. Adolescents often seek information from a variety of sources, which contributes misinformation and misconceptions. The aim of the present study was to investigate perspectives and attitudes of adolescents and young adults towards acne. Material and Methods: A total of 318 consecutive patients with acne vulgaris (236 female, 82 male) were prospectively enrolled over a period of 4 months. Following a thorough dermatological examination, patients were graded according to Investigator's Global Assessment scale for disease severity. Patients were asked to respond a 28-item self-administered questionnaire, which consisted of questions on beliefs, perceptions and practices of the patients towards acne. Results: 63.5% of the patients considered acne as a ‘must be treated disease’ and 96.5% believed that treatment should be given by a dermatologist. 84.6% of the patients presumed that dietary changes may reduce or prevent acne lesions, while 95% regarded some dietary factors as aggravating. Female patients more frequently assumed acne as a hormonal disease. Patients with university education considered high water intake and increased fruit and vegetable consumption as ameliorating factors for acne. Conclusion: The overall knowledge about acne was found to be poor. These data confirm the need for public awareness and education on acne.

Conjunctivitis in patients with atopic dermatitis treated with dupilumab is associated with higher baseline serum levels of immunoglobulin E and thymus and activation-regulated chemokine but not clinical severity in a real-world setting

To the Editor: Conjunctivitis has been observed as an adverse event in patients with atopic dermatitis (AD) receiving dupilumab. Its incidence rate ranges from 8.6% to 21.44% in clinical trials,1Akinlade B. Guttman-Yassky E. de Bruin-Weller M. et al.Conjunctivitis in dupilumab clinical trials.Br J Dermatol. 2019; 181: 459-473Crossref PubMed Scopus (178) Google Scholar whereas real-world data have shown an even higher prevalence.2Uchida H. Kamata M. Mizukawa I. et al.Real-world effectiveness and safety of dupilumab for the treatment of atopic dermatitis in Japanese patients: a single-centre retrospective study.Br J Dermatol. 2019; 181: 1083-1085Crossref PubMed Scopus (25) Google Scholar We analyzed our data to explore practical predictors of later development of conjunctivitis in patients with AD initiating dupilumab in a real-world setting. The study included adult patients with AD who had been treated with dupilumab in our hospital for more than 3 months as of October 1, 2019. Other inclusion criteria were the same as those described in our previous report.2Uchida H. Kamata M. Mizukawa I. et al.Real-world effectiveness and safety of dupilumab for the treatment of atopic dermatitis in Japanese patients: a single-centre retrospective study.Br J Dermatol. 2019; 181: 1083-1085Crossref PubMed Scopus (25) Google Scholar Baseline clinical severity, patents’ history of conjunctivitis, and results from laboratory blood tests were compared between patients who developed conjunctivitis and those who did not. Data on 57 Japanese adult patients (49 men, 8 women) with AD were analyzed. The mean ± standard deviation age at starting dupilumab was 38.1 ± 11.8 years. Conjunctivitis was observed in 22.8% (13 of 57) of patients after starting dupilumab. The mean time to develop conjunctivitis after beginning dupilumab was 5.3 ± 3.9 weeks. Conjunctivitis developed at a higher frequency after starting dupilumab in patients who had a history of conjunctivitis at baseline than in those who did not. Patients in whom conjunctivitis occurred after starting dupilumab had significantly higher serum levels of thymus and activation-regulated chemokine (TARC) and immunoglobulin E (IgE) at baseline than those who did not (Fig 1). The cutoff values at baseline were 3342 pg/mL (sensitivity, 69.23%; specificity, 79.55%) for TARC and 11,200 IU/mL (sensitivity, 76.92%; specificity, 69.77%) for IgE, with moderate accuracy. No significant differences were observed between them in clinical severity, including Investigator's Global Assessment, affected body surface area, the Eczema Area and Severity Index, and results of other laboratory blood tests. Clinical trials have demonstrated that baseline disease-related factors, including AD severity, prior conjunctivitis history, and certain biomarkers (TARC, IgE, eosinophils), are associated with an increased incidence of conjunctivitis.1Akinlade B. Guttman-Yassky E. de Bruin-Weller M. et al.Conjunctivitis in dupilumab clinical trials.Br J Dermatol. 2019; 181: 459-473Crossref PubMed Scopus (178) Google Scholar It is reasonable, because levels of certain biomarkers, such as TARC, IgE, and eosinophils, increase with AD severity.3Beck L.A. Thaci D. Hamilton J.D. et al.Dupilumab treatment in adults with moderate-to-severe atopic dermatitis.N Engl J Med. 2014; 371: 130-139Crossref PubMed Scopus (879) Google Scholar, 4Hamilton J.D. Suarez-Farinas M. Dhingra N. et al.Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis.J Allergy Clin Immunol. 2014; 134: 1293-1300Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar, 5Guttman-Yassky E. Bissonnette R. Ungar B. et al.Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis.J Allergy Clin Immunol. 2019; 143: 155-172Abstract Full Text Full Text PDF PubMed Scopus (244) Google Scholar However, our real-world data revealed that only baseline serum TARC and IgE levels were significantly higher in patients who developed conjunctivitis and that a history of conjunctivitis and eosinophils showed its tendency, whereas baseline clinical severity did not demonstrate any association with incidence of conjunctivitis. Even in data from clinical trials, the difference in the incidence of conjunctivitis between patients with AD with a baseline score of 3 on the 5-point Investigator's Global Assessment scale and those with a baseline of 4 was quite small in CHRONOS (NCT02260986) (0.06 vs 0.09 per 100 patient-years) and in CAFÉ (NCT02755649) (0.22 vs 0.23).1Akinlade B. Guttman-Yassky E. de Bruin-Weller M. et al.Conjunctivitis in dupilumab clinical trials.Br J Dermatol. 2019; 181: 459-473Crossref PubMed Scopus (178) Google Scholar Distinguishing the subtle differences in disease severity of AD among patients with moderate to severe AD (not including mild AD) is difficult for physicians. Our study underscores that among those parameters, serum levels of TARC and IgE could reflect subtle differences in predisposition for conjunctivitis more accurately than the disease severity of AD evaluated by physicians, especially among patients with moderate to severe AD, indicating that these objective parameters are useful as practical predictors of later development of conjunctivitis.

A topical regimen improves skin healing and aesthetic outcomes when combined with a radiofrequency microneedling procedure.

Novel topical products formulated using tri- and hexapeptide technology (TriHex Technology® ; Alastin Skincare® , Inc) are used to clear the extracellular matrix, stimulate neocollagenesis and elastogenesis, decrease inflammation, and accelerate the epidermal healing process. This study assessed the efficacy of two topical tri- and hexapeptide-containing products pre- and post-treatment with radiofrequency (RF) microneedling of the photoaged neck with respect to healing and aesthetic outcomes. In this open-label, nonrandomized study, eligible subjects underwent one screening visit, one RF microneedling procedure and follow-up visits on post-treatment Days 3, 7, 30, and 90. Subjects were instructed to apply one product to the neck for 2weeks prior to treatment and 7days post-treatment. On post-treatment Day 7, subjects switched to the other product until the end of the study. At each visit, subject and investigator questionnaires were completed and standardized digital images were obtained. Female subjects (N=10) with a mean age of 51.3years (range, 44-59years) completed the study. All subjects achieved statistically significant improvements in Investigator Global Assessment scales at post-treatment Day 90 and reported improvement in all Skin Quality Assessments. Among Subjective Tolerability Assessments, all post-treatment reports of tingling and burning resolved by Day 3. 90% of stinging resolved by Day 3 with 100% resolving by Day 7. 40% of subjects had minimal itching on Day 3 which resolved by Day 7. Among the Investigator Post-treatment Tolerability Assessments, edema resolved in all subjects by Day 3 and erythema settled between Day 3 and Day 7. Pre- and post-treatment use of topical products formulated with tri- and hexapeptide technology appears to hasten healing and complement aesthetic outcomes associated with RF microneedling of the neck.

SIG1459: A novel phytyl‐cysteine derived TLR2 modulator with in vitro and clinical anti‐acne activity

Cutibacterium (formerlyPropionibacterium acnes) is a major contributor to the pathogenesis of acne. C.acnes initiates an innate immune response in keratinocytes via recognition and activation of toll-like receptor-2 (TLR2), a key step in comedogenesis. Tetramethyl-hexadecenyl-cysteine-formylprolinate (SIG1459), a novel anti-acne isoprenylcysteine (IPC) small molecule, is shown in this study to have direct antibacterial activity and inhibit TLR2 inflammatory signalling. In vitro antibacterial activity of SIG1459 against C.acnes was established demonstrating minimal inhibitory concentration (MIC=8.5μmol\L), minimal bactericidal concentration (MBC=16.1μmol\L) and minimal biofilm eradication concentration (MBEC=12.5μmol\L). To assess SIG1459's anti-inflammatory activity, human keratinocytes were exposed to C.acnes and different TLR2 ligands (peptidoglycan, FSL-1, Pam3CSK4) that induce pro-inflammatory cytokine IL-8 and IL-1α production. Results demonstrate SIG1459 inhibits TLR2-induced IL-8 release from TLR2/TLR2 (IC50 =0.086μmol\L), TLR2/6 (IC50 =0.209μmol\L) and IL-1α from TLR2/TLR2 (IC50 =0.050μmol\L). To assess the safety and in vivo anti-acne activity of SIG1459, a vehicle controlled clinical study was conducted applying 1% SIG1459 topically (n=35 subjects) in a head-to-head comparison against 3% BPO (n=15 subjects). Utilizing the Investigator Global Assessment scale for acne as primary endpoint, results demonstrate 1% SIG1459 significantly outperformed 3% BPO over 8weeks, resulting in 79% improvement as compared to 56% for BPO. Additionally, 1% SIG1459 was well tolerated. Thus, SIG1459 and phytyl IPC compounds represent a novel anti-acne technology that provides a safe dual modulating benefit by killing C.acnes and reducing the inflammation it triggers via TLR2 signalling.

Use of an Investigator's Global Assessment Scale to Evaluate Disease Severity in Patients swith Epidermolysis Bullosa Simplex

Abstract not available. Disclosures: Study supported by Castle Creek Pharma. Copyright SKIN 2018

Application of Analytic Technique Using Green Light Parallel-Polarized Light Images in Various Skin Diseases.

Application of Analytic Technique Using Green Light Parallel-Polarized Light Images in Various Skin Diseases.

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

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. 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. 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. 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 week16 (P<0.001). The inhibitory zone indicating the extent of antimicrobial activity of 3% PZQ ointment ranged from 6mm to 17mm. No serious treatment-related adverse events occurred in either treatment group. Use of 3% PZQ ointment twice daily for 12weeks resulted in significantly better effects than a placebo treatment in improving rosacea and the patient's quality of life.