Scholarly journal articles and meeting abstracts authored by members of the Department of Dermatology at Henry Ford Health.
High rate of incidental detection of skin cancer following teledermatology consultation: Full body skin examination may detect more skin cancers than a referral-based approach12/1/2023 3:00 AM
Outcome Measures for the Evaluation of Treatment Response in Hidradenitis Suppurativa for Clinical Practice: A HiSTORIC Consensus Statement11/1/2023 3:00 AM
IMPORTANCE: Although several clinician- and patient-reported outcome measures have been developed for trials in hidradenitis suppurativa (HS), there is currently no consensus on which measures are best suited for use in clinical practice. Identifying validated and feasible measures applicable to the practice setting has the potential to optimize treatment strategies and generate generalizable evidence that may inform treatment guidelines.
OBJECTIVE: To establish consensus on a core set of clinician- and patient-reported outcome measures recommended for use in clinical practice and to establish the appropriate interval within which these measures should be applied.
EVIDENCE REVIEW: Clinician- and patient-reported HS measures and studies describing their psychometric properties were identified through literature reviews. Identified measures comprised an item reduction survey and subsequent electronic Delphi (e-Delphi) consensus rounds. In each consensus round, a summary of outcome measure components and scoring methods was provided to participants. Experts were provided with feasibility characteristics of clinician measures to aid selection. Consensus was achieved if at least 67% of respondents agreed with use of a measure in clinical practice.
FINDINGS: Among HS experts, response rates for item reduction, e-Delphi round 1, and e-Delphi round 2 surveys were 76.4% (42 of 55), 90.5% (38 of 42), and 92.9% (39 of 42), respectively; among patient research partners (PRPs), response rates were 70.8% (17 of 24), 100% (17 of 17), and 82.4% (14 of 17), respectively. The majority of experts across rounds were practicing dermatologists with 18 to 19 years of clinical experience. In the final e-Delphi round, most PRPs were female (12 [85.7%] vs 2 males [11.8%]) and aged 30 to 49 years. In the final e-Delphi round, HS experts and PRPs agreed with the use of the HS Investigator Global Assessment (28 [71.8%]) and HS Quality of Life score (13 [92.9%]), respectively. The most expert-preferred assessment interval in which to apply these measures was 3 months (27 [69.2%]).
CONCLUSIONS AND RELEVANCE: An international group of HS experts and PRPs achieved consensus on a core set of HS measures suitable for use in clinical practice. Consistent use of these measures may lead to more accurate assessments of HS disease activity and life outcomes, facilitating shared treatment decision-making in the practice setting.
11/1/2023 3:00 AM
Sunless tanning products have risen in popularity as the desire for a tanned appearance continues alongside growing concerns about the deleterious effects of ultraviolet radiation exposure from the sun. Dihydroxyacetone (DHA) is a simple carbohydrate found nearly universally in sunless tanning products that serves to impart color to the skin. The Food and Drug Administration (FDA), which regulates sunless tanning products as cosmetics, allows DHA for external use while maintaining that its ingestion, inhalation, or contact with mucosal surfaces should be avoided. Given its widespread use and a paucity of reviews on its safety, we aim to review the literature on the topical properties and safety profile of DHA. Available data indicate that DHA possesses only minimal to no observable photoprotective properties. In vitro studies suggest that, while DHA concentrations much higher than those in sunless tanning products are needed to induce significant cytotoxicity, even low millimolar, nonlethal concentrations can alter the function of keratinocytes, tracheobronchial cells, and other cell types on a cellular and molecular level. Instances of irritant and allergic contact dermatitis triggered by DHA exposures have also been reported. While no other side effects in humans have been observed, additional studies on the safety and toxicity of DHA in humans are warranted, with a focus on concentrations and frequencies of DHA exposure typically encountered by consumers.
Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations11/1/2023 3:00 AM
BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking.
OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo.
METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings.
RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed.
CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.
Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the International Vitiligo Task Force Part 1: towards a new management algorithm11/1/2023 3:00 AM
BACKGROUND: The treatment of vitiligo can be challenging and depends on several factors such as the subtype, disease activity, vitiligo extent, and treatment goals. Vitiligo usually requires a long-term approach. To improve the management of vitiligo worldwide, a clear and up-to-date guide based on international consensus with uniform stepwise recommendations is needed.
OBJECTIVES: To reach an international consensus on the nomenclature and to develop a management algorithm for the diagnosis, assessment, and treatment of vitiligo.
METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence of topics included in the algorithms. A survey was utilized to resolve remaining issues among a core group of eight experts. Subsequently, the unanimous recommendations were finalized and validated based on further input from the entire group during two live meetings.
RESULTS: The algorithms highlight the importance of shared decision-making. Dermatologists are encouraged to provide patients with detailed explanations of the prognosis and expected therapeutic outcomes based on clinical examination. The treatment goal should be discussed and clearly emphasized to patients given the different approaches for disease stabilization and repigmentation. The evaluation of disease activity remains a cornerstone in the tailor-made approach to vitiligo patients.
CONCLUSIONS: These new treatment algorithms are intended to guide clinical decision-making in clinical practice. Promising novel therapies for vitiligo are on the horizon, further highlighting the need for reliable outcome measurement instruments and greater emphasis on shared decision-making.
Hyperpolarization-activated cyclic nucleotide-gated cation channel 3 promotes HCC development in a female-biased manner10/31/2023 3:00 AM
Sex differences in hepatocellular carcinoma (HCC) development are regulated by sex and non-sex chromosomes, sex hormones, and environmental factors. We previously reported that Ncoa5(+/-) mice develop HCC in a male-biased manner. Here we show that NCOA5 expression is reduced in male patient HCCs while the expression of an NCOA5-interacting tumor suppressor, TIP30, is lower in female HCCs. Tip30 heterozygous deletion does not change HCC incidence in Ncoa5(+/-) male mice but dramatically increases HCC incidence in Ncoa5(+/-) female mice, accompanied by hepatic hyperpolarization-activated cyclic nucleotide-gated cation channel 3 (HCN3) overexpression. HCN3 overexpression cooperates with MYC to promote mouse HCC development, whereas Hcn3 knockout preferentially hinders HCC development in female mice. Furthermore, HCN3 amplification and overexpression occur in human HCCs and correlate with a poorer prognosis of patients in a female-biased manner. Our results suggest that TIP30 and NCOA5 protect against female liver oncogenesis and that HCN3 is a female-biased HCC driver.
Comments on: "Risk factors and novel predictive model for metastatic cutaneous squamous cell carcinoma: a population-based analysis"10/1/2023 3:00 AM
10/1/2023 3:00 AM
Hematopoietic stem cell transplantation is increasing in frequency with graft-versus-host disease affecting many recipients. When the skin is involved, biopsy is routinely performed but often does not aid in definitive diagnosis. Here, we examine a cohort of 32 patients for potential biomarkers that can aid in the diagnosis of graft-versus-host disease. Neither blood short tandem repeat testing or neutrophil-lymphocyte ratios were predictive of rash etiology in hematopoietic stem cell transplant patients. However, skin short tandem repeat testing showed promise as a predictor in a small minority of cases in this cohort.
Tapinarof Cream 1% Once Daily for the Treatment of Plaque Psoriasis: Case Photography of Clinical Outcomes from Three Phase 3 Trials10/1/2023 3:00 AM
Tapinarof cream 1% (VTAMA(®); Dermavant Sciences, Inc.) is a non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration (FDA) to treat plaque psoriasis in adults and under investigation for the treatment of psoriasis in children down to 2 years of age, and for atopic dermatitis in adults and children down to 2 years of age. The PSOARING phase 3 clinical trial program evaluated tapinarof cream 1% once daily (QD) in adults with mild to severe plaque psoriasis for up to 52 weeks (NCT03956355, NCT03983980, NCT04053387).
Here we present case photography documenting outcomes in the PSOARING trials. Cases illustrate various outcomes across different body areas, including responses meeting the formal FDA-mandated regulatory endpoint of a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) and a decrease of at least 2 points from baseline at week 12, meaningful clinical improvement not meeting this formal endpoint, patient-reported outcomes, and pre-specified adverse events of special interest (AESIs). Tapinarof cream 1% QD demonstrated rapid and highly statistically significant efficacy, with improvements in disease activity and quality of life. In addition, a high rate (40.9%; n = 312/763) of complete disease clearance (PGA = 0) was achieved, and improvements exceeding National Psoriasis Foundation treatment goals were demonstrated. After first achieving complete disease clearance (PGA = 0), patients treated with tapinarof experienced an approximately 4-month remittive effect off therapy. Incidence and severity of folliculitis and contact dermatitis AESIs were generally mild or moderate, localized to the site of application, and associated with low discontinuation rates. Medical images are of importance in trials of dermatologic therapies to inform clinical decision-making and enhance patient assessment. Tapinarof cream 1% QD is efficacious and well tolerated in patients with mild to severe plaque psoriasis, with clinically relevant improvements seen early in the course of treatment.
Clinicaltrials.gov numbers: NCT03956355, NCT03983980, NCT04053387.
9/30/2023 3:00 AM
Efficacy and Safety of Clascoterone Cream 1% in Patients with Acne vulgaris across Subgroups Defined By Demographic Characteristics6/1/2023 3:00 AM
Objectives: Clascoterone cream 1% is approved for the treatment of acne vulgaris in patients aged ≥12 years. Pooled efficacy and safety data stratified by age and sex from two randomized, double-blind, vehicle-controlled Phase 3 studies (CB-03-01/25 and CB-03-01/26) and an open-label long-term extension study (CB-03-01/27) are presented.
Methods: Patients with moderate-to-severe acne were randomized 1:1 to twice-daily treatment of the face with clascoterone or vehicle for 12 weeks (W); all patients continuing into the open-label extension study applied clascoterone for up to 9 additional months. Efficacy was assessed in the intention-to-treat (ITT) population for proportion of randomized patients achieving an Investigator’s Global Assessment score of 0 or 1 (IGA 0/1) with a ≥2-point reduction from baseline. Safety was assessed from treatment-emergent adverse events (TEAEs) in all treated patients.
Results: Of 709/712 patients aged ≥12 years originally randomized to clascoterone/vehicle, 63.9%/60.4% were female, and the mean ± standard deviation (SD) age was 19.8 ± 6.1/19.5 ± 6.1 years; there were only 11/13 male patients aged ≥25 years, and no data are shown for this subgroup. Among patients in the ITT population randomized to clascoterone/vehicle, 17.2%/3.9% (12–17 years; P <0.0001), 24.4%/9.8% (≥18 years; P <0.0001), and 31.5%/10.8% (females ≥25 years; P = 0.002) achieved IGA 0/1 by W12; 45.6%, 54.0%, and 44.4% of extension study patients aged 12–17, ≥18, and females ≥25 years, respectively, achieved IGA 0/1 after 12 months applying clascoterone. Frequency of TEAEs through W12 in clascoterone/vehicle-treated patients was 10.8%/14.2%, 11.5%/11.6%, and 9.6%/12.9% for ages 12–17, ≥18, and females ≥25 years, respectively.
Conclusions: Clascoterone efficacy and safety were maintained in adolescent and adult patients, including female patients aged ≥25 years.
CO125 Efficacy of Clascoterone Cream 1% for up to 12 Months in Patients ≥9 Years of Age with Acne vulgaris: Results from a Long-Term Extension Study6/1/2023 3:00 AM
Objectives: Clascoterone cream 1% is approved for the treatment of acne vulgaris in patients aged ≥12 years. Efficacy data from an open-label extension study are presented.
Methods: The open-label, multicenter extension study (CB-03-01/27) enrolled male and female patients aged ≥9 years who completed one of the 12-week Phase 3 trials (CB-03-01/25 and CB-03-01/26) in patients with moderate-to-severe acne vulgaris. All patients applied 1% clascoterone cream twice daily to the face for 9 months; in the extension study, patients with truncal acne could also treat affected areas of the shoulders, chest, and/or back. Total time on clascoterone was up to 12 months for patients originally randomized to clascoterone in the Phase 3 trials. A 5-point Investigator’s Global Assessment (IGA; 0, clear; 4, severe) was performed at extension Days 29, 85, 183, and 274; clascoterone treatment could be discontinued if IGA was 0 or 1 (IGA 0/1) and reinstated if/when acne worsened. Efficacy was analyzed in the intention-to-treat (ITT) population.
Results: The ITT population included 609 patients, of whom 251 patients were treated for truncal acne. At baseline/Day 29/85/183/274, the proportion of ITT patients achieving facial IGA 0/1 was 9.9%/8.5%/10.1%/17.3%/29.8% and the proportion of ITT patients achieving truncal IGA 0/1 was 4.8%/17.1%/20.7%/25.9%/31.5%. In the ITT population, 539/417/304/123 patients used clascoterone for a total of 3/6/9/12 months. By total time on clascoterone, 13.1%/18.9%/39.2%/56.1% of ITT patients achieved facial IGA 0/1 and 13.6%/37.6%/43.4%/59.2% of ITT patients achieved truncal IGA 0/1 after 3/6/9/12 months on clascoterone treatment.
Conclusions: Clascoterone cream 1% maintained a favorable efficacy profile for up to 12 months in patients aged ≥9 years with acne vulgaris.
PCR234 Impact of Draining Tunnels on Patient- and Physician-Reported Burden in Patients with Hidradenitis Suppurativa (HS)6/1/2023 3:00 AM
Objectives: Hidradenitis suppurativa (HS) has one of the greatest impacts on quality of life (QoL) of any dermatological disease. This study explored the patient- and physician-reported burden of HS with and without draining tunnels (dT).
Methods: This study used real-world data collected (November 2020–April 2021) from physician surveys, patient surveys, and medical records as part of the Adelphi HS Disease Specific Programme (DSP™). Validated patient-reported outcomes used were the HS QoL (HiSQOL) score, the work productivity and activity impairment questionnaire, and the EQ5D-visual analog scale (EQ5D-VAS). Results are presented descriptively. Patients with missing values for a variable were removed from all analyses involving that variable.
Results: Of 580 moderate-to-severe HS patients included in this study, 46% (n=264) had dT. For patients with and without dT, mean age of 38.9 and 33.3 years, and 55.3% and 57.6% were female, respectively. From physician-reported data, patients with dT were more likely to experience a great impact on their lives than patients without dT (51.1% vs. 31.3%). Physicians agreed (agreement of 7–10 on a 1–10 scale) that patients with dT were more likely to experience a negative impact on their mental health (66.3% vs. 48.7%) and sexual function (65.5% vs. 50.3%). Patients with dT reported higher ratings on a pain scale from 7–10 (10 indicating worst pain, 28.9% vs. 11.0%), and were more likely to experience worse mood, reduced ability to work, negative feelings about the futures, and a deteriorated financial situation. Overall, patients with dT reported worse QoL (HiSQOL, 22.3 vs. 16.2), greater work impairment (34.0% vs. 25.9%), and worse general health (EQ5D-VAS, 62.9 vs. 72.0).
Conclusions: In this group, patients with dT experienced a more substantial disease burden than patients without dT; this provides insight into the impact of dT and highlights the need for effective treatment strategies.
5/1/2023 3:00 AM
The 2022 mpox outbreak affected 84,318 individuals in 110 countries. Mpox is transmitted by multiple modalities, including direct contact, respiratory droplets, and fomites among others. Identifying skin lesions aids prompt diagnosis. Variation in initial skin lesion location is not well understood; it is hypothesized that mode of transmission may determine primary inoculation site and subsequent clinical presentation. This study sourced healthcare provider-reported data from the AAD/ILDS Dermatology COVID-19, Mpox, and Emerging Infections Registry to explore factors related to the location of the first skin lesion in mpox cases. Out 119 mpox cases,115 had primary lesion location data. 97% were male with a median age of 37. Most (83/115, 72%) patients had first skin lesions in the genito-anal area, and 32/115 (27%) had lesions elsewhere or had morbilliform rash. 74% of males had the first lesion in the genito-anal region compared to females (25%, p=0.03). Males in same-sex relationships had ano-genital lesions more often than men in other relationships (77% vs. 44%, p=0.03). The type of mpox exposure was also associated with first lesion location: 83% of patients who contracted mpox from a spouse or other sexual contact had ano-genital lesions as compared to a non-sexual contact (0%, p=<0.01). This analysis characterized factors associated with the first mpox skin lesion location, which can aid healthcare providers in diagnosis and shed light on transmission. This data suggests that type of exposure and mode of transmission may be associated with primary lesion location; patients who contracted mpox from sexual contact were more likely to have ano-genital lesions.
5/1/2023 3:00 AM
In 2022, mpox virus spread globally with 99% of cases in non-endemic countries. People living with HIV (PLHIV) are disproportionally affected, often with more severe clinical features and outcomes. The AAD/ILDS Dermatology COVID-19, Monkeypox (mpox), and Emerging Infections registry captured mpox cases from 13 non-endemic countries in a de-identified REDCap registry. We aimed to examine cutaneous symptomatology and outcomes in cases of mpox in PLHIV. Of 119 reported cases, 44 were PLHIV (35%). Cases were 98% male, with a median age of 38 years, located in Europe (57%) and the U.S. (39%). Nearly half of PLHIV reported skin lesions as their initial sign (45%), and 43 (98%) reported skin lesions during illness. The primary initial lesion locations were peri-anal (34%) and genito-inguinal (34%). Co-infection with other sexually transmissible infections (STI) was more common in PLHIV, 57% vs. 38% in all-registry cases (p<0.01). The most common co-infections were gonorrhea, syphilis, and chlamydia. Time to resolution was 17 days, 3 days shorter than all-registry cases, which may be due to higher use of Tecovirimat in PLHIV (36% vs. 25% in all-registry cases; p<0.01). There were no differences in the frequency of hospitalization or scarring. One death was reported. Overall, cutaneous lesion count was similar in PLHIV and all-registry cases. Lesion location was more frequently reported in the peri-anal and genito-inguinal regions. Sample size was insufficient to detect differences in length of infection, hospitalization, or scarring in PLHIV. Co-infections were more common in PLHIV, highlighting a need for co-testing for STIs during mpox evaluation.
Impact of acne on social functioning, emotional functioning, and activities of daily living (ADL) among patients with moderateto- severe non-nodular acne vulgaris (AV) administered sarecycline in real-world community practices across the US (PROSES Study)4/1/2023 3:00 AM
Background: Understanding of AV impact on patient Health-related quality of life (HRQoL) is still evolving.
Objective: The key objective of this analysis was to evaluate patientperceived impact of AV on emotional/social functioning and ADL through a novel Expert Panel Questionnaire (EPQ), among AV patients administered sarecycline, an oral narrow-spectrum, tetracycline-derived antibiotic, in real-world community practices across the US.
Methods: A single-arm, prospective cohort study (PROSES) was conducted with moderate-to-severe non-nodular AV patients aged 9 years or older who were prescribed sarecycline. Primary endpoint included 11-item EPQ responses (completed by patients (>12years) and caregivers (for patients 9-11 yrs) at Week 12 and corresponding change from baseline (CFB)). All items were scored on a five-point adjectival response scale (score=0/1 (never/rarely, not at all/slightly/a little), score=2 (some of the time, somewhat), and score=3/4 (most of the time/all of the time, moderately/ extremely, quite a bit/very much). The EPQs related to AV impact on emotional functioning (EPQ 1-4), social functioning (EPQ 5-7), and ADL (EPQ 8-11) were formulated based on dermatology expert panel consensus using modified Delphi method. CFB in proportion of patients reporting score=0/1 (no/least impact) for EPQ items at Week-12 were analyzed.
Results: A total of 253 AV patients completed the study (adults: 60.08%; pediatric: 39.92%; female: 66.40%). CFB in patients reporting score=0/1 (no/least impact) for each EPQ item increased statistically significantly (p<0.0001) except for EPQ10. In emotional functioning domain, CFB=31.62 percent for EPQ1 on patients' mood/anger; CFB= 28.85 percent, 20.95 percent, 38.74 percent respectively for EPQ2, EPQ3, EPQ4 on hopelessness/worries about skin. In social functioning domain, CFB=23.72 percent for EPQ5 on patients' social media/selfie activity, CFB=22.93 percent for EPQ6 on impact on real-life plans, and CFB=21.34 percent for EPQ7 on efforts to hide AV. In ADL domain, CFB=15.02 percent for EPQ8 on picked-on/judged due to AV, CFB=13.83 percent for EPQ9 on ability to reach future goals, and CFB=0.99 percent for EPQ10 on parent understanding of AV concerns (for patients<18yrs), and CFB=18.18 percent for EPQ11 on sleep impact.
Conclusion: Patients reporting no/least AV burden in emotional functioning, social functioning, and ADL significantly increased in patients with moderate-to-severe AV who were administered sarecycline for 12 weeks.
Evaluation of an SPF50 sunscreen containing photolyase and antioxidants for its antiphotoaging properties4/1/2023 3:00 AM
Background: Skin exposure to ultraviolet radiation (UVR) causes DNA damage, which can lead to mutagenesis, carcinogenesis, cellular death, and photoaging. Signs of photoaging include wrinkling, erythema, skin laxity, uneven skin texture, and hyperpigmentation. Photolyase is an exogenous DNA repair enzyme that can restore DNA integrity when applied topically to human skin. Antioxidants also play a key role in reducing UVR-associated molecular damage.
Objective: To assess the efficacy of a mineral-based sunscreen containing 10.7% zinc oxide (SPF50) with the active ingredients photolyase, antioxidants (Vitamin E and Peptide Q10), and peptides in both protecting against and repairing visible signs of photoaging.
Methods: In an open-label, single-center, 12-week study, patients aged 35-65 years and Fitzpatrick Skin Types II-IV applied the sunscreen daily for 84 days. VISIA photography was performed at baseline as well as 6- and 12-week follow-ups. At each visit, the investigator and subject evaluated clinical photoaging parameters including overall photodamage, fine lines/wrinkles, coarse lines/ wrinkles, skin tone evenness, tactile roughness, and radiance.
Results: The Investigator Global Aesthetic Improvement Scale (IGAIS) found that 63 percent of patients showed improvement at Week 6 and 81 percent at Week 12. The Subject Global Aesthetic Improvement Scale (SGAIS) showed 58% percent and 62.5 percent of patients reported the appearance of their skin was improved at Week 6 and 12, respectively. Overall, there was a statistically significant improvement in skin radiance as well as improvement in overall facial aesthetics reported by both investigators and subjects.
Conclusion: A mineral-based SPF50 sunscreen containing photolyase, antioxidants, and peptides is effective at repairing some clinical signs of photoaging.
Durability of efficacy and safety of roflumilast cream 0.3% in adults with chronic plaque psoriasis from a 52-Week, Phase 2 open-label safety trial4/1/2023 3:00 AM
Background: Roflumilast cream is a potent phosphodiesterase 4 inhibitor recently approved in the United States for treatment of plaque psoriasis with no limitations on duration of use. An open-label trial was conducted to evaluate long-term safety (52 weeks) of once-daily roflumilast cream (NCT03764475). This abstract presents data on durability of response as measured by the percentage of patients with an Investigator Global Assessment (IGA) score of Clear or Almost Clear, percentage improvement in Psoriasis Area Severity Index (PASI) score, and reduction in body surface area (BSA) affected.
Methods: Patients who completed a parent, Phase 2b, 12-week randomized controlled trial could continue on open-label roflumilast cream 0.3% (Cohort-1, n=230), and patients naïve to roflumilast were also enrolled (Cohort-2, n=102). All psoriasis lesions (except scalp) were treated, including face and intertriginous areas for up to 52 weeks. If affected, palms and soles were treated, but not evaluated towards any efficacy assessments. Median duration of response was determined using the Kaplan-Meier method.
Results: With cumulative treatment up to 64 weeks in Cohort-1 and 52 weeks in Cohort-2, long-term safety and tolerability were consistent with the 12-week, Phase 2b study. Overall, 73.5 percent of patients completed the study; 3.9 percent discontinued due to adverse events (AE) and 0.9 percent discontinued due to lack of efficacy. Treatment-related AEs were reported in 2.7 percent patients; none were deemed serious. Investigator tolerability assessments at each visit demonstrated 99 percent of patients rated “no evidence of irritation.” At Week 52, IGA Success (demonstrating Clear/Almost Clear plus 2-grade improvement from baseline) was achieved by 34.8 percent of patients in Cohort-1 and 39.5 percent in Cohort-2. Of patients in Cohort-2, 40 percent of patients achieved IGA success at Week 12. IGA Clear/Almost Clear was achieved by 46.8 percent of patients across both cohorts at Week 12 and consistent through Week 52 (44.8%). Similarly, a 60.5 percent mean PASI improvement and 60.1 percent mean BSA improvement from baseline were observed at Week 12 and consistent through Week 52 (59.4% and 63.3%, respectively). Of the 185 patients who achieved IGA Clear/Almost Clear during the open-label trial, the median durability of IGA of Clear/ Almost Clear was 10 months (40.1 weeks). Among patients who achieved an IGA of Clear or Almost Clear, 50 percent maintained Clear or Almost Clear status for at least 10 months.
Conclusion: In this long-term safety study, roflumilast cream was well tolerated with a safety profile consistent with the parent Ph2b trial, and effectively maintained clear/almost clear skin with no tachyphylaxis observed.
Comparison of investigator global assessment (IGA) and patient's global assessment (ptGA) of acne vulgaris among patients with moderate-to-severe non-nodular acne vulgaris (AV) administered sarecycline in community practices across the US: Analysis of PROSES study results4/1/2023 3:00 AM
Background: The objective of this analysis was to compare facial IGA and patient's Global assessment (ptGA) of AV at baseline and Weeks 4, 8 and 12, among AV patients administered sarecycline in community practices across the US.
Methods: A single-arm, prospective cohort study (PROSES) was conducted with moderateto- severe non-nodular AV patients older than 9 years who were prescribed sarecycline in realworld community practices in the US Facial IGA of patient's AV status was reported by the study clinician and ptGA of AV was collected as part of validated ASIS questionnaire; both measures used a five-point adjectival response scale of 0 (clear), 1 (almost-clear), 2 (mild), 3 (moderate), 4 (severe), and collected at baseline and Weeks 4, 8 and 12. Proportion of patients with clear/almost clear AV per IGA and ptGA were analyzed for all study timepoints.
Results: A total of 253 AV patients completed the study (adults 60.08%; pediatric 39.92%; female: 66.40%; Caucasian/white: 68.38%, African-American: 8.70%; Other-races: 22.92%; moderate AV: 86.56%; severe AV: 13.44%). At baseline, 0 percent and 4.74 percent were clear/ almost clear, per IGA and ptGA respectively. At Week-4, 9.09 percent and 29.18 percent were clear/almost-clear, per IGA and ptGA respectively. At Week-8, 33.99 percent and 41.84 percent were clear/almost-clear, per IGA and ptGA respectively. At Week-12, 58.89 percent and 59.29 percent were clear/almost-clear, per IGA and ptGA respectively. Increase in proportion of patients with clear/almost clear over time, as measured by IGA and ptGA were respectively statistically significant at p<0.0001.
Conclusion: Within the study cohort administered sarecycline, a narrow-spectrum, tetracyclinederived antibiotic, for 12 weeks, proportion of patients with clear/almost clear facial AV (as measured by clinicians and patients respectively) increased significantly, with almost six out of 10 patients achieving clear/almost clear facial AV at Week 12.
Tapinarof cream 1% once daily for plaque psoriasis: improvements in quality of life and clinical efficacy in two pivotal Phase 3 trials3/13/2023 3:00 AM
Background: Tapinarof cream 1% once daily (QD) demonstrated statistically significant efficacy versus vehicle and was well-tolerated in adults with mild to severe plaque psoriasis in PSOARING 1 and 2, two 12-week, Phase 3 trials. In addition, significantly greater improvements in Dermatology Life Quality Index (DLQI) change from baseline at Week 12 were observed with tapinarof versus vehicle.
Objective: To evaluate correlations between the DLQI and clinical efficacy as assessed by Physician Global Assessment (PGA) and Psoriasis Area and Severity Index (PASI) in PSOARING 1 and 2.
Methods: Patients in PSOARING 1 and 2 were randomized to tapinarof or vehicle for 12 weeks. The DLQI is a 10-item scale where each item is rated on a 4-point scale from zero (not at all) to three (very much); lower scores indicate higher quality of life (QoL). Efficacy was evaluated using PGA and PASI. Spearman rank correlations evaluated correlations between changes in efficacy and QoL from baseline at Week 12. Analyses used observed cases and were based on the intention-to-treat population.
Results: 683 tapinarof and 342 vehicle-treated patients from PSOARING 1 and 2 were included in the analyses. At baseline, 79.2 to 83.9 percent of patients had a PGA of 3 (moderate), mean PASI of 8.9-9.1, and mean DLQI of 8.2-8.7 (moderate impact of disease on QoL) in PSOARING 1 and 2. Mean change in DLQI from baseline at Week 12 was -5.0 vs -3.0 (P<0.0001) and -4.7 vs. -1.6 (P<0.0001), with tapinarof versus vehicle in each trial, respectively. The minimal clinically important difference in DLQI of 4 was exceeded at Week 12 in the tapinarof groups. A significantly higher proportion of patients achieved a DLQI of 0 or 1 at Week 12 in the tapinarof groups versus vehicle: 47.4 percent vs 23.3 percent (P<0.0001) and 44.9 percent vs 16.1 percent (P<0.0001) in each trial, respectively; statistical significance in favor of tapinarof was observed as early as Week 4. Improvements in DLQI in the tapinarof groups at Week 12 were statistically correlated with improvements in PGA (0.28 and 0.29, P<0.0001) and PASI (0.28 and 0.40, P<0.0001) in each trial, respectively.
Conclusion: Tapinarof demonstrated rapid, clinically meaningful, and statistically significant improvements in clinical efficacy and patientreported QoL. A large percentage of tapinaroftreated patients achieved a DLQI of 0 or 1, i.e., no negative effects of disease on QoL. Correlations between improvements in DLQI and clinical efficacy measures suggest that, beyond clinical improvements captured by the PASI and PGA, other important factors such as mental/emotional wellbeing and satisfaction with treatment contribute to the considerable overall improvement in QoL observed in these trials.