Triple Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% for Acne: Efficacy and Safety from a Pooled Phase 3 Analysis.

INTRODUCTION: A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data. METHODS: In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated. RESULTS: At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12. CONCLUSIONS: The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04214639 and NCT04214652.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Guidelines of care for the management of acne vulgaris.

BACKGROUND: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. OBJECTIVE: The objective of this study was to provide evidence-based recommendations for the management of acne. METHODS: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. LIMITATIONS: Analysis is based on the best available evidence at the time of the systematic review. CONCLUSIONS: These guidelines provide evidence-based recommendations for the management of acne vulgaris.

Prevalence and Demographics of Truncal Involvement Among Acne Patients: Survey Data and a Review of the Literature.

Background: Truncal acne is frequently underdiagnosed despite affecting around half of those with facial acne. The objective was to provide an overview of the literature on the incidence of truncal acne according to age, gender, and acne severity. Methods: A narrative review of data from recent large surveys and a literature search in PubMed on the incidence of truncal acne across subgroups of age, gender, and acne severity. Results: The prevalence of truncal acne alone was low, ranging from <1% to 14%, but approximately 30 to 60 percent of individuals with facial acne also had truncal acne depending on the population. In an online survey in the United States of 2,000 respondents aged between 14 -29 years with self-reported active facial and/or truncal acne, the incidence of truncal acne was lower in the 14-20 years subgroup than in the 21-29 years subgroup (49% vs 54%). The incidence of truncal acne was similar in both males and females, while 46 percent of respondents with self-declared clear and mild acne indicated having truncal involvement compared to 60 percent of those with moderate or severe acne. Limitations: Online surveys have inherent limitations, such as self-reporting and potential confounders. Conclusion: Data suggests that patients with both facial and truncal involvement have earlier onset of acne and more severe acne. Additional adverse psychological impact may arise from having the impression that the disease is spreading and becoming more severe. Raising awareness of truncal acne prevalence and demographics could improve its clinical management to reduce the negative psychological impact.

Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug.

BACKGROUND: A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. OBJECTIVES: We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. METHODS: In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. RESULTS: A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. CONCLUSIONS: Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017).

Nonantibiotic Properties of Tetracyclines in Rosacea and Their Clinical Implications.

Rosacea is one of the most common inflammatory skin diseases in the United States, with a complex pathophysiology. One of the major components of the pathophysiology of rosacea is an abnormal immune detection and response to stimuli. Tetracyclines and their derivatives, including minocycline and doxycycline, have anti-inflammatory properties independent of their antibacterial activity that correlate with certain aspects of the pathophysiology, and these drugs are often used by dermatologists to treat rosacea. Biological actions of tetracyclines correlating with rosacea include anti-inflammatory and antioxidative activities, inhibitory effects on angiogenesis, and proteolysis. The objective of this review is to re-establish the current understanding of tetracyclines and their mechanism of action as they relate to the pathophysiology and treatment of rosacea for clinicians. This includes reviewing the inflammatory aspects of rosacea that correlate with the known nonantibiotic properties of tetracyclines and providing the most up-to-date clinical evidence supporting the use of tetracyclines to treat rosacea. Given the evolving and multifactorial nature of pathophysiology, this review offers clinicians a unified picture that includes research on the links between rosacea pathophysiology and clinical presentation, the nonantibiotic properties of tetracyclines that relate to pathophysiologic pathways in rosacea, and the potential for clinical application of tetracyclines in rosacea therapy.

Formulation and Profile of FMX101 4% Minocycline Topical Foam for the Treatment of Acne Vulgaris.

FMX101 4% minocycline is a hydrophobic, topical foam formulation of minocycline recently approved by the United States Food and Drug Administration (FDA) for the treatment of non-nodular inflammatory lesions in moderate-to-severe acne vulgaris. It was developed to harness the anti-inflammatory and antibiotic activity of minocycline while minimizing potentially serious systemic adverse events associated with oral delivery. The composition and profile of this novel treatment have yet to be described. This article discusses the components of the foam-based product and the rationale for their selection. It reviews microbiologic data for FMX101 4% and presents previously unpublished data regarding sebum penetration, minocycline permeation, and disposition into skin structures. The effects of FMX101 4% were compared with those of several commercially available acne preparations to determine how the FMX101 4% formulation affects the physical properties of model human sebum in vitro. The hydrophobic formulation of FMX101 4% was found to lower the melting temperature of model human sebum below that of normal skin temperature, decreasing its viscosity. FMX101 4% achieved high concentrations of minocycline in the sebaceous appendage, while minimizing permeation beyond the dermal layer. Finally, this article summarizes efficacy and safety data for FMX101 4% from three Phase III studies (FX2014-04, FX2014-05, and FX2017-22). FMX101 4% appeared to be safe, effective, and well tolerated for the treatment of non-nodular inflammatory lesions in moderate-to-severe acne vulgaris. In conclusion, the topical formulation of minocycline in FMX101 4% represents a unique treatment for acne vulgaris and a viable alternative to oral administration.

Novel Polymeric Tazarotene 0.045% Lotion for Moderate-to-Severe Acne: Pooled Phase 3 Analysis by Race/Ethnicity.

Background: Acne vulgaris and inflammation-associated sequelae are highly prevalent in black and Hispanic populations. In a phase 2 study, a novel polymeric emulsion formulation of tazarotene 0.045% lotion had relatively fewer adverse events than tazarotene 0.1% cream, but with comparable efficacy. The objective was to evaluate tazarotene 0.045% lotion by race and ethnicity in the pivotal trials. Methods: In two phase 3, double-blind, 12-week studies (NCT03168334; NCT03168321), participants with moderate-to-severe acne were randomized 1:1 to tazarotene 0.045% lotion or vehicle lotion (N=1,614). This pooled, post hoc analysis included subsets of participants that self-identified as white (n=1191) or black (n=262) and Hispanic (n=352) or non-Hispanic (n=1262). Coprimary endpoints were inflammatory/noninflammatory lesion counts and treatment success (defined as at least a 2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 'clear' or 'almost clear'). Treatment-emergent adverse events (TEAEs) and cutaneous safety and tolerability were evaluated. Results: At week 12, tazarotene 0.045% lotion led to significantly greater percent reductions in inflammatory and noninflammatory lesions compared with vehicle in white, Hispanic, and non-Hispanic participants (P<0.05, all). Black participants had significantly greater reductions in noninflammatory lesions following treatment with tazarotene 0.045% versus vehicle (P<0.05). Treatment success rates in all subpopulations were higher with tazarotene 0.045% lotion (29.4-34.1%) versus vehicle (16.4-23.1%). TEAE rates were similar across tazarotene-treated groups and most were mild-to-moderate in severity. The incidence of hyperpigmentation decreased in black tazarotene-treated participants from baseline to week 12. Conclusions: Tazarotene 0.045% lotion demonstrated efficacy and was well tolerated across racial and ethnic subpopulations in this pooled analysis. J Drugs Dermatol. 2020;19(7) doi:10.36849/JDD.2020.5125.

Safety and efficacy of halobetasol propionate lotion 0.01% in the treatment of moderate to severe plaque psoriasis: a pooled analysis of 2 phase 3 studies.

Potent topical corticosteroids (TCSs) are the mainstay of psoriasis treatment. Safety concerns have limited use to 2 to 4 weeks. The objective of our study was to investigate the safety and efficacy of once-daily halobetasol propionate (HP) lotion 0.01% in moderate to severe plaque psoriasis through 2 multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (N=430). Participants were randomized (2:1) to HP lotion 0.01% or vehicle once daily for 8 weeks, followed by 4 weeks of follow-up. The primary efficacy assessment was treatment success (at least a 2-grade improvement in baseline investigator global assessment [IGA] score and a score of 0 [clear] or 1 [almost clear]). Additional assessments included improvement in psoriasis signs and symptoms, body surface area (BSA), and a composite score of IGA×BSA. Safety and treatment-emergent adverse events (AEs) were evaluated throughout. We found that HP lotion 0.01% demonstrated statistically significant superiority over vehicle as early as week 2 and also was superior in reducing psoriasis signs and symptoms and BSA involvement.

Safety and Efficacy of Escalating Doses of Ingenol Mebutate for Field Treatment of Actinic Keratosis on the Full Face, Full Balding Scalp, or Chest.

Background: Actinic keratosis (AK) can affect large skin areas. Ingenol mebutate (IngMeb) gel (0.015% and 0.05%) is approved for topical treatment of AK in a single contiguous area of ~25 cm2.

Objective: The study sought to determine the maximum tolerated dose (MTD), efficacy, and tolerability of IngMeb applied to AK on a contiguous area less than equal to 250 cm2.

Methods: Part 1 determined the MTD of IngMeb at 7 concentrations for 2 or 3 days. Part 2 assessed efficacy and tolerability at the MTD and one dose lower for 2 or 3 days vs vehicle.

Results: Four dosing regimens with an acceptable benefit-to-risk ratio were identified: 0.018% and 0.027% once daily for 2 or 3 days. Complete clearance at 8 weeks was achieved by 21.3% to 39.1% of IngMeb-treated patients vs 0% to 3.2% treated with vehicle. Composite local skin response scores peaked on the day after the last application, rapidly declined, and were near baseline at 2 weeks. Adverse events were predominantly mild or moderate.

Limitations: The study evaluated a limited number of doses in a population of only white patients.

Conclusion: IngMeb gel was effective and well tolerated as field treatment of AK on the full face, full scalp, and up to 250 cm2 on the chest.

J Drugs Dermatol. 2017;16(5):438-444.

Transapical transcatheter aortic valve replacement in patients with or without prior coronary artery bypass graft operation.

BACKGROUND: Transapical approach (TA) is an established access alternative to the transfemoral technique in patients undergoing transcatheter aortic valve replacement (TAVR) for treatment of symptomatic aortic valve stenosis. The impact of prior coronary artery bypass grafting (CABG) on clinical outcomes in patients undergoing TA-TAVR is not well defined. METHODS: A single center retrospective cohort analysis of 126 patients (male 41%, mean age 85.8 ± 6.1 years) who underwent TA balloon expandable TAVR (Edwards SAPIEN, SAPIEN XT or SAPIEN 3) was performed. Patients were classified as having prior CABG (n = 45) or no prior CABG (n = 81). Baseline clinical characteristics, in-hospital, 30-day, 6 months and one-year clinical outcomes were compared. RESULTS: Compared to patients without prior CABG, CABG patients were more likely to be male (62.2 vs. 29.6%, p < 0.001) with a higher STS score (11.66 ± 5.47 vs. 8.99 ± 4.19, p = 0.003), history of myocardial infarction (55 vs. 21.1%, p < 0.001), implantable cardioverter defibrillator (17.8 vs. 3.7%, p = 0.017), left main coronary artery disease (42.2 vs. 4.9%, p < 0.001), and proximal left anterior descending coronary artery stenosis (57.8 vs. 16%, p < 0.001). They also presented with a lower left ventricular ejection fraction (%) (42.3 ± 15.3 vs. 54.3 ± 11.6, p < 0.01) and a larger effective valve orifice area (0.75 ± 0.20 cm2 vs. 0.67 ± 0.14 cm2, p = 0.025). There were no intra-procedural deaths, no differences in stroke (0 vs. 1.2%, p = 1.0), procedure time in hours (3.50 ± 0.80 vs. 3.26 ± 0.86, p = 0.127), re-intubation rate (8.9 vs. 8.6% p = 1.0), and renal function (highest creatinine value 1.73 ± 0.71 mg/ml vs.1.88 ± 1.15 mg/ml, p = 0.43). All-cause mortality at 6 months was similar in both groups (11.4, vs. 17.3% p = 0.44), and one-year survival was 81.8 and 77.8% respectively (p = 0.51). On multivariate analysis, the only factor significantly associated with one-year mortality was prior history of stroke (HR, 2.76; 95% CI, 1.06-7.17, p = 0.037). CONCLUSION: Despite the higher baseline clinical risk profile, patients with history of prior CABG undergoing TA-TAVR had comparable in-hospital, 6 months and one-year clinical outcomes to those without prior CABG.

Efficacy and Safety of Once-Daily Dapsone Gel, 7.5% for Treatment of Adolescents and Adults With Acne Vulgaris: First of Two Identically Designed, Large, Multicenter, Randomized, Vehicle-controlled Trials.

BACKGROUND: Treatment of acne vulgaris (acne) with dapsone gel, 5% requires twice-daily dosing, and some patients may not adhere to this regimen.
OBJECTIVE: The objective of this study was to assess the efficacy and safety of a new, once-daily formulation of dapsone gel, 7.5%, with a 50% higher dapsone concentration, versus vehicle over 12 weeks in patients with acne.
METHODS: This 12-week, randomized, double-blind, vehicle-controlled, multicenter clinical trial enrolled patients with moderate acne aged 12 years and older with 20 to 50 inflammatory lesions and 30 to 100 noninflammatory lesions on the face, and an acne grade of 3 (moderate) on the Global Acne Assessment Score (GAAS). Patients were randomized to receive topical dapsone gel, 7.5% or vehicle once daily for 12 weeks. Investigators assessed GAAS success rate (proportion of patients with GAAS of 0 or 1) and percent change from baseline in inflammatory, noninflammatory, and total lesions.
RESULTS: The intent-to-treat population comprised 2102 patients, 1044 in the dapsone gel, 7.5% group and 1058 in the vehicle group. At week 12, 29.9% of patients in the dapsone gel, 7.5% group and 21.2% in the vehicle group (P<.001) had GAAS success. Mean inflammatory lesions decreased by 55.5% and 49.0%, noninflammatory lesions decreased by 44.4% and 38.4%, and total lesions decreased by 48.7% and 42.4% in the dapsone gel, 7.5% and vehicle groups (all P<.001), respectively, at week 12. The incidence of adverse events was similar in the dapsone gel, 7.5% (19.1%) and vehicle (20.6%) groups. Most events in both groups were mild or moderate in severity. Most patients receiving dapsone gel, 7.5% and vehicle had a severity rating of "none" for stinging/burning, dryness, scaling, and erythema scales at all time points.
CONCLUSIONS: Dapsone gel, 7.5% applied topically once daily is an effective, safe, and well-tolerated treatment for acne.

J Drugs Dermatol. 2016;15(5):553-561.

Improvement in Extensive Moderate Plaque Psoriasis With a Novel Emollient Spray Formulation of Betamethasone Dipropionate 0.05.

BACKGROUND: A novel formulation of 0.05% betamethasone dipropionate in an emollient spray vehicle (DFD-01) was developed to deliver steroid to the skin layers most affected by psoriasis. OBJECTIVE: To compare the efficacy and safety of DFD-01 to its vehicle for the treatment of moderate plaque psoriasis over 4 weeks. METHODS: Two Phase 3 trials enrolled adults with moderate psoriasis (Investigator Global Assessment [IGA]=3; 10-20% body surface area [BSA]) and randomized them 2:1 to DFD-01 or Vehicle. Products were applied twice daily to affected areas for 28 days. Treatment success was defined as an IGA=0 or 1 and ≥ 2-grade improvement from baseline. Primary endpoint was the proportion of subjects achieving treatment success at day 15. RESULTS: Moderate psoriasis subjects were enrolled in Study 1 (174 DFD-01; 87 Vehicle) and Study 2 (182 DFD-01; 95 Vehicle). Mean BSA was 13-14%. Treatment success was achieved in significantly more subjects using DFD-01 than Vehicle at day 15 in both Study 1 (P<0.001) and Study 2 (P=0.002), and at day 29 (both studies P<0.001). Treatment success with DFD-01 was significant at day 8 in Study 1 (P=0.003) but not in Study 2 (P=0.156). Erythema, scaling, and plaque elevation scores of target lesions were significantly reduced as early as day 4 with DFD-01. Adverse events were similar between groups, with no increase between 2 and 4 weeks. CONCLUSION: These studies demonstrate DFD-01's excellent efficacy and safety for the treatment of extensive psoriasis (10-20% BSA). DFD-01 achieved treatment success in significantly more subjects than Vehicle after 2 and 4 weeks of treatment, and showed early onset of action with improved signs of erythema, scaling and elevation of target lesions after 4 days of treatment. This medium potency formulation provides a safe and effective choice for topical steroid treatment of psoriasis.

Guidelines of care for the management of acne vulgaris.

Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence.

Current Understanding of Seborrheic Keratosis: Prevalence, Etiology, Clinical Presentation, Diagnosis, and Management.

Seborrheic keratosis (SK) is among the most common cutaneous lesions, affecting some 83 million Americans. Biologically benign, SK lesions do not require removal for medical reasons unless histologic confirmation of the clinical diagnosis is required or the lesions are traumatized and/or become symptomatic. These macular or popular pigmented lesions are often of cosmetic concern to patients. In addition, their natural history of gradually increasing in size, thickness, and/or pigmentation often serves as the impetus compelling patients to present to a dermatologist for evaluation and skin cancer screening; SK is diagnosed and managed primarily by dermatologists. Data regarding SK prevalence and management from a survey of 594 practicing, board-certified dermatologists are summarized herein: Dermatologists report they diagnose an average of 155 patients per month with SK. Among SK patients presenting to dermatologists, 33% have more than 15 SK lesions and 67% have 15 or fewer SK lesions. On average, dermatologists treat 43% of their SK patients to remove lesions. Cryosurgery is the most common removal method. Other commonly employed removal methods include shave excision, electrodessication, curettage or a combination of these. While these procedures can be used to remove SK lesions effectively, each has potential drawbacks and careful patient selection is required to optimize cosmetic results particularly in skin of color patients and patients with thick or numerous lesions. While there is great interest from both patients and providers in a topical non-invasive treatment for SK, no effective topical therapeutic agent has been developed, and this remains an area of unmet need.

Clinical study results of desoximetasone spray, 0.25% in moderate to severe plaque psoriasis.

Two Phase 3, double-blind, randomized, vehicle-controlled parallel studies evaluated the efficacy and safety of desoximetasone spray 0.25%, a super-potent topical corticosteroid, twice daily vs vehicle spray twice daily for 28 days in adult patients with moderate to severe plaque psoriasis. At baseline and throughout the study, the severity of disease for the psoriatic lesions was assessed using the Physician Global Assessment (PGA) score and a target lesion was assessed using the Total Lesion Severity Score (TLSS). A designated psoriatic plaque lesion was selected as the target lesion upon enrollment and evaluated throughout the study to determine the TLSS. To qualify for study entry, the subject needed to exhibit a PGA score of 3 (moderate) or 4 (severe) for overall disease severity, and a target lesion with an area of at least 5 cm(2) that achieved a combined score TLSS of >=7, with a plaque elevation score of >=3 (at least moderate). The mean % BSA affected by psoriasis ranged from 13%-17% at baseline. In both Phase 3 studies, a statistically significantly greater percentage of subjects in the desoximetasone spray 0.25% compared to vehicle group achieved both Clinical Success and Treatment Success at Day 28. These results, which were the primary efficacy variables, demonstrated superior efficacy in the active study group for both overall improvement of plaque psoriasis (by PGA) and in the individual psoriasis lesion (by TLSS) designated at baseline as the most severely involved plaque (target lesion). Assessment of secondary efficacy variables in both Phase 3 studies showed that subjects receiving desoximetasone Spray 0.25% twice daily exhibited statistically significantly mean changes from Baseline to Day 28 in PGA, TLSS, and % BSA affected when compared to subjects receiving vehicle spray twice daily. Tolerability and safety were assessed at all study visits. No statistically significant differences were observed between study arms and no major safety signals related to AEs were noted. No stinging and burning were reported with the spray formulation. This Class I topical corticosteroid has shown to be safe and efficacious in moderate to severe plaque psoriasis.

Messages from molecules: deciphering the code.

Acne therapy should be based on pathogenesis. Current mainstays of therapy include topical retinoids, antibiotics, and benzoyl peroxide. Newer research has shown that inflammation may precede comedo formation. Gene array analysis of acne lesions has elucidated newer inflammatory mediators that may become future targets for therapeutic development.

A multi-center, open-label study to evaluate the safety and efficacy of a sequential treatment regimen of clobetasol propionate 0.05% spray followed by Calcitriol 3 mg/g ointment in the management of plaque psoriasis.

BACKGROUND: Psoriasis is a hyperproliferative and inflammatory skin disorder that affects roughly 2 percent of the worldwide population. Clobetasol propionate is the most common corticosteroid used to treat moderate-to-severe psoriasis but the potential for side effects limits its long-term use. Topical vitamin D, which is used to treat mild-to-moderate psoriasis, has been shown to be safe when used daily for up to 52 weeks. To date, very few studies exist evaluating the use of clobetasol propionate in a regimen with calcitriol to manage moderate-to-severe disease over time. OBJECTIVES: To evaluate the efficacy and assess safety of a regimen of sequential topical treatments with clobetasol propionate 0.05% spray for up to four weeks followed by calcitriol 3 µg/g ointment for eight weeks in the management of moderate-to-severe plaque psoriasis. METHODS: This was a multi-center, open-label study in subjects aged 18-80 years with moderate-to-severe plaque psoriasis at baseline. Subjects applied clobetasol propionate 0.05% spray twice daily for up to four weeks. At the end of four weeks, if the subject's overall disease severity (ODS) was assessed as clear, almost clear, mild or moderate, subjects started treatment with calcitriol 3 µg/g ointment twice daily. Twice-daily treatment with calcitriol 3 µg/g ointment continued for eight weeks (until week 12) or unless the subject's ODS was assessed as severe or returned to the baseline score, at which time it was discontinued. Subjects were evaluated at baseline and at weeks 2, 4, 8 and 12. RESULTS: Of the 305 subjects enrolled, 170 subjects completed the full 12-week study with no major protocol deviations and comprised the per-protocol (PP) study population. Treatment success, defined as at least one grade improvement in ODS at week 12 compared to baseline, was achieved in 84.1 percent of subjects. The percent body surface area affected (% BSA) decreased from 7.1 percent at baseline to 3.9 percent at week 12 (P<0.001). The sequential treatment regimen was well tolerated with no unexpected adverse events. Most reported adverse events and cutaneous irritations were mild in severity. CONCLUSIONS: The results of this study indicate that the 12-week regimen of clobetasol propionate 0.05% spray treatment for four weeks immediately followed by an eight-week treatment phase with calcitriol 3 µg/g ointment is efficacious and safe for the management of moderate-to-severe plaque psoriasis.

Long-term safety and efficacy study of adapalene 0.3% gel.

The efficacy and safety of adapalene 0.1% gel in the treatment of acne vulgaris has been demonstrated in multiple controlled clinical trials. A higher concentration formulation, adapalene 0.3% gel, has been developed to provide a broader range of treatment options for acne management. Phase 3 clinical studies have demonstrated the superior efficacy of adapalene 0.3% gel compared to adapalene 0.1% gel and its vehicle at the end of a 12-week treatment period. The goal of this study was to evaluate the long-term safety of adapalene 0.3% gel in subjects treated once daily for 52 weeks, with a secondary objective to evaluate long-term efficacy. Subjects 12 years of age or older (N=551) with acne vulgaris participated in a multicenter, open-label study of the long-term (up to 52 weeks) efficacy and safety of once-daily applications of adapalene 0.3% gel. Of those enrolled, 167 subjects completed 12 months of treatment. Expected signs and symptoms of local cutaneous irritation (erythema, dryness, scaling, and stinging/burning) were mostly mild or moderate, with mean tolerability scores below 1 (mild) at all time points for the parameters assessed. Treatment-related, dermatologic adverse events were experienced by 21% of subjects and dry skin, skin discomfort, and scaling were reported by 10.5%, 8.3% and 3.3% of subjects, respectively. Most of the adverse events reported occurred in the first quarter of treatment. Adverse events were mostly mild to moderate in severity. Subjects treated with adapalene 0.3% gel for 52 weeks achieved a >75% median reduction in total, inflammatory, and noninflammatory lesions in this open-label study by the end of the treatment period. Adapalene 0.3% gel was safe and effective in the long-term (up to 1 year) treatment of subjects with acne vulgaris.