Publications

2008

Frangos JE, Kimball AB. Clobetasol propionate emollient formulation foam in the treatment of corticosteroid-responsive dermatoses.. Expert opinion on pharmacotherapy. 2008;9(11):2001-7. doi:10.1517/14656566.9.11.2001

BACKGROUND: Topical corticosteroids are the most common treatment modality for patients with psoriasis and atopic dermatitis; however, the efficacy of topical corticosteroids is often hampered by barriers to patient adherence, such as lack of efficacy, side effects and inconvenience. Recently published studies have investigated the safety and efficacy of a novel emollient foam (EF) formulation of clobetasol propionate (CP), a class I topical corticosteroid in psoriasis and atopic dermatitis.

OBJECTIVES: To summarize recent literature on CP EF foam, and to evaluate recent Phase II and III clinical trials of CP EF foam in psoriasis and atopic dermatitis.

METHODS: The MEDLINE (1950 - January 2008) database was searched using the following terms: 'clobetasol propionate foam', 'topical corticosteroids', 'topical glucocorticoids', 'psoriasis' and 'atopic dermatitis'. Results were evaluated for relevance and quality, and additional references were obtained from bibliographies of selected articles.

CONCLUSION: CP EF foam appears to be safe and effective for corticosteroid-responsive dermatoses in adults and children > or = 12 years of age. As compared to its hydroethanolic foam predecessor, CP EF presents a potential advance for patients who are less likely to tolerate alcohol-based foam. As alcohol-based foams can be irritating and cause stinging in non-hair-bearing areas, this new emollient formulation has the potential to widen the use of CP foam to more patients with atopic dermatitis and to more non-scalp body sites in patients with psoriasis.

Freeman SR, Greene RE, Kimball AB, et al. US dermatology residents’ satisfaction with training and mentoring: survey results from the 2005 and 2006 Las Vegas Dermatology Seminars.. Archives of dermatology. 2008;144(7):896-900. doi:10.1001/archderm.144.7.896

OBJECTIVE: To evaluate residents' satisfaction with dermatology training and mentorship.

DESIGN: Written survey.

SETTING: The Las Vegas Dermatology Seminar in 2005 and 2006.

PARTICIPANTS: Graduating dermatology residents in the United States.

MAIN OUTCOME MEASURES: Satisfaction with and importance of 26 training components, overall training satisfaction, satisfaction with availability and quality of mentors, and time spent outside the clinics and classroom with mentors.

RESULTS: Of dermatology residents attending the 2005 and 2006 seminars, 57 (50%) and 49 (54%), respectively, completed the survey. In 2006, 38 more surveys were received by mail, for a combined total of 144 respondents. In 2005 and 2006, respectively, 44 (77%) and 66 (76%) residents scored training at or above 7 on a 10-point rating scale. Residents were most satisfied with peer teaching, medical dermatology training, pathology slide sessions, and live patient conferences and least satisfied with business management and dermoscopy training. Discrepancies between perceived importance and satisfaction were greatest for business management, time for independent study, and responsiveness to resident input. Residents spending 30 minutes (the median) or more per month outside of clinics and the classroom with someone they defined as a mentor reported higher training satisfaction (8.0 vs 7.2; P = .02). Resident-perceived program mentor availability (P = .001 in 2005, P=.002 in 2006) and quality (P =.002 in 2005, P < or = .001 in 2006) were also associated with increased overall training satisfaction.

CONCLUSIONS: Of 26 training components, residents were most dissatisfied with business management training. Resident training satisfaction was associated with program mentor availability and quality, as well as time spent with mentors.

Kimball AB, Gold MH, Zib B, Davis MW, Group CPEFFPCS III. Clobetasol propionate emulsion formulation foam 0.05%: review of phase II open-label and phase III randomized controlled trials in steroid-responsive dermatoses in adults and adolescents.. Journal of the American Academy of Dermatology. 2008;59(3):448-54, 454.e1. doi:10.1016/j.jaad.2008.04.020

BACKGROUND: Clobetasol propionate 0.05% emulsion foam was recently developed for use on multiple body sites.

OBJECTIVE: We sought to evaluate safety and efficacy of clobetasol emulsion foam 0.05% to treat steroid-responsive dermatoses in multiple age groups.

METHODS: A phase II open-label study evaluated the effect of clobetasol foam on the hypothalamic-pituitary-adrenal axis in 52 participants aged 6 years or older with mild-to-severe atopic dermatitis (AD). Cosyntropin stimulation test was used to determine the effect of clobetasol foam on hypothalamic-pituitary-adrenal axis, with a normal response considered to be a postinjection serum cortisol level greater than 18 mug/dL. Another phase II open-label pharmacokinetic safety study was conducted in 32 participants aged 12 years or older with mild-to-moderate plaque-type psoriasis. Pharmacokinetic parameters evaluated included maximal plasma concentration of clobetasol propionate, time to achieve maximum concentration, and area under the curve. Two phase III, randomized controlled studies assessed treatment success in participants aged 12 years or older with moderate-to-severe AD (N = 377) or mild-to-moderate plaque-type psoriasis (N = 497). In all studies, participants received study drug for 2 weeks. In the AD study, treatment success was determined using a composite end point requiring an Investigator's Static Global Assessment (ISGA) score of 0 or 1, erythema score of 0 or 1, induration/papulation score of 0 or 1, and improvement in the ISGA score of at least two grades from baseline. Likewise, the study in plaque-type psoriasis used a composite end point requiring an ISGA score of 0 or 1, erythema score of 0 or 1, scaling score of 0 or 1, plaque thickness score of 0, and improvement in the ISGA score of at least two grades from baseline.

RESULTS: Significantly more participants achieved treatment success on clobetasol foam than vehicle foam (P < .0001 and P = .0005 for each study). Reversible hypothalamic-pituitary-adrenal axis suppression was observed in 27% of participants aged 18 years or older and 47% in participants aged between 6 and younger than 12 years, but 0% in participants aged between 12 and younger than 18 years.

LIMITATIONS: The studies evaluated short-term use only.

CONCLUSION: Clobetasol emulsion formulation foam is safe and effective for treatment of moderate-to-severe AD and mild-to-moderate plaque-type psoriasis in patients aged 12 years or older.

Kimball AB. Advances in the treatment of acne.. The Journal of reproductive medicine. 2008;53(9 Suppl):742-52.

Acne vulgaris affects most people at some time in their life. This common condition can have devastating effects on a person's quality of life and may leave permanent scars. Treatment options, which are designed to disrupt one or more of the pathogenic features that characterize acne, include topical therapies (e.g., antibiotics, retinoids, benzoyl peroxide and combination products), systemic treatments (e.g., oral antibiotics, hormonal therapies and oral retinoids, which are indicated for severe recalcitrant nodulocystic acne), and, to a lesser extent, light-based and physical treatments. Combination oral contraceptives (COCs) represent one type of hormonal treatment. Their mode of action is to reduce the availability of free testosterone, which stimulates the sebaceous glands to produce sebum. Most COCs used in the United States contain progestins derived from 19-nortestosterone, giving them at least some degree of androgenic activity. Of the 3 COCs with an FDA indication for the treatment of moderate acne, only YAZ contains drospirenone, a progestin that combines no androgenic activity with antiandrogenic activity. This drospirenone-containing COC has been shown to be effective in reducing both inflammatory and noninflammatory acne lesions.

Kimball AB, Kupper TS. Future perspectives/quo vadis psoriasis treatment? Immunology, pharmacogenomics, and epidemiology.. Clinics in dermatology. 2008;26(5):554-61. doi:10.1016/j.clindermatol.2007.11.007

Advances in the understanding and treatment of psoriasis in the past several years have been remarkable. New frontiers include better understanding the immunologic pathways that underlie the disease and the development of personalized strategies to maximize the benefit and minimize the risk for patients. Although a cure may not be imminent, there are some strategies under examination that may lead us closer to this goal.

Kimball AB, Resneck JS. The US dermatology workforce: a specialty remains in shortage.. Journal of the American Academy of Dermatology. 2008;59(5):741-5. doi:10.1016/j.jaad.2008.06.037

INTRODUCTION: Since 1999, multiple surveys have documented a stable undersupply of dermatologic services in the United States. Factors contributing to the imbalance include changes in the demographics of the physician workforce, increased demand for services, and a limited number of training positions for new physicians. In response to the demand, there has also been a substantial influx of nonphysician clinicians into dermatology offices.

METHODS: We sought to follow up the large data set collected by the American Academy of Dermatology in 2002; the survey was repeated in 2005 and 2007. Response rates ranged from 30% to 35% and included more than 1200 respondents each year.

RESULTS: Few changes were noted in the metrics used to assess the balance of supply and demand in the US dermatology workforce between 2002 and 2007. Mean wait times for new patient appointments decreased slightly from 36 to 33 days. One third of practices continue to seek additional dermatologists. In 2007, 23% of practices reported employing a physician assistant and 10% a nurse practitioner (up from 15% and 8% in 2002). In 2007, typical dermatologists continued to spend the bulk of their direct patient care time in medical dermatology (23.9 hours, 63%), followed by surgery (10.2 hours, 27%), and then cosmetic dermatology (3.8 hours, 10%). A substantial subset of dermatologists (29%) spent half or more of their time in surgical and cosmetic dermatology combined. Although female dermatologists worked fewer total hours, they spent equal time caring for patients with medical dermatologic conditions, less time in surgical dermatology, and more time in cosmetic dermatology.

LIMITATIONS: The survey is potentially subject to inaccurate self-report and response bias. Although the results shed light on patient access and the dermatology workforce, they do not establish or quantify any impact on patients' health.

CONCLUSIONS: Between 2002 and 2007, despite continued increases in the number of nonphysician clinicians in US dermatology offices, there were only small changes in the overall metrics commonly used to assess workforce balance. These findings suggest persistent unmet demand, but, given divergent trends of ongoing increases in surgical and cosmetic dermatology, growth in the use of physician assistants and nurse practitioners, and an aging and expanding US population, the future balance of supply and demand remains difficult to predict. Nevertheless, careful workforce planning and deliberative consideration of the risks and benefits of rapidly emerging changes in the delivery of dermatologic care are essential to ensure access to high-quality care for patients with skin disease.

2007

OBJECTIVE: The effect of adalimumab on patient-reported outcomes (PROs) was evaluated in patients with moderate to severe psoriasis during the initial 16-week, double-blind period of a 52-week, Phase III, multicenter trial.

METHODS: Patients were randomized to placebo or adalimumab 80 mg at Week 0 and 40 mg every other week from Week 1 to Week 15. PROs were evaluated throughout the study and included the Dermatology Life Quality Index (DLQI), the Short Form 36 Health Survey (SF-36), the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAI-SHP), and several patient-rated symptom scales.

RESULTS: The adalimumab-treated group reported significantly greater improvements in DLQI total score (p<0.001), SF-36 Physical Component Summary score (p<0.001), and Mental Component Summary score (p<0.001) compared with the placebo-treated group over 16 weeks. Significant differences, favoring adalimumab, were also seen for the DLQI subscale scores (p < 0.001); SF-36 scale scores (p<0.001); WPAI-SHP work impairment (p<0.001), activity limitation (p<0.001), and overall work impairment scores (p<0.001); patient's global assessment of disease severity (p<0.001), psoriasis pain (p<0.001), and psoriasis-related pruritus (p = 0.002).

CONCLUSION: Adalimumab was efficacious in improving dermatology-specific and general health-related quality of life, work and activity limitations, and psoriasis-related symptoms in patients with moderate to severe psoriasis over a 16-week period.

Short RW, Chan JL, Choi JM, Egbert BM, Rehmus WE, Kimball AB. Effects of moisturization on epidermal homeostasis and differentiation.. Clinical and experimental dermatology. 2007;32(1):88-90.

Moisturizers are commonly used for routine skin care. This study assessed the effects of a moisturizer on barrier function, epidermal architecture, keratinocyte proliferation, and physiological regulation of the epidermis in photoaged but otherwise normal skin. Fifteen women with moderately photoaged forearms were treated twice a day for 4 weeks with a moisturizer containing dimethicone and glycerine. Baseline and post-treatment transepidermal water loss (TEWL) and ipsilateral forearm biopsies were obtained. Epidermal thickness, melanin levels, keratinocyte proliferation, and expression of keratins were evaluated. Induction of keratins 6 and 16, commonly associated with keratinocyte proliferation and wound healing, was observed. Epidermal thickness increased by 0.019 mm (P = 0.005), barrier function improved (TEWL decreased by 13%) and melanin intensity decreased (P = 0.004). Even nonxerotic, photoaged skin may appear younger, benefiting structurally and functionally from routine use of moisturizers containing dimethicone and glycerine.