Linda F. Stein Gold MD,a Lynda Spelman MBBS FACD,b Mary C. Spellman MD,c Matilda H. Hughes CCRA,d and Lee T. Zane MDd
BACKGROUND: Crisaborole is a novel, boron-based, small-molecule, topical phosphodiesterase-4 inhibitor in development for the treatment
of patients with mild to moderate atopic dermatitis (AD).
METHODS: In this multicenter, randomized, double-blind, dose-ranging, phase 2 study, adolescent patients 12 to 17 years of age with mild to moderate AD and 2 distinct target AD lesions were randomized to once-daily (QD) or twice-daily (BID) treatment with crisaborole
topical ointment. For each patient, 2 target lesions were randomized to receive 29 days of treatment with 0.5% or 2% crisaborole topical ointment. The primary endpoint was change from baseline in AD severity index (ADSI) score for each lesion. Exploratory efficacy endpoints and safety were also assessed.
RESULTS: A total of 86 patients were enrolled and received crisaborole topical ointment 0.5% or 2% QD (n=44) or BID (n=42). All dosing regimens produced dose-related improvements in ADSI as well as in all 5 component signs and symptoms of AD (erythema, excoriation,
exudation, lichenification, and pruritus). The greatest improvements were consistently observed with crisaborole topical ointment, 2% applied BID. With this regimen, ADSI improved from baseline by 71%, and total or partial clearance of target lesions (ADSI ≤2) was achieved by 62% of patients after 29 days of treatment. Both doses of crisaborole topical ointment were well tolerated; mild application site reactions were the only treatment-related adverse events (QD, n=3; BID, n=1).
CONCLUSION: These results provide preliminary evidence of the efficacy and safety of crisaborole topical ointment, 2% applied topically BID in adolescents with mild to moderate AD.
J Drugs Dermatol. 2015;14(12):1394-1399.
Richard Martin MSc,a Jessica B. Henley PhD,b Patrick Sarrazin MD,c and Sophie Seité PhDd
BACKGROUND: Changes in the composition of microbial communities that colonize skin have been linked to several diseases including psoriasis. Nevertheless, the intra-individual dynamics and how these communities respond to balneotherapy remain poorly understood.
METHODS: This open label study was conducted between July and September 2012. Microbial communities of patients with psoriasis vulgaris were characterized prior and post a 3-week selenium-rich water balneotherapy treatment at the thermal care center La Roche-Posay (La Roche-Posay, France). Balneotherapy consisted of high-pressure filiform showers, baths, facial, and body spray treatments as well as La Roche-Posay thermal spring water (LRP-TSW) consumption. Swabs were taken from affected and proximal unaffected skin and the 16S rRNA bacterial gene was used to analyze the composition of bacterial communities. Using the same 16S rRNA gene tool, we tried to describe the LRP-TSW bacterial landscape.
RESULTS: This study included 54 patients diagnosed with moderate to severe forms of psoriasis vulgaris. After eliminating individuals lacking paired samples from both visits, 29 individuals were analyzed for their microbiome profile. Shannon Diversity Index and global bacterial landscape indicate similar microbial communities on both unaffected and adjacent affected skin. PASI values decreased post-balneotherapy implying improvement of disease severity. No significant change in the Shannon Diversity Index was noticed at the end of the third week. The average taxonomic composition of skin microbial communities associated with unaffected and affected skin of psoriatic patients post-balneotherapy shows that treatment with LRP-TSW significantly increased the level of Xanthomonas genus and, to a lesser extent, Corynebacterium genus. The Xanthomonas genus belongs to the main Xanthomonadaceae family found in LRP-TSW and also on healthy skin.
CONCLUSIONS: In psoriatic patients, a poor bacterial biodiversity was noticed and the bacterial communities were similar on unaffected and affected adjacent skin. Family analysis identified, for the first time, Xanthomonadaceae belonging to Proteobacteria phylum and known to be keratolytic, associated with the clinical improvement observed after a 3-week balneotherapy treatment. This data supports the interest of selenium-rich thermal spring water in the treatment of psoriasis vulgaris.
J Drugs Dermatol. 2015;14(12):1400-1405.
Hema Sundaram MD,a Michael Gold MD,b Heidi Waldorf MD,c Mary Lupo MD,d Vivien L. Nguyen PharmD,e and Jwala Karnik MDe
BACKGROUND: This multicenter, open-label pilot study evaluated safety, efficacy and tolerability of a topical formulation containing a multipotent growth factor resignaling complex (MRCx), when applied to infraorbital and lateral canthal skin.
METHODS: Thirty-nine female subjects with mean age of 56.8 years who had periorbital lines and wrinkles, uneven skin texture, puffiness,
and lack of skin firmness were enrolled, and 38 completed the study. All subjects applied the multipotent growth factor formulation
bilaterally to the periorbital area, twice daily for 60 days. Efficacy and treatment-related adverse events were evaluated at Baseline and days 14, 30, and 60. Investigators rated the periorbital areas based on 10-point scales.
RESULTS: Subjects’ self-reported compliance with treatment was greater than 99% throughout the study. At day 60, all subjects had improvement in infraorbital brightness (≥ 2 points), moistness (≥ 2 points), wrinkles (≥ 1 point), sallowness (≥ 1 point), crepiness (≥ 1 point), smooth texture (≥ 1 point), skin tightness (≥ 1 point), and skin tone (≥ 1 point). Investigator-rated assessments showed ≥ 1-point improvement for lateral canthal wrinkles, dyschromia/mottled pigmentation, skin tone, overall brightness, and moistness. Investigator-rated scoring on the Global Aesthetic Improvement Scale (GAIS) demonstrated that 67.6% of subjects were much improved/improved at day 14, and 63.1% remained improved at day 60. Overall, 76.2% and 79.0% of subjects were very pleased/pleased/mostly pleased with the appearance of their infraorbital and lateral canthal areas at day 60. Adverse events comprised one case of mild canthal erythema,
and one case of mild eye irritation, both of which were respectively resolved.
CONCLUSIONS: This pilot study demonstrated that the topical multipotent growth factor formulation was safe, effective and well tolerated for periorbital skin rejuvenation.
J Drugs Dermatol. 2015;14(12):1410-1417.
BACKGROUND: Over-the-counter acne treatments have assumed more importance for the dermatologist as access and affordability of prescription acne medications has decreased.
AIM: This research evaluated the efficacy of a three step acne treatment regimen containing stabilized botanical anti-inflammatory ingredients as compared to a currently marketed acne regimen.
METHOD: 80 female/male subjects 12+ years with mild to moderate acne (at least 10 inflammatory and 10 non-inflammatory lesions) were enrolled for 12 weeks and randomized to use the study botanical anti-inflammatory acne regimen or the traditional benzoyl peroxide
comparator. Evaluations included investigator global assessment, investigator tolerability assessment, acne lesion characteristics (erythema, lesion height, diameter of inflammation, and amount of pus), subject product assessment, and digital photos at baseline, 2, 4, and 12 weeks.
RESULTS: The botanical regimen outperformed the comparator in terms of target lesion erythema, height, inflammation, and pus at weeks 2 and 4, perhaps due to anti-inflammatory ingredients, however parity was reached between the two products by week 12. No difference in lesion counts between the two groups was noted at week 2, however by week 4, there was a lower lesion count with the study regimen in terms of closed comedones (P<0.001) and inflammatory (P=0.016) lesions than the comparator. This statistically significant difference continued into week 12 with a reduction in closed comedones (P=0.006) for the study regimen.
CONCLUSION: Modern OTC cosmetic formulation ingredients including emollients, anti-inflammatory/antioxidants, and sensitive skin modulators provided an improved skin appearance, less lesional erythema, and a better overall appearance in subjects with acne treated for 12 weeks.
J Drugs Dermatol. 2015;14(12):1418-1421.
David McDaniel MDa and Petra Samková MDb
BACKGROUND AND OBJECTIVE: When evaluating self-image, research confirms that the main focus of dissatisfaction for the majority of women is the size and shape of their bodies, particularly their hips, waist and thighs. The appearance of a woman’s thighs is often distanced from what she views as her ideal shape and size and is largely out of her control due to gender specific fat deposition. The issue of excessive subcutaneous fat deposits in the lateral thigh area is enhanced by the resistivity of local adipocytes to lipolysis. Subjects in this study underwent treatment of the bilateral inner and outer thighs using a non-contact field radiofrequency device (BTL Vanquish Flex Applicator, BTL Industries Inc., Boston, MA). The main objective of this study is to evaluate the safety and efficacy of the device for reducing the circumference of the inner and outer thighs as well as improving the overall contour of the treatment area.
MATERIALS AND METHODS: A total of 30 female subjects age 32 to 59 (average 42.4) were enrolled in the study. After meeting the inclusion/
exclusion criteria each subject received 4 weekly 30-minute bilateral thigh treatments (1 hour total treatment time). As the primary outcomes, circumferential reduction was measured and clinical before and after photographs were taken for assessment. Safety of the device was assessed by means of reported adverse events.
RESULTS: All 30 subjects completed the entire treatment series and 1 month follow-up visit. The average reduction measured on both thighs was 3.86 cm with statistical significance P< 0.05. There was no significant change in weight for any of the subjects. During the course of the study two adverse events occurred, but were deemed unrelated to the treatment.
CONCLUSIONS: Based on the measurements obtained the device under investigation was considered safe and effective in terms of improved contour and circumferential reduction of inner and outer thighs.
J Drugs Dermatol. 2015;14(12):1422-1424.
Jonathan Weiss MD,a Linda Stein Gold MD,b Matthew Leoni MD,c Maria Jose Rueda MD,d Hong Liu Msc,c and Emil Tanghetti MDe
BACKGROUND: More effective therapies are needed in the specific treatment of severe inflammatory acne vulgaris.
OBJECTIVES: To demonstrate superior efficacy of adapalene 0.3%-benzoyl peroxide 2.5% gel (0.3% A/BPO) vs. vehicle, and to assess efficacy of 0.3% A/BPO vs. 0.1% A/BPO in subjects with severe inflammatory acne (Investigator’s Global Assessment [IGA] of 4) in the context of a larger trial in a moderate and severe population.
METHODS: This was a multicenter, randomized, double-blind, parallel-group, 12-week study. Subjects were randomized to receive 0.3% A/BPO, 0.1% A/BPO (benchmark) or vehicle (comparator) once daily for 12 weeks. Co-primary efficacy endpoints were success rate at week 12 (percentage of subjects rated “clear” or “almost clear,” ≥3-grade IGA improvement), and change in inflammatory (IN) and noninflammatory (NIN) lesion counts from baseline to week 12. Secondary efficacy endpoints were percent changes in IN and NIN lesion
counts. Safety endpoints were incidence of adverse events (AEs) and local tolerability signs/symptoms.
RESULTS: In the severe inflammatory acne population, a total of 252 subjects were randomized with 106, 112 and 34 subjects in the 0.3% A/BPO, 0.1% A/BPO and vehicle groups, respectively, reaching a high rate of study completion (88.5%). At week 12, both 0.3% A/BPO and 0.1% A/BPO were superior to vehicle in terms of lesion count reduction. However for success rate, only 0.3% A/BPO achieved significantly greater efficacy over vehicle with a treatment difference of 20.1% (31.9% vs. 11.8%; 95% Confidence Interval (CI): [6.0%, 34.2%], P=.029), whereas 0.1% A/BPO did not (treatment difference vs. vehicle of 8.8%; P=.443). This translates to an 11% difference between active treatments in favor of 0.3% A/BPO. Also, 0.3% A/BPO was safe and well tolerated.
CONCLUSIONS: Availability of this new treatment option should allow clinicians to better customize severe inflammatory acne management,
and the high-strength product provides a step-up treatment when needed.
J Drugs Dermatol. 2015;14(12):1427-1435.
E. Victor Ross MDa and James Childs PhDb
BACKGROUND AND OBJECTIVE: Wavelength, fluence and pulse width are primary device parameters for the treatment of skin and hair conditions. Wavelength selection is based on tissue scatter and target chromophores. Pulse width is chosen to optimize target heating. Energy absorbed by a target is determined by fluence and spot size of the light source as well as the depth of the target. We conducted an in vitro skin study and simulations to compare heating of a target at a particular depth versus spot size.
STUDY DESIGN/MATERIALS AND METHODS: Porcine skin and fat tissue were prepared and separated to form a 2mm skin layer above a 1 cm thick fat layer. A 50μm thermocouple was placed between the layers and centered beneath a 23 x 38 mm treatment window of an 805 nm diode laser device (Vectus, Cynosure, Westford, MA). Apertures provided various incident beam spot sizes and the temperature rise of the thermocouple was measured for a fixed fluence.
RESULTS: The 2mm deep target's temperature rise versus treatment area showed two regimes with different positive slopes. The first regime up to approximately 1 cm2 area has a greater temperature rise versus area than that for the regime greater than 1 cm2. The slope in the second regime is nonetheless appreciable and provides a fluence reduction factor for skin safety. The same temperature rise in a target at 2 mm depth (typical hair bulb depth in some areas) is realized by increasing the area from 1 to 4 cm2 while reducing the fluence by half.
CONCLUSIONS: The role of spot size and in situ beam divergence is an important consideration to determine optimum fluence settings that increase skin safety when treating deeper targets.
J Drugs Dermatol. 2015;14(12):1437-1442.
Hervé Raspaldo MD,a Jonquille Chantrey MD,b Lakhdar Belhaouari MD,c David Eccleston MD,d Roy Saleh MD,e Raj Acquilla MD,f and Diane K. Murphy MBAg
BACKGROUND: Juvéderm® Volbella® with Lidocaine is a hyaluronic acid filler suited for lip enhancement.
OBJECTIVE: Evaluate the safety and effectiveness of Juvéderm Volbella with Lidocaine versus non-animal stabilized hyaluronic acid with lidocaine (Restylane-L®).
METHODS: This study randomized 280 subjects desiring lip enhancement to Juvéderm Volbella with Lidocaine or Restylane-L. Investigators
rated outcomes using Allergan’s Lip Fullness Scale (LFS), Perioral Lines Severity Scale, and Oral Commissures Severity Scale. Independent
central reviewers (ICRs) assessed 3-dimensional photographs using these scales. Noninferiority of Juvéderm Volbella with Lidocaine to Restylane-L was based on ICR assessment of LFS responders (≥1-point improvement from baseline) at month 3. Subjects were evaluated up to 12 months and after repeat treatment.
RESULTS: Juvéderm Volbella with Lidocaine was noninferior to Restylane-L at 3 months. Investigator assessments showed significant improvements in lip fullness (P≤.03), perioral lines (P≤.04), and oral commissures (P≤.03) with Juvéderm Volbella with Lidocaine versus Restylane-L at months 6 to 12. There was less acute swelling and fewer severe injection site responses with Juvéderm Volbella with Lidocaine. Safety and effectiveness of repeat treatment with Juvéderm Volbella with Lidocaine was comparable to initial treatment, regardless of initial filler.
CONCLUSIONS: Juvéderm Volbella with Lidocaine is safe and effective for lip and perioral enhancement, with effectiveness lasting up to 12 months.
J Drugs Dermatol. 2015;14(12):1444-1452.
Jay Birnbaum PhD,a Anne Le Moigne,b Lisa Dispensa MS RD,c and Larry Buchner BAd
Although the FDA does not require documentation of efficacy of dietary supplements, prospective clinical studies, including randomized
controlled trials, have been conducted with individual micronutrients alone and in combination with other ingredients for promoting skin health. Proposed mechanisms include antioxidation, anti-inflammation, photoprotection, collagen formation, reductions in matrix metalloproteinases, and other effects on photoaging. Literature searches were conducted to identify clinical trials assessing multicomponent
dietary supplement formulations on photoaging outcomes. Sixteen studies of various nutrient and non-nutrient ingredients, including essential micronutrients (vitamins, minerals), plant extracts (polyphenols, carotenoids), and marine- or animal-derived ingredients,
were identified. Studies were single center, 2–12 months in duration, primarily enrolled women, and evaluated numerous outcomes,
including investigator/subject assessments and instrumental/objective measures. Methods to control for potential confounders were implemented in some studies, including limiting sun exposure, cosmetic procedures, and changes in dietary habits/body weight. Given the range of different products, clinical/methodologic heterogeneity, insufficient detail in reporting, and lack of comparable outcome
measures, quantitative analysis of results was not possible. Results of individual studies revealed significant improvements from baseline for the dietary supplement group(s) on ≥1 endpoint across all studies; significant differences from placebo were observed in 7 of 12 controlled studies (although only 1 study designated a prospectively defined primary endpoint). Most products had only been tested in 1 study; confirmatory studies were rarely conducted per the publicly available literature. Meaningful assessment of dietary supplements, which typically contain nutrients found in the diet, requires unique methodologic considerations and endpoints appropriate
for measuring changes that are more subtle and gradual than those observed with topical/injectable products. Although definitive conclusions could not be drawn from the existing evidence, available data are supportive of beneficial effects of oral multicomponent supplements on skin health. Confirmation of positive effects with the same formulation/endpoint from more than a single study/investigator
J Drugs Dermatol. 2015;14(12):1453-1461.
Braden McKnight BS,a Rachel Tobin BS,b Yasmeen Kabir MD,c and Ronald Moy MDa
BACKGROUND: Non-ablative treatments for excess subcutaneous fat have been increasingly integrated into dermatologic practice.
Objective: The objective of this study was to determine the safety and efficacy of a tripolar radiofrequency device on tightening skin and reducing the circumference of the upper arms.
METHODS & MATERIALS: Twelve females received eight weekly non-ablative treatments using a tripolar radiofrequency device on the anterior and posterior upper arms. Evaluations included body weight, photographs, and circumference measurements at baseline and each subsequent week throughout the 8-week time period. The subjects and the investigator completed evaluations of clinical improvement
using a 5-point assessment scale.
RESULTS: A significant circumference reduction was achieved in each arm of all twelve patients. A mean reduction of 1.99 ± 0.94 cm (P=0.001) was observed between the initial and final measurements after the 8-week treatment period. At the 4-week follow up, the average circumferential reductions of the posterior and anterior upper arms were sustained. Patient evaluations indicated moderate to good improvement of size, tightness, and overall appearance. The procedure was well tolerated without pain.
CONCLUSION: Tripolar radiofrequency devices offer a safe and effective non-invasive technology with beneficial effects on the circumferential
reduction and overall appearance of the posterior and anterior upper arms.
J Drugs Dermatol. 2015;14(12):1463-1466.
Craig Leonardi MD,a Jerry Bagel MD,b Paul Yamauchi MD,c David Pariser MD,d Zhenyi Xu MD,e Martin Olesen MD,e* Marie Louise østerdal MSc,e and Linda Stein Gold MDf
INTRODUCTION: An innovative aerosol foam formulation of calcipotriene 0.005% (Cal) plus betamethasone dipropionate 0.064% (BD) designed to improve treatment outcomes.
OBJECTIVE: To compare the efficacy and safety of Cal/BD aerosol foam with aerosol foam vehicle in patients with psoriasis.
DESIGN: Phase III, double-blind, randomized PSO-FAST (Cal/BD foam in PSOriasis vulgaris, a Four-week, vehicle-controlled, efficacy And Safety Trial) study recruited patients with ≥ mild severity psoriasis of the trunk and/or limbs from 27 US outpatient sites (NCT01866163). Patients were randomized (3:1) to Cal/BD foam or vehicle once-daily for 4 weeks. Primary outcome: proportion of patients at week 4 who achieved treatment success according to physician’s global assessment. Secondary outcomes: modified (excluding head) psoriasis
area and severity index (mPASI) and patient's assessment of itch (visual analog scale). Safety was monitored by adverse events/calcium homeostasis.
RESULTS: 426 patients enrolled between June and October 2013 (Cal/BD foam, n=323; vehicle, n=103). At week 4, significantly more patients using Cal/BD foam achieved treatment success versus vehicle (53.3 versus 4.8%; OR 30.3, 95% CI 9.7,94.3; P < .001) and mean mPASI score was significantly lower for patients using Cal/BD foam than vehicle (2.0 versus 5.5; adjusted difference –3.3, P <.001). Significantly greater itch relief was observed for patients using Cal/BD foam than vehicle (P = .010 at day 3, P < .001 from day 5). Adverse drug reactions were reported in 10 Cal/BD foam patients (3.1%) and two vehicle patients (1.9%); events occurred in one patient each except application site pain (Cal/BD foam, two patients; vehicle, one patient). There were no clinically significant changes in calcium homeostasis.
CONCLUSIONS: Cal/BD foam was efficacious, achieved rapid itch relief and was well tolerated in patients with body psoriasis. This innovative
aerosol foam formulation is expected to become a valuable treatment option.
J Drugs Dermatol. 2015;14(12):1468-1477.