Novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris in a preadolescent population.

BackgroundAcne vulgaris (acne) is a common skin condition in children and adolescents. Efficacy of tretinoin is well documented in studies that included pediatric patients (12-18 years of age). With acne routinely presenting in younger patients, data are needed in this important group. Lotion formulations are commonly used across dermatology and are well liked by patients.ObjectiveTo evaluate the safety and efficacy of a novel once-daily tretinoin 0.05% lotion in preadolescent subjects (≤ 13 years) with moderate-to-severe acne.MethodsPost hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies in moderate-to-severe acne. Preadolescent subjects (N = 154) randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory/noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear/almost clear). Safety, adverse events (AEs), and cutaneous tolerability evaluated throughout.ResultsAt Week 12, mean percent reduction in inflammatory and noninflammatory lesion counts were 49.5% and 44.0% compared with 31.4% and 18.8% with vehicle (both P = 0.001). Treatment success was achieved by 23.7% of subjects by Week 12, compared with 7.2% (P = 0.009). The majority of AEs were mild and transient: most frequently were application site pain (5.6%) and application site dryness (2.8%). Local cutaneous safety and tolerability assessments were generally mild-to-moderate and improved by Week 12.ConclusionsTretinoin 0.05% lotion was significantly more effective than vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in preadolescent acne. It was well tolerated, with all treatment-related AEs deemed mild or moderate

Long-term safety and efficacy of trifarotene 50 μg/g cream, a first-in-class RAR-γ selective topical retinoid, in patients with moderate facial and truncal acne.

BackgroundTreatment for both facial and truncal acne has not sufficiently been studied.ObjectivesTo evaluate the long-term safety and efficacy of trifarotene in both facial and truncal acne.MethodsIn a multicentre, open-label, 52-week study, patients with moderate facial and truncal acne received trifarotene 50 μg/g cream (trifarotene). Assessments included local tolerability, safety, investigator and physician's global assessments (IGA, PGA) and quality of life (QOL). A validated QOL questionnaire was completed by the patient at Baseline, Week 12, 26 and 52/ET.ResultsOf 453 patients enrolled, 342 (75.5%) completed the study. Trifarotene-related treatment-emergent adverse events (TEAEs) were reported in 12.6% of patients, and none was serious. Most related TEAEs were cutaneous and occurred during the first 3 months. Signs and symptoms of local tolerability were mostly mild or moderate and severe signs, and symptoms were reported for 2.2% to 7.1% of patients for the face and 2.5% to 5.4% for the trunk. Local irritation increased during the first week of treatment on the face and up to Weeks 2 to 4 on the trunk with both decreasing thereafter. At Week 12, IGA and PGA success rates were 26.6% and 38.6%, respectively. Success rates increased to 65.1% and 66.9%, respectively at Week 52. Overall success (both IGA and PGA success in the same patient) was 57.9% at Week 52. At Week 52 visit, 92/171 (53.8%) patients who had completed their assessments had scores from 0 to 1 (i.e. no effect of acne on their QOL) vs. 47/208 (22.6%) patients at Baseline visit.ConclusionIn this 52-week study, trifarotene was safe, well tolerated and effective in moderate facial and truncal acne

Crisaborole Ointment Improves Quality of Life of Patients with Mild to Moderate Atopic Dermatitis and Their Families.

IntroductionThe impact of crisaborole ointment, a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD), on quality of life (QoL) was assessed in two identically designed phase 3 studies (AD-301: NCT02118766; AD-302: NCT02118792, both at http://www.clinicaltrials.gov ).MethodsIn both studies, patients aged ≥ 2 years with mild to moderate AD per the Investigator's Static Global Assessment were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. QoL was assessed using the Children's Dermatology Life Quality Index (CDLQI) (2-15 years), the Dermatology Life Quality Index (DLQI) (≥ 16 years), and the Dermatitis Family Impact Questionnaire (DFI) (parents/caregivers/family of patients aged 2-17 years). Established QoL score severity bands provided clinical context.ResultsGreater mean improvement in QoL was observed in crisaborole-treated patients than in vehicle-treated patients at day 29 [mean change from baseline (∆BL), CDLQI: - 4.6 vs. - 3.0; P < 0.001; DLQI: - 5.2 vs. - 3.5; P = 0.015]. At baseline, more than half the patients had a "moderate effect" or higher of AD on QoL. At day 29, there was a trend toward more crisaborole- than vehicle-treated patients having "small effect" to "no effect", The QoL of parents/caregivers/family improved more for crisaborole-treated than for vehicle-treated patients (∆BL, DFI: - 3.7 vs. - 2.7; P = 0.003).ConclusionCrisaborole treatment results in clinically meaningful improvement in QoL for patients and their parents/caregivers/families.Trial registrationAD-301: http://www.clinicaltrials.gov , NCT02118766; AD-302: http://www.clinicaltrials.gov , NCT02118792.FundingAnacor Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., New York, NY

275 Effects of ruxolitinib cream on sleep and quality of life over 52 weeks in black patients with atopic dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease with phenotypic differences across race and can affect sleep and quality of life (QoL). In 2 phase 3 studies of identical design (TRuE-AD1/TRuE-AD2), patients (pts; ≥12 y with AD for ≥2 y; Investigator’s Global Assessment score 2/3; 3%–20% affected body surface area) were randomized (2:2:1) to twice-daily 0.75% or 1.5% ruxolitinib (RUX; Janus kinase [JAK]1/JAK2 inhibitor) cream or vehicle for 8 wk (continuous treatment), followed by a long-term safety period (LTS; as-needed treatment) up to Wk 52. Pts randomized to RUX cream remained on their regimen during the LTS; pts on vehicle were rerandomized to either RUX cream strength. For Black pts who were initially randomized to the 0.75% RUX cream/1.5% RUX cream/vehicle to 0.75% RUX cream/vehicle to 1.5% RUX cream groups and continued in the LTS (n=91/97/25/22), sleep-related impairment and sleep disturbance scores per Patient-Reported Outcomes Measurement Information System at baseline (BL) were 16.3/16.4/15.0/17.5 and 18.9/19.7/17.9/19.8, respectively. Scores had decreased (less impairment) at LTS start in the RUX cream groups (Wk 8; 14.2/14.7/16.1/15.5 and 16.7/17.5/19.0/19.4) and were below BL at Wk 52 in all groups (14.3/14.8/13.9/14.4 and 18.0/18.0/17.4/16.3). Dermatology Life Quality Index (DLQI) scores were decreased at Wk 8 (mean change from BL, −7.4/−6.6/−3.8/−4.8); decreased scores were maintained to Wk 52 (−7.1/−6.5/−5.6/−8.8). Results were similar for children’s DLQI (Wk 8, −4.0/−6.9/−4.0/−3.0 [n=12/9/1/3]; Wk 52, −5.6/−11.6/−12.0/−7.3 [n=9/7/1/4]). In summary, sleep and QoL improved with RUX cream; improvements were maintained for 44 wk with as-needed use in Black pts

287 Effects of ruxolitinib cream on pruritus in black patients with atopic dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease that has phenotypic differences across race and can be more severe in Black patients. In two phase 3 identical design studies (TRuE-AD1/TRuE-AD2), patients (≥12 years old with AD for ≥2 years, Investigator’s Global Assessment [IGA] score 2/3, 3%–20% affected body surface area) were randomized (2:2:1) to twice-daily 0.75% or 1.5% ruxolitinib (Janus kinase [JAK]1/JAK 2 inhibitor) cream or vehicle for 8 weeks. Here we describe the effect of ruxolitinib cream on itch in Black patients using pooled data from the 2 studies (n=292). Mean itch numerical rating scale (NRS) score at baseline was 5.3/5.4 for ruxolitinib cream (0.75%/1.5%) and 5.7 for vehicle. Reductions in mean itch NRS score with ruxolitinib cream (0.75%/1.5%) were evident within approximately 12 hours of first application (–0.6/–0.7 vs −0.2 for vehicle), with statistically significant reductions by Day 4 vs vehicle (–1.4/–1.6 vs –0.6; both P\u3c0.05). For those with baseline itch NRS ≥4 (n=187; 64.0%), more patients achieved ≥4-point itch NRS improvement vs vehicle by Day 2 (6.1%/16.4% vs 0%); this increased to 15.9%/26.6% vs 3.0% on Day 7 and 30.1%/43.2% vs 17.5% at Week 8 (P=0.212/P=0.009). More patients applying 0.75%/1.5% ruxolitinib cream vs vehicle reported no days of itch per question 1 of the Patient-Oriented Eczema Measure (POEM) at Week 2 (19.0%/19.4% vs 5.3%); this increased at Week 8 (34.0%/30.8% vs 12.2%). In summary, ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black patients with AD

Coherent optical wavelength conversion via cavity-optomechanics

We theoretically propose and experimentally demonstrate coherent wavelength conversion of optical photons using photon-phonon translation in a cavity-optomechanical system. For an engineered silicon optomechanical crystal nanocavity supporting a 4 GHz localized phonon mode, optical signals in a 1.5 MHz bandwidth are coherently converted over a 11.2 THz frequency span between one cavity mode at wavelength 1460 nm and a second cavity mode at 1545 nm with a 93% internal (2% external) peak efficiency. The thermal and quantum limiting noise involved in the conversion process is also analyzed, and in terms of an equivalent photon number signal level are found to correspond to an internal noise level of only 6 and 4x10-3 quanta, respectively.Comment: 11 pages, 7 figures, appendi

International observational atopic dermatitis cohort to follow natural history and treatment course: TARGET-DERM AD study design and rationale

INTRODUCTION: As new topical and systemic treatments become available for atopic dermatitis (AD), there is a need to understand how treatments are being used in routine clinical practice, their comparative effectiveness and their long-term safety in diverse clinical settings. METHODS AND ANALYSIS: The TARGET-DERM AD cohort is a longitudinal, observational study of patients with AD of all ages, designed to provide practical information on long-term effectiveness and safety unobtainable in traditional registration trials. Patients with physician-diagnosed AD receiving prescription treatment (topical or systemic) will be enrolled at academic and community clinical centres. Up to 3 years of retrospective medical records, 5 years of prospective medical records, and optional biological samples and patient-reported outcomes will be collected. The primary aims include characterisation of AD treatment regimens, evaluation of response to therapy, and description of adverse events. ETHICS AND DISSEMINATION: TARGET-DERM has been approved by a central IRB (Copernicus Group IRB, 5000 Centregreen Way Suite 200, Cary, North Carolina 27513) as well as local and institutional IRBs. No additional Ethics Committee reviews. Results will be reviewed by a publications committee and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03661866, pre-results

Impact of climate change on atopic dermatitis: A review by the International Eczema Council

Atopic dermatitis (AD), the most burdensome skin condition worldwide, is influenced by climatic factors and air pollution; however, the impact of increasing climatic hazards on AD remains poorly characterized. Leveraging an existing framework for 10climatic hazards related to greenhouse gas emissions, we identified 18 studies with evidence for an impact on AD through a systematic search. Most climatic hazards had evidence for aggravation of AD the impact ranged from direct effects like particulate matter-induced AD exacerbations from wildfires to the potential for indirect effects like drought-induced food insecurity and migration. We then created maps compar-ing the past, present, and future projected burden of climatic hazards to global AD prevalence data. Data are lacking, especially from those regions most likely to experience more climatic hazards. We highlight gaps important for future research: under-standing the synergistic impacts of climatic hazards on AD, long-term disease activity, the differential impact on vulnerable populations, and how basic mechanisms explain population-level trend

Generalized nonreciprocity in an optomechanical circuit via synthetic magnetism and reservoir engineering

Synthetic magnetism has been used to control charge neutral excitations for applications ranging from classical beam steering to quantum simulation. In optomechanics, radiation-pressure-induced parametric coupling between optical (photon) and mechanical (phonon) excitations may be used to break time-reversal symmetry, providing the prerequisite for synthetic magnetism. Here we design and fabricate a silicon optomechanical circuit with both optical and mechanical connectivity between two optomechanical cavities. Driving the two cavities with phase-correlated laser light results in a synthetic magnetic flux, which in combination with dissipative coupling to the mechanical bath, leads to nonreciprocal transport of photons with 35dB of isolation. Additionally, optical pumping with blue-detuned light manifests as a particle non-conserving interaction between photons and phonons, resulting in directional optical amplification of 12dB in the isolator through direction. These results indicate the feasibility of utilizing optomechanical circuits to create a more general class of nonreciprocal optical devices, and further, to enable novel topological phases for both light and sound on a microchip.Comment: 18 pages, 8 figures, 4 appendice