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 10 climatic 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 comparing 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: understanding 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 trends.

Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.

BACKGROUND: For people with atopic dermatitis (AD) refractory to topical therapies, treatment with phototherapy and systemic therapies can be considered. Multiple biologic therapies and Janus kinase (JAK)inhibitors have been approved since 2014 to treat AD. These guidelines update the 2014 recommendations for management of AD with phototherapy and systemic therapies. OBJECTIVE: To provide evidence-based recommendations on the use of phototherapy and systemic therapies for AD in adults. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic agents, including biologics, oral JAK inhibitors, and other immunomodulatory medications. LIMITATIONS: Most randomized controlled trials of phototherapy and systemic therapies for AD are of short duration with subsequent extension studies, limiting comparative long-term efficacy and safety conclusions. CONCLUSIONS: We make strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. We make conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.

Executive summary: Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.

BACKGROUND: The summarized guidelines update the 2014 recommendations for the management of AD with phototherapy and systemic therapies. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of the evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic therapies, including biologics, oral Janus Kinase inhibitors, and other immunomodulatory medications. CONCLUSIONS: The evidence supported strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib and conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.

Tapinarof cream 1% once daily: Significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials.

BACKGROUND: Tapinarof cream 1% once daily (QD), a topical aryl hydrocarbon receptor agonist, downregulates pro-inflammatory Th2 cytokines, upregulates skin-barrier components, and reduces oxidative stress. OBJECTIVE: To assess tapinarof efficacy and safety in adults and children down to 2 years of age with atopic dermatitis (AD). METHODS: Eight hundred and thirteen patients were randomized to tapinarof or vehicle QD in two 8-week phase 3 trials. RESULTS: The primary efficacy endpoint, Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and ≥2-grade improvement from baseline at Week 8, was met with statistical significance in both trials: 45.4% versus 13.9% and 46.4% versus 18.0% (tapinarof vs vehicle; both P < .0001). Significantly superior Eczema Area and Severity Index 75 (EASI75) responses were also observed with tapinarof versus vehicle at Week 8: 55.8% versus 22.9% and 59.1% versus 21.2% (both P < .0001). Rapid improvements in patient-reported pruritus were also significant with tapinarof versus vehicle. Common adverse events (≥5%) of folliculitis, headache, and nasopharyngitis were mostly mild or moderate, with lower discontinuations due to adverse events in the tapinarof groups than with vehicle. LIMITATIONS: Long-term efficacy was not assessed. CONCLUSION: Tapinarof demonstrated highly significant efficacy and favorable safety and tolerability in a diverse population of patients with AD down to 2 years of age.

Risk factors and outcomes of melanoma in children and adolescents: A retrospective multicenter study.

BACKGROUND: Pediatric melanoma presents with distinct clinical features compared to adult disease. OBJECTIVE: Characterize risk factors and negative outcomes in pediatric melanoma. METHODS: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers. RESULTS: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls. LIMITATIONS: Retrospective nature, cohort size, control selection, and potential referral bias. CONCLUSION: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma.

Approach to Mycosis Fungoides in children: Consensus-based recommendations.

BACKGROUND: Pediatric Mycosis fungoides (MF) management extrapolates from adult guidelines, despite differing clinical aspects. Recommendations are essential to address unique challenges in this distinct patient group. OBJECTIVE: This project aims to derive consensus recommendations for pediatric MF management. METHODS: Experts from pediatric dermatology, general dermatology, dermatopathology, and pediatric hematology-oncology (N = 83) were invited to contribute to consensus recommendations. The process involved 3 electronic Delphi rounds, concluding with a final consensus meeting using a modified Nominal Group Technique for unresolved items. RESULTS: Consensus included more clinical severity measures than tumor-node-metastasis-blood staging: pruritus, functional or esthetic impairment (eg, palms, soles, genitalia), quality of life impact, and psychological aspects (eg, embarrassment, anxiety, depression), plus parental anxiety. Ten recommendations were made for managing early and advanced pediatric MF. Disagreement emerged in choosing therapies beyond stage I of the disease. DISCUSSION: This multinational initiative aimed to standardize optimal pediatric MF management and successfully generated consensus recommendations. Additional work is needed for structured, prospective protocols in advanced-stage pediatric MF. LIMITATIONS: Lack of pediatric hematologists-oncologists and patients' representatives. CONCLUSION: Documentation of extended clinical severity and outcome measures is recommended. Addressing the need for structured protocols in advanced-stage pediatric MF and implementing systematic, prospective data collection is crucial.

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 16-Week Trial to Evaluate the Efficacy and Safety of FB-401 in Children, Adolescents, and Adult Subjects (Ages 2 Years and Older) with Mild-to-Moderate Atopic Dermatitis.

BACKGROUND: Atopic dermatitis is a common chronic, relapsing, and remitting inflammatory skin disorder associated with cutaneous dysbiosis. Current treatment options often fail to adequately control the disease and have unfavorable safety profiles. There is a need for new options that address these treatment shortcomings. OBJECTIVE: The aim of the study was to evaluate the efficacy, safety, and tolerability of FB-401, a live therapeutic product of 3 strains of Roseomonas mucosa, compared to matching placebo applied topically 3 times per week to participants ages ≥2 years of age with mild-to-moderate atopic dermatitis. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. The primary outcome was the proportion of participants with 50% improvement in Eczema Area and Severity Index score from baseline at week 16. 154 subjects aged 2 or older with a clinical diagnosis of atopic dermatitis as defined by Hanifin and Rajka criteria with mild or moderate severity were randomized 1:1 via interactive web response system to FB-401 or placebo. RESULTS: The proportion of subjects who achieved the primary outcome was similar between both treatment groups, with no significant treatment group differences observed at any post-baseline visit. The number of treatment-emergent adverse events and the number of subjects with at least one were similar across treatment groups. One serious adverse event not related to treatment was reported. No treatment-emergent adverse events led to treatment discontinuation or study discontinuation. CONCLUSIONS: FB-401 showed an acceptable safety profile but failed to prove superior to placebo in treating children and adults with mild-to-moderate atopic dermatitis.

Systemic Therapy for Atopic Dermatitis in Children and Adolescents: A United States Expert Consensus.

Atopic dermatitis (AD) is a chronic, type-2 mediated, inflammatory skin disease characterized by intense pruritus, disruption of skin barrier function, and immune dysregulation. Management strategies for AD are routinely determined based on disease severity. First-line treatment begins with basic skin care and topical anti-inflammatory medication, which is typically sufficient for the management of mild-to-moderate disease. For those patients with moderate-to-severe disease, systemic therapy is often required. This can involve off-label treatment with conventional immunosuppressant medications. However, this approach is limited by a lack of robust clinical trial data and safety concerns that necessitate close monitoring. The emergence of novel targeted biologics and small molecules to treat AD presents an opportunity to optimize AD management and patient outcomes by offering greater efficacy than traditional immunosuppressants and a favorable safety profile. As the treatment landscape shifts, clinicians can benefit from a standardized process of patient assessment and treatment, along with resources to help maintain contemporary knowledge of available therapeutic options. This United States (US)-based, expert-led consensus used a modified Delphi process to develop core recommendations for the use of systemic medications for the management of pediatric patients <18 years of age with moderate-to-severe AD.

Hypothalamic-Pituitary-Adrenal Axis Response in Patients With Acne Vulgaris Treated With Clascoterone.

BACKGROUND: Clascoterone cream 1% is a topical androgen receptor inhibitor approved to treat acne vulgaris in patients =>12 years of age. This report provides details of patients who developed laboratory signs of hypothalamic-pituitary-adrenal (HPA) axis suppression without clinical signs of adrenal suppression during the clascoterone development program. METHODS: Two open-label, multicenter, Phase 2 trials evaluated HPA axis suppression in patients with moderate-to-severe acne vulgaris. Study 1 (NCT01831960) enrolled cohorts of adults =>18 years of age and adolescents =>12 to <18 years of age. Study 2 (NCT02720627) enrolled adolescents 9 to <12 years of age. Patients applied clascoterone twice daily at maximum-exposure dosages for 14 days. Adrenal suppression was evaluated via cosyntropin stimulation test (CST) at baseline and day 14. Patients with an abnormal CST result (serum cortisol level =<18 µg/dL) had a follow-up CST approximately 4 weeks later. Blood was collected for pharmacokinetic analysis. Other safety assessments included adverse events (AEs), physical examination/vital signs, and electrocardiography. RESULTS: Overall, 5/69 clascoterone-treated patients had an abnormal CST result on day 14, including 1/20 adults, 2/22 patients aged =>12 to <18 years, and 2/27 patients aged 9 to <12 years. All patients had normal cortisol levels at follow-up testing approximately 4 weeks later. No relationship was observed between abnormal CST results and clascoterone plasma concentrations or the amount of study drug applied. No clinically relevant AEs or clinically significant changes in safety measures were observed in patients with adrenal suppression. CONCLUSION: Clascoterone induced laboratory evidence of mild, reversible HPA axis suppression under maximum-use exposure. J Drugs Dermatol. 2024;23(6):433-437.     doi:10.36849/JDD.7997.

A Consensus on Staphylococcus aureus Exacerbated Atopic Dermatitis and the Need for a Novel Treatment.

The skin microbiome is essential for skin barrier function because it inhibits pathogen colonization, and decreased microbiome diversity correlates with increased Staphylococcus aureus (S. aureus) burden and atopic dermatitis (AD) severity. Managing S. aureuss-driven AD in clinical practice remains problematic due to complications such as AD exacerbation, impetigo, abscesses, and invasive infections. This project used a modified Delphi process comprising face-to-face discussions followed by a blinded vote to define 5 final consensus statements. A panel of 6 pediatric dermatologists developed a consensus on S. aureus-driven AD exacerbation, challenges in current treatments for AD with secondary bacterial infections, and new developments to improve patient care and outcomes. The panel's 5 consensus statements provide recommendations for dermatologists, pediatricians, and healthcare providers treating patients with secondary infected AD. These recommendations underscore the importance of recognizing and managing S. aureus skin infection in AD clinical practice and promoting antibiotic stewardship to mitigate resistance. The panel defined a significant unmet need for a single topical AD therapy effective against all symptoms, including pruritus, S. aureus-driven AD exacerbation, infection, and inflammation, across AD severity levels. J Drugs Dermatol. 2024;23(10):825-832. doi:10.36849/JDD.8240.

Triple-Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Acne in Adult and Pediatric Participants.

BACKGROUND: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel (CAB) is the first fixed-dose triple-combination approved for the treatment of acne. This post hoc analysis investigated the efficacy and safety of CAB in pediatric (<18 years) and adult (greater than or equal to 18 years) participants. METHODS: In two multicenter, double-blind, phase 3 studies (NCT04214639 and NCT04214652), participants greater than or equal to 9 years of age with moderate-to-severe acne were randomized (2:1) to 12 weeks of once-daily treatment with CAB or vehicle gel. Pooled data were analyzed for pediatric and adult subpopulations. Assessments included treatment success (greater than or equal to 2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 0 [clear] or 1 [almost clear], inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. RESULTS: At week 12, treatment success rates for both pediatric and adult participants were significantly greater with CAB (52.7%; 45.9%) than with vehicle (24.0%; 23.5%; P<0.01, both). CAB-treated participants in both subgroups experienced greater reductions from baseline versus vehicle in inflammatory (pediatric: 78.6% vs 50.4%; adult: 76.6% vs 62.8%; P<0.001, both) and noninflammatory lesions (pediatric: 73.8% vs 41.1%; adult: 70.7% vs 52.2%; P<0.001, both). Acne-QoL improvements from baseline to week 12 were significantly greater with CAB than with a vehicle. Most TEAEs were of mild-to-moderate severity; no age-related trends for safety/tolerability were observed.  Conclusions: CAB gel demonstrated comparable efficacy, quality of life improvements, and safety in pediatric and adult participants with moderate-to-severe acne. As the first fixed-dose, triple-combination topical formulation, CAB represents an important new treatment option for patients with acne. J Drugs Dermatol. 2024;23(6):394-402.     doi:10.36849/JDD.8357.

Targeting the Aryl Hydrocarbon Receptor to Address the Challenges of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic relapsing–remitting disease with a multifactorial etiology involving epidermal barrier and immunologic dysfunction. Topical therapies form the mainstay of AD treatment, but options are limited by adverse effects and restrictions on application site, duration, and extent of use. Tapinarof (VTAMA; Dermavant Sciences, Inc.) is a first-in-class, non-steroidal, topical aryl hydrocarbon receptor (AhR) agonist approved for the treatment of plaque psoriasis. AhR is a ligand-dependent transcription factor with wide-ranging roles, including regulation of homeostasis and immune response in skin cells. AhR expression and signaling are altered in many inflammatory skin diseases, and clinical trials with tapinarof have validated AhR as a therapeutic target capable of delivering significant efficacy. Tapinarof cream 1% once daily demonstrated efficacy versus vehicle in adults and adolescents with AD and is being investigated in the ADORING trials for the treatment of AD in adults and children down to 2 years of age. J Drugs Dermatol. 2024;23(2):23-28.  doi:10.36849/JDD.8026.

Integrated Short-Term and Long-Term Efficacy of Topical Clascoterone Cream 1% in Patients Aged 12 Years or Older With Acne Vulgaris.

BACKGROUND: Clascoterone cream 1% is approved for the treatment of acne vulgaris in patients aged 12 years or older based on results from two identical pivotal Phase 3 trials. Integrated efficacy of clascoterone in patients aged 12 years or older with acne vulgaris from the pivotal trials (NCT02608450 and NCT02608476) and long-term extension (LTE) study (NCT02682264) is reported. METHODS: In the pivotal trials, patients with moderate-to-severe acne vulgaris were randomized 1:1 to twice-daily application of clascoterone cream 1% or vehicle for 12 weeks; they could then enter the LTE study, where all patients applied clascoterone to the face and, if desired, trunk for up to 9 additional months. Efficacy was assessed from treatment success based on Investigator's Global Assessment scores (IGA 0/1) in patients aged 12 years or older in the intention-to-treat population; lesion counts were assessed through week 12. Missing data were handled using multiple imputation in the pivotal studies and were not imputed in the LTE study. RESULTS: Of 1421 patients enrolled, 1143 (clascoterone, 576; vehicle, 567) completed week 12; 600 entered and 343 completed the LTE study. The treatment success rate and most lesion count reductions following clascoterone vs placebo treatment reached statistical significance at week 12; the overall treatment success rate increased to 30.2% for facial acne after 12 months and 31.7% for truncal acne after 9 months of treatment. CONCLUSIONS: The efficacy of clascoterone cream 1% for the treatment of acne vulgaris continued to increase over time for up to 12 months in patients aged 12 years or older with acne vulgaris.   J Drugs Dermatol. 2024;23(1):1278-1283.     doi:10.36849/JDD.7719.

Successful topical minoxidil treatment for hair density and length in trichorhinophalangeal syndrome type 1.

A 9-year-old girl presented with slow hair growth and hair thinning since birth. Additionally, she had short stature and abnormally short fingers; genetic testing confirmed the diagnosis of trichorhinophalangeal syndrome (TRPS) type 1. After 4 months of topical minoxidil treatment, hair density and length significantly improved diffusely throughout the scalp without evidence of hypertrichosis. This case underscores the therapeutic potential of topical minoxidil for TRPS, paving the way for improved patient quality of life.

Tralokinumab therapy for moderate-to-severe atopic dermatitis: Clinical outcomes with targeted IL-13 inhibition.

Atopic dermatitis (AD) is a chronic, inflammatory, intensely pruritic skin disorder associated with significant patient burden. Interleukin (IL)-13 is a cytokine that acts as a driver of immune dysregulation, skin-barrier dysfunction, and microbiome dysbiosis that characterizes AD, and is consistently overexpressed in AD skin. Tralokinumab is a fully human immunoglobulin (Ig) G4 monoclonal antibody that binds specifically to IL-13 with high affinity, thereby inhibiting subsequent downstream IL-13 signaling. Three pivotal phase 3 clinical trials demonstrated that tralokinumab 300 mg every other week, as monotherapy or in combination with topical corticosteroids as needed, provides significant improvements in signs and symptoms of moderate-to-severe AD, as measured by Investigator's Global Assessment 0/1 (clear/almost clear) and Eczema Area and Severity Index-75 at Week 16. Improvements were observed soon after tralokinumab initiation and were maintained over 52 weeks of therapy. Tralokinumab significantly improved patient-reported outcomes such as itch and sleep, and demonstrated a safety profile comparable with placebo; conjunctivitis during tralokinumab therapy was generally mild. Similar results were observed in a phase 3 adolescent trial. The role of IL-13 in the pathophysiology of AD justifies a targeted approach and a wealth of clinical data supports tralokinumab as a new therapeutic option for people with moderate-to-severe AD.

Efficacy and safety of baricitinib in combination with topical corticosteroids in paediatric patients with moderate-to-severe atopic dermatitis with an inadequate response to topical corticosteroids: results from a phase III, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS).

BACKGROUND: Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, is approved in many countries for moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. OBJECTIVES: To evaluate the efficacy and safety of three doses of baricitinib in combination with low-to-moderate potency topical corticosteroids in paediatric patients with moderate-to-severe AD. METHODS: Patients (aged 2 to < 18 years) were randomized (1 : 1 : 1 : 1) to once-daily baricitinib low dose (1 mg equivalent), medium dose (2 mg equivalent), high dose (4 mg equivalent) or placebo for 16 weeks. The primary endpoint was the proportion of patients achieving a validated Investigator Global Assessment® (vIGA-AD) of 0/1 with a ≥ 2-point improvement at week 16. Key secondary endpoints included the proportions of patients achieving ≥ 75% and ≥ 90% improvement in the Eczema Area and Severity Index (EASI-75 and EASI-90, respectively), ≥ 75% improvement in the SCORing Atopic Dermatitis (SCORAD 75), mean change from baseline in EASI score and proportion of patients achieving a 4-point improvement in the Itch Numeric Rating scale (NRS) for patients aged ≥ 10 years. Primary and key secondary efficacy analyses were conducted on the intent-to-treat population and adjusted for multiplicity. Safety analyses included all randomized patients who received ≥ 1 dose of study treatment. RESULTS: A total of 483 patients were randomized (mean age 12 years). The baricitinib 4 mg equivalent achieved a statistically significant (P < 0.05) improvement vs. placebo on all 16-week endpoints (vIGA 0/1 with ≥ 2-point improvement, EASI-75, EASI-90, SCORAD 75, mean change in EASI score and Itch NRS 4-point improvement for patients aged ≥ 10 years). Improvement (P < 0.05, non-multiplicity adjusted) was also observed for baricitinib 4 mg equivalent vs. placebo in the ability to fall asleep and in reduction of topical corticosteroid use. Few patients discontinued due to adverse events (1.6% for placebo and 0.6% for those treated with baricitinib). There were no deaths, venous thromboembolic events, arterial thrombotic events, major adverse cardiovascular events, malignancies, gastrointestinal perforations or opportunistic infections seen. CONCLUSIONS: The results indicate that baricitinib offers a potential therapeutic option with a favourable benefit-risk profile for paediatric patients with moderate-to-severe AD who are candidates for systemic therapies.

DMT310, a novel once-weekly topical treatment for patients with moderate-to-severe acne vulgaris: Results of a phase 2b randomized, double-blind, placebo-controlled trial.

BACKGROUND: Poor patient adherence with antiacne medications is a common clinical challenge. DMT310, a natural, topical product with a once-weekly application schedule, may alleviate this obstacle. OBJECTIVE: Evaluate the safety, tolerability, and efficacy of DMT310 in treating moderate-to-severe acne. METHODS: This 12-week, randomized, double-blind, placebo-controlled, multicenter clinical trial enrolled participants 12 years and older with moderate-to-severe acne. RESULTS: The intent-to-treat population included a total of 181 participants (DMT310, N = 91; placebo, N = 90). Participants who received DMT310 vs participants treated with placebo demonstrated a statistically significant greater reduction in the number of inflammatory and noninflammatory lesions at all time points: inflammatory lesion counts at week 12 (-15.64 vs -10.84, P < .001); noninflammatory lesion counts at week 12 (-18.26 vs -12.41, P < .001). DMT310-treated participants also had higher rates of Investigator's Global Assessment treatment success than participants in the placebo group at all time points: Investigator's Global Assessment at week 12 (44.40% vs 17.78%; P < .001). No serious treatment related adverse events occurred. CONCLUSIONS: DMT310 once-weekly topical treatment significantly reduced both inflammatory and noninflammatory lesions and yielded a greater proportion of Investigator's Global Assessment treatment success at all time points in participants with moderate-to-severe acne.

Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: Results from two phase 3 studies.

BACKGROUND: Ruxolitinib cream demonstrated safety and efficacy over 8 weeks in 2 double-blind phase 3 atopic dermatitis studies (NCT03745638/NCT03745651). OBJECTIVE: To evaluate long-term safety (LTS) and disease control with ruxolitinib cream. METHODS: Patients initially randomized to twice-daily 0.75%/1.5% ruxolitinib cream maintained their regimen during the 44-week LTS period (as-needed treatment). Patients on vehicle were rerandomized (1:1) at week 8 to either ruxolitinib cream strength. Safety and disease control (Investigator's Global Assessment score 0/1 and affected body surface area) were assessed. RESULTS: Over 52 weeks, adverse events were reported in 67.4%/62.6%/53.5%/57.6% of patients in 0.75%/1.5% ruxolitinib cream/vehicle to 0.75% ruxolitinib cream/vehicle to 1.5% ruxolitinib cream groups (n = 426/446/101/99). Most common adverse events were upper respiratory tract infection (10.3%/11.4%/5.9%/7.1%) and nasopharyngitis (8.9%/9.9%/7.9%/14.1%). Most adverse events were considered unrelated to treatment. Application site reactions were infrequent (3.8%/1.8%/1.0%/1.0%). Disease control was achieved throughout the LTS; 74.1% to 77.8% of patients had Investigator's Global Assessment 0/1 at week 52, and mean affected body surface area was low (1.4%-1.8%). LIMITATIONS: LTS had no control treatment. CONCLUSION: During 44 weeks of as-needed treatment, ruxolitinib cream demonstrated effective disease control and tolerability; low ruxolitinib plasma concentrations alongside safety findings reflecting known risk factors suggest physiologically meaningful systemic Janus kinase inhibition is highly unlikely.

Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: Analysis of microbial diversity in ECZTRA 1, a randomized controlled trial.

BACKGROUND: Atopic dermatitis (AD) is characterized by microbial dysbiosis, immune dysregulation, and an impaired skin barrier. Microbial dysbiosis in AD involves a reduction in diversity primarily driven by an increased abundance of Staphylococcus aureus. Tralokinumab, an approved treatment for adults with moderate-to-severe AD, improves the skin barrier and immune abnormalities by specifically targeting the interleukin 13 cytokine, but its impact on the skin microbiome is unknown. OBJECTIVE: To investigate how tralokinumab affects the skin microbiome by examining the lesional skin of adults with moderate-to-severe AD from the phase 3 ECZTRA 1 trial (NCT03131648). METHODS: Microbiome profiling, S aureus abundance, and biomarker data were assessed in a subset of ECZTRA 1 participants (S aureus abundance at baseline and week 16; microbiome profiling at baseline, and week 8/16; and serum sampling before dose and week 4/8/16/28/52). RESULTS: Tralokinumab treatment led to increased microbial diversity, reduced S aureus abundance, and increased abundance of the commensal coagulase-negative Staphylococci. LIMITATIONS: Limitations include a lack of S aureus abundance data at week 8, sampling site variation between participants, and possible influence from concomitant systemic antiinfectives. CONCLUSION: Our findings indicate specific targeting of the interleukin 13 cytokine with tralokinumab can directly and/or indirectly improve microbial dysbiosis seen in AD skin.

Prevalence and burden of atopic dermatitis involving the head, neck, face, and hand: A cross sectional study from the TARGET-DERM AD cohort.

BACKGROUND: Atopic dermatitis (AD) is severely burdensome, and there has been poor characterization of any differences in impact based on the area affected. OBJECTIVE: To estimate the prevalence and HRQoL impact of head/face/neck/hand (HFNH) involvement among patients with moderate-to-severe atopic dermatitis. METHODS: All TARGET-DERM AD registry patients with moderate/severe Investigator Global Assessment (vIGA-AD) were assessed using the Patient Oriented SCORing Atopic Dermatitis, Patient Oriented Eczema Measure (POEM) and the (Children's) Dermatology Life Quality Index ((C)DLQI). RESULTS: 541 participants met the criteria (75.0% adults) and 84% (N = 453) reported HFNH involvement. HFNH and non-HFNH involved participants had similar characteristics; 55.2% female and 46.9% White. Compared to the non-HFNH involved, the involved had severe vIGA-AD (28.5% vs 16.3%, P = .02) and higher median body surface area affected (15% vs 10%, P ≤ .01) and were twice as likely to have higher (C)DLQI and POEM scores. LIMITATIONS: This was an analysis of real-world and patient reported outcome data. CONCLUSION: Real-world HFNH involved AD patients were associated with significantly worse quality of life, POEM/(C)DLQI, and more severe disease. Detailed assessments of specific areas affected by AD are needed to personalize treatment.