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Importance: Safe and effective long-term treatments for adolescents with moderate to severe atopic dermatitis (AD) are limited., Objective: To evaluate the efficacy and safety of interleukin-13-targeted treatment with tralokinumab monotherapy in adolescents with AD., Design, Setting, and Participants: The 52-week, randomized, double-blinded, placebo-controlled, phase 3 ECZTRA 6 trial was conducted from July 17, 2018, through March 16, 2021, at 72 centers across 10 countries in North America, Europe, Asia, and Australia. Enrolled patients were 12 to 17 years old with moderate to severe AD (Investigator's Global Assessment [IGA] score ≥3; Eczema Area and Severity Index [EASI] ≥16)., Interventions: Patients were randomized (1:1:1) to tralokinumab (150 or 300 mg) or placebo every 2 weeks for 16 weeks. Patients with an IGA score of 0 (clear) or 1 (almost clear) and/or 75% or higher improvement in EASI (EASI 75) at week 16 without rescue medication received maintenance treatment; other patients switched to open-label tralokinumab, 300 mg, every 2 weeks., Main Outcomes and Measures: Primary end points at week 16 were an IGA score of 0 or 1 and/or achieving EASI 75. Key secondary end points were a reduction of Adolescent Worst Pruritus Numeric Rating Scale of 4 or more, change in SCORing AD, and change in Children's Dermatology Life Quality Index from baseline to week 16. Safety end points were the number of adverse events and serious adverse events., Results: Of 301 patients randomized, 289 comprised the full analysis set (median [IQR] age, 15.0 [13.0-16.0] years; 149 [51.6%] male). More patients receiving tralokinumab, 150 mg, (n = 98), and tralokinumab, 300 mg (n = 97), achieved an IGA score of 0 or 1 without rescue medication at week 16 (21 [21.4%] and 17 [17.5%], respectively) vs placebo (n = 94; 4 [4.3%]) (adjusted difference, 17.5% [95% CI, 8.4%-26.6%]; P < .001 and 13.8% [95% CI, 5.3%-22.3%]; P = .002, respectively). More patients receiving tralokinumab, 150 mg (28 [28.6%]), and tralokinumab, 300 mg, (27 [27.8%]) vs placebo (6 [6.4%]) achieved EASI 75 without rescue at week 16 (adjusted difference, 22.5% [95% CI, 12.4%-32.6%]; P < .001 and 22.0% [95% CI, 12.0%-32.0%]; P < .001, respectively). Proportions of patients with Adolescent Worst Pruritus Numeric Rating Scale reduction of 4 or more from baseline were greater with tralokinumab, 150 mg (23.2%), and tralokinumab, 300 (25.0%), vs placebo (3.3%), and adjusted mean changes were greater in SCORing AD with tralokinumab, 150 mg (-27.5), and tralokinumab, 300 mg (-29.1), vs placebo (-9.5) and in Children's Dermatology Life Quality Index with tralokinumab, 150 mg (-6.1), and tralokinumab, 300 mg (-6.7), vs placebo (-4.1) at week 16. At week 52, tralokinumab efficacy was maintained without rescue in more than 50% of patients meeting primary end point(s) at week 16. In the open-label phase, IGA score of 0 or 1 and EASI 75 were achieved in 33.3% and 57.8%, respectively, at week 52. Tralokinumab was well tolerated, without frequency of conjunctivitis increasing through week 52., Conclusions and Relevance: In this randomized clinical trial, tralokinumab was efficacious and well tolerated, supporting its value for treating adolescents with moderate to severe AD., Trial Registration: ClinicalTrials.gov Identifier: NCT03526861.

Introduction: Inflammatory skin disorders compromise skin barrier health. Early and daily skincare use aims to maintain a life-long healthy skin barrier. Racial/ethnic and age variations in skin barrier properties, cultural differences, and clinical presentation of the inflammatory skin disorder influence the choice of treatment and skin care. Ceramide-containing skin care may play a role in restoring and maintaining a healthy skin barrier., Methods: A panel of 6 dermatologists met to develop consensus statements based on their 8 previous publications on promoting skin barrier health throughout life using ceramide-containing skin care. The publications covered skin barrier integrity in the newborn and infant, and the role of the skin barrier in mitigating atopic dermatitis (AD); racial/ethnic variations in the skin barrier and implications for skin care; the role of the skin barrier in inflammatory skin conditions including acne, AD and psoriasis in skin of color (SOC) populations; skin barrier integrity in patients with rosacea; and xerosis in patients with diabetes mellitus. The panel synthesized the 8 publications, selected information from a literature review, and their expert opinions and experiences to create the statements. The consensus was reached through a modified Delphi method where the panel met face-to-face and followed up virtually., Results: The panel adopted 6 consensus statements highlighting the importance of skin care in restoring/maintaining a healthy skin barrier in the populations mentioned above. Skin care suited to this role is gentle, has near-physiologic pH, is pleasant to use, and contains ceramides. This type of skin care can promote a healthy skin barrier and attenuate or delay inflammatory skin conditions., Conclusions: Adjunctive daily skin care throughout life promotes a healthy skin barrier and is beneficial in managing various inflammatory skin disorders in all populations. However, when choosing optimal treatment and skin care, physicians should consider variations in age, skin properties, presentation of the condition, and cultural differences. J Drugs Dermatol. 2023;22:2(Suppl 1):s3-14.

Background: Observational studies suggest an increased risk of eczema in children living in hard versus soft water areas, and there is, therefore, an interest in knowing whether softening water may prevent eczema. We evaluated the feasibility of a parallel-group assessor-blinded pilot randomized controlled trial to test whether installing a domestic ion-exchange water softener before birth in hard water areas reduces the risk of eczema in infants with a family history of atopy., Methods: Pregnant women living in hard water areas (>250 mg/L calcium carbonate) in and around London UK, were randomized 1:1 antenatally to either have an ion-exchange water softener installed in their home or not (ie to continue to receive usual domestic hard water). Infants were assessed at birth and followed up for 6 months. The main end-points were around feasibility, the primary end-point being the proportion of eligible families screened who were willing and able to be randomized. Clinical end-points were evaluated including frequency of parent-reported doctor-diagnosed eczema and visible eczema on skin examination. Descriptive analyses were conducted, and no statistical testing was performed as this was a pilot study., Results: One hundred and forty-nine families screened were eligible antenatally and 28% (41/149) could not have a water softener installed due to technical reasons or lack of landlord approval. Eighty of 149 (54%) were randomized, the primary end-point. Two participants withdrew immediately after randomization, leaving 39 participants in each arm (78 total). Attrition was 15% (12/78) by 6 months postpartum. All respondents (n = 69) to the study acceptability questionnaire reported that the study was acceptable. Fifty-six of 708 (7.9%) water samples in the water softener arm were above the hard water threshold of 20 mg/L CaCO 3 . At 6 months of age 27/67 infants (40%) developed visible eczema, 12/36 (33%) vs. 15/31 (48%) in the water softener and control groups, respectively, difference -15% (95% CI -38, 8.3%), with most assessments (≥96%) remaining blinded. Similarly, a lower proportion of infants in the water softener arm had parent-reported, doctor-diagnosed eczema by 6 months compared to the control arm, 6/17 (35%) versus 9/19 (47%), difference -12% (95% CI -44, 20%)., Conclusion: A randomized controlled trial of water softeners for the prevention of atopic eczema in high-risk infants is feasible and acceptable., Trial Registration: NCT03270566 (clinicaltrials.gov)., (© 2021 John Wiley & Sons Ltd.)

Background: A significant improvement in clinical signs was demonstrated with abrocitinib relative to placebo in adolescents with moderate-to-severe atopic dermatitis (AD) in three phase 3, randomized, double-blinded, placebo-controlled studies (JADE TEEN [ClinicalTrials.gov, NCT03796676], JADE MONO-1 [NCT03349060] and JADE MONO-2 [NCT03575871])., Objectives: To evaluate the impact of abrocitinib on patient-reported signs/symptoms, including sleep loss and quality of life among adolescents with moderate-to-severe AD., Methods: JADE TEEN, JADE MONO-1 and JADE MONO-2 were conducted in the Asia-Pacific region, Europe and North America and included patients aged 12-17 years with moderate-to-severe AD and inadequate response to ≥ 4 consecutive weeks of topical medication or treatment with systemic therapy for AD. Patients were randomly assigned (1 : 1 : 1, JADE TEEN; 2 : 2 : 1, JADE MONO-1/-2) to receive once-daily oral abrocitinib (200 or 100 mg) or placebo for 12 weeks in combination with topical therapy (JADE TEEN) or as monotherapy (JADE MONO-1/-2). Data from adolescent patients in JADE MONO-1/-2 were pooled for these analyses., Results: At week 12, more adolescents treated with abrocitinib (200 or 100 mg) vs. placebo achieved a ≥ 4-point improvement from baseline in the Patient-Oriented Eczema Measure in JADE TEEN (83.9% and 77.0% vs. 60.2%) and JADE MONO-1/-2 (83.0% and 69.4% vs. 43.5%) and a ≥ 6-point improvement from baseline in the Children's Dermatology Life Quality Index in JADE TEEN (73.8% and 67.5% vs. 56.5%) and JADE MONO-1/-2 (70.0% and 57.1% vs. 19.0%). Significant improvements in SCORing Atopic Dermatitis Visual Analog Scale for sleep loss scores were demonstrated with abrocitinib vs. placebo at weeks 2-12 in JADE TEEN and JADE MONO-1/-2., Conclusions: Patient-reported signs/symptoms, including reduction of sleep loss and quality of life, were substantially improved with abrocitinib monotherapy or combination therapy relative to placebo in adolescents with moderate-to-severe AD., (© 2021 Pfizer Inc.. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Dupilumab, a monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits IL-4/IL-13 signalling is indicated in dermatology for the treatment of moderate-to-severe atopic dermatitis (AD) in adult and adolescent patients 12 years and older and severe AD in children 6-11 years, who are candidates for systemic therapy. Dupilumab received Early Access to Medicines Scheme (EAMS) approval for adults in March 2017., Objectives: The purpose of this study was to assess the efficacy outcomes of treatment with dupilumab in EAMS., Methods: A retrospective analysis of adult patients enrolled in the dupilumab EAMS in the UK. Scores were assessed at baseline and follow up, including the Eczema Area and Severity Index (EASI), Investigator's Global Assessment Score (IGA) and Dermatology Life Quality Index (DLQI)., Results: Data were available for 57 adult patients treated with dupilumab for at least 12 weeks; 73.6% of patients had received prior treatment with 3 or 4 immunosuppressants. Baseline scores for the EASI and DLQI were 27.93 (standard deviation, SD 13.09) and 18.26 (SD 6.18) respectively. AD severity scores showed statistically significant improvement at week 16±4 weeks (p <0.001 for all). The mean change in EASI was 14.13 points with 66.7% and 36.7% achieving a 50% (EASI-50) and 75% (EASI-75) improvement in EASI, respectively at 16 +/- 4 weeks. IGA scores improved by at least two categories for 75% patients. DLQI scores decreased by a mean of 9.0 points, with 80% patients demonstrating a MCID 4-point improvement. For 85% patients, clinicians rated the treatment response as being either 'better' (19%) or 'much better' (65%)., Conclusions: Dupilumab is associated with a significant and clinically relevant improvements in AD as measured by patient- and physician-reported outcome measures. Importantly, the clinical efficacy, despite the refractory disease of this EAMS cohort, is comparable to that previously reported in clinical trials., Competing Interests: Conflicts of interest LD, RR and RH are employees of and hold stock options in Sanofi Genzyme. DOK has received honoraria as a speaker and /or advisory board member for Abbvie, Novartis, Lilly, UCB and Janssen. MAJ has received honoraria and/or grants as an investigator speaker, and/or advisory board member for AbbVie, Amgen Lilly, Sanofi, Leo Pharma and Pfizer. PL has received honoraria and/or grants as an investigator, speaker, and/ or advisory board member for AbbVie, Almirall, Actelion, Celgene, Janssen, Lilly, Sanofi, Leo, UCB and Novartis. LS has no conflicts of interest. MC has received honoraria and or grants as an investigator, speaker, and/or advisory board member for Eli Lily, Leo Pharma, Novartis, L’Oreal, Procter and Gamble, Oxagen, Johnson & Johnson, Pfizer, Regeneron Sanofi, UCB and Hyphens Pharma. SV has received an educational grant from Abbvie. HC has received honoraria for advisory board participation from Sanofi, Abbvie, Novartis and Janssen., (Copyright © 2021 Ulster Medical Society.)

Background: Children aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16-week, randomized, placebo-controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)-4/IL-13 signalling, significantly improved signs and symptoms with acceptable safety; longer-term safety and efficacy data are lacking., Objectives: To report the pharmacokinetic profile and long-term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD., Methods: Children (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study and subsequent open-label extension (OLE) study. Patients received single-dose dupilumab 2 or 4 mg kg -1 followed by 8-week pharmacokinetic sampling, then 2 or 4 mg kg -1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration-time profile and treatment-emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus Numeric Rating Scale (PP-NRS) score., Results: Of 38 children enrolled, 37 completed phase IIa and 33 continued to the OLE. Nonlinear, target-mediated pharmacokinetics characterized dupilumab concentrations (week 24-48 mean serum concentrations: 2 mg kg -1 , 61-77 mg L -1 ; 4 mg kg -1 , 143-181 mg L -1 ). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. The most commonly reported TEAEs were nasopharyngitis (2 mg kg -1 , 47%; 4 mg kg -1 , 56%) and AD exacerbation (29% and 13%, respectively). Single-dose dupilumab rapidly improved AD with further improvements through week 52. Mean EASI and PP-NRS improved by -37%/-33% and -17%/-20% at week 2 (phase IIa) and -92%/-84% and -70%/-58% at week 52 (OLE), respectively., Conclusions: These safety and efficacy results support the use of dupilumab as a continuous long-term treatment for children aged ≥ 6 to < 12 years with severe AD., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Objective: Eczema and food allergy start in infancy and have shared genetic risk factors that affect skin barrier. We aimed to evaluate whether skincare interventions can prevent eczema or food allergy., Design: A prospectively planned individual participant data meta-analysis was carried out within a Cochrane systematic review to determine whether skincare interventions in term infants prevent eczema or food allergy., Data Sources: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to July 2020., Eligibility Criteria for Selected Studies: Included studies were randomized controlled trials of infants <1 year with healthy skin comparing a skin intervention with a control, for prevention of eczema and food allergy outcomes between 1 and 3 years., Results: Of the 33 identified trials, 17 trials (5823 participants) had relevant outcome data and 10 (5154 participants) contributed to IPD meta-analysis. Three of seven trials contributing to primary eczema analysis were at low risk of bias, and the single trial contributing to primary food allergy analysis was at high risk of bias. Interventions were mainly emollients, applied for the first 3-12 months. Skincare interventions probably do not change risk of eczema by age 1-3 years (RR 1.03, 95% CI 0.81, 1.31; I 2 =41%; moderate certainty; 3075 participants, 7 trials). Sensitivity analysis found heterogeneity was explained by increased eczema in a trial of daily bathing as part of the intervention. It is unclear whether skincare interventions increase risk of food allergy by age 1-3 years (RR 2.53, 95% CI 0.99 to 6.47; very low certainty; 996 participants, 1 trial), but they probably increase risk of local skin infections (RR 1.34, 95% CI 1.02, 1.77; I 2 =0%; moderate certainty; 2728 participants, 6 trials)., Conclusion: Regular emollients during infancy probably do not prevent eczema and probably increase local skin infections., (© 2021 John Wiley & Sons Ltd.)

Background: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms., Objectives: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments., Methods: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885., Results: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period., Conclusions: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Dupilumab has demonstrated efficacy and acceptable safety in adults and children (aged 6-17 years) with moderate-to-severe atopic dermatitis (AD), but effective systemic therapy with a favorable risk-benefit profile in younger children remains a significant unmet need., Objectives: To determine the pharmacokinetics, safety and efficacy of single-dose dupilumab in children with severe AD aged ≥6 months to <6 years., Methods: This open-label, multicenter, phase 2, sequential, two-age cohort, two-dose level study (LIBERTY AD PRE-SCHOOL; NCT03346434) included an initial cohort of older children aged ≥2 to <6 years, followed by a younger cohort aged ≥6 months to <2 years. Pharmacokinetic sampling, safety monitoring and efficacy assessments were performed during the 4-week period after a single subcutaneous injection of dupilumab, in two sequential dosing groups (3 mg/kg, then 6 mg/kg). The use of standardized, low-to-medium potency topical corticosteroids was allowed., Results: Forty patients were enrolled (20/age cohort, 10/dose level within a cohort) between December 20, 2017 and July 22, 2019. Within each age cohort, pharmacokinetic exposures after a single injection of dupilumab increased in a greater than dose-proportional manner. At week 3, treatment with 3 and 6 mg/kg dupilumab reduced scores of mean Eczema Area and Severity Index by -44.6% and -49.7% (older cohort) and -42.7% and -38.8% (younger cohort), and mean Peak Pruritus NRS scores by -22.9% and -44.7% (older cohort) and -11.1% and -18.2% (younger cohort), respectively. At week 4, improvements in most efficacy outcomes diminished in both age groups, particularly with the lower dose. The safety profile was comparable to that seen in adults, adolescents and children., Conclusions: Single-dose dupilumab was generally well tolerated and substantially reduced clinical signs/symptoms of AD. Slightly better responses were seen in older than younger children. The pharmacokinetics of dupilumab were non-linear, consistent with previous studies in adults and adolescents., (© 2020 Regeneron Pharmaceuticals, Inc. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier-stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti-inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid-potency corticosteroids are proven agents for proactive therapy, which is defined as the long-term intermittent anti-inflammatory therapy of frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit-risk ratio. The IL-4R-blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side-effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) only have limited effects on AD-related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient-specific, and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. Efficacy-proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults., (© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis., Methods: In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060., Findings: Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported., Interpretation: Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis., Funding: Pfizer., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Dupilumab (monoclonal antibody inhibiting IL-4/IL-13 signalling) is approved for use in adolescents aged ≥ 12 years with inadequately controlled moderate-to-severe atopic dermatitis (AD). Dupilumab significantly improved AD signs/symptoms in a 16-week, randomised, placebo-controlled phase III trial in adolescents (NCT03054428)., Objectives: To characterize the pharmacokinetics of dupilumab, and long-term safety and efficacy in adolescents., Methods: This was a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study with a phase III open-label extension (OLE) in adolescents with moderate-to-severe AD. In the phase IIa study, patients received one dupilumab dose (2 mg kg -1 or 4 mg kg -1 ) and 8 weeks of pharmacokinetic sampling. Thereafter, patients received the same dose weekly for 4 weeks, with 8-week safety follow-up. Patients then enrolled in the OLE, continuing 2 mg kg -1 or 4 mg kg -1 dupilumab weekly. Primary end points were dupilumab concentration-time profile and incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included Eczema Area and Severity Index (EASI)., Results: Forty adolescents received dupilumab in the phase IIa study; 36 enrolled in the OLE. Dupilumab showed nonlinear, target-mediated pharmacokinetics. Mean ± SD trough dupilumab concentrations in serum at week 48 (OLE) were 74 ± 19 mg L -1 and 161 ± 60 mg L -1 for 2 mg kg -1 and 4 mg kg -1 , respectively. Dupilumab was well tolerated over 52 weeks; the most common TEAEs were nasopharyngitis (week 52: 41% [2 mg kg -1 ], 47% [4 mg kg -1 ]) and AD exacerbation (29%, 42%). After one dupilumab dose in the phase IIa study, EASI improved from baseline to week 2 [mean ± SD reduction -34% ± 20% (2 mg kg -1 ) and -51% ± 29% (4 mg kg -1 )]. With continuing treatment, EASI scores improved further [week 52: -85% ± 12% (2 mg kg -1 ) and -84% ± 20% (4 mg kg -1 )]., Conclusions: In adolescents with moderate-to-severe AD, dupilumab's pharmacokinetic profile was similar to that in adults. These 52-week safety and efficacy data support long-term use of dupilumab in this patient population. What's already known about this topic? Adolescents with moderate-to-severe atopic dermatitis (AD) have high unmet medical need, with significant disease burden and limited treatment options. Dupilumab (monoclonal antibody against interleukin-4 receptor α) is approved for the treatment of adolescents with moderate-to-severe AD who are inadequately responsive to standard of care (U.S.A.) or candidates for systemic therapy (European Union). A 16-week, randomized, placebo-controlled phase III trial in adolescents demonstrated significant improvements in AD signs/symptoms with an acceptable safety profile. What does this study add? These studies demonstrate the long-term safety and efficacy of dupilumab in adolescents with moderate-to-severe AD for up to 52 weeks of treatment, thus extending and reinforcing the findings from the 16-week dupilumab phase III trial. The data from these studies also support the use of dupilumab in combination with current standard of care (topical corticosteroids), which was not evaluated in the 16-week phase III monotherapy trial., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate-to-severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate-to-severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate-to-severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo., Objectives: To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials., Methods: We evaluated randomized placebo-controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47)., Results: In most AD trials, dupilumab-treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis., Conclusions: Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab-treated patients require further study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD). In most dupilumab AD trials, dupilumab-treated patients had higher conjunctivitis incidence than those receiving placebo. Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare. Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add? This analysis confirms and extends the results of the individual clinical trials. Baseline disease-related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation-regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis. Patients who responded well to dupilumab had reduced incidence of conjunctivitis. Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab-treated patients with AD., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine., (© 2019 European Academy of Dermatology and Venereology.)

Background: Conjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab., Objective: To survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC)., Methods: Electronic survey and in-person discussion of management strategies., Results: Forty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist., Limitations: The study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey., Conclusion: The IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab., (© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: As novel systemic therapeutics for patients with atopic dermatitis (AD) are developed, ethical and methodological concerns regarding placebo-controlled-trials (PCT) have surfaced., Objective: To guide the design and implementation of PCT in AD, focusing on trials with systemic medications., Methods: A subgroup of the International Eczema Council (IEC) developed a consensus e-survey, which was disseminated to IEC members., Results: The response rate was 43/82 (52%). Consensus was reached on 24/27 statements and on 3/11 options from multiple-selection statements, including: performing monotherapy studies in proof-of-concept phases; avoiding concomitant topical corticosteroids or calcineurin inhibitors until a predefined timepoint as rescue (borderline consensus); selection of sites and assessors with recognized expertise in AD clinical trials; clear definition and identification of baseline disease severity; minimizing time and proportion of patients on placebo; using daily emollients with several options provided; instigating open-label extension studies for enrolment after a predefined timepoint; and including outcomes which set a higher bar for disease clearance., Conclusion: Conducting PCT in AD requires balancing several, sometimes opposing principles, including ethics, methodology, regulatory requirements and real-world needs. This paper can provide a framework for conducting PCT with systemic medications for patients with AD., (© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Atopic dermatitis is a chronic inflammatory skin disease that may require systemic therapy. Ciclosporin A (CsA) is a widely used, potent immunosuppressant but it is not effective in all patients with atopic dermatitis, and side-effects limit its use. Dupilumab, a fully human anti-interleukin 4 receptor-alpha monoclonal antibody, inhibits signaling of IL-4 and IL-13, key drivers of Type 2/Th2-mediated inflammation, and is approved in the U.S.A. and the European Union for the treatment of inadequately-controlled moderate-to-severe atopic dermatitis in adults., Objectives: To evaluate efficacy and safety of dupilumab with concomitant topical corticosteroids (TCS) in adults with atopic dermatitis with inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable., Methods: In this 16-week, double-blind, randomized, placebo-controlled, phase III trial, patients were randomized 1 : 1 : 1 to subcutaneous dupilumab 300 mg weekly (qw) or every 2 weeks (q2w) or placebo. All received concomitant medium-potency TCS from Week -2 through Week 16; dosage could be tapered if lesions cleared, or stopped for adverse reactions to TCS., Results: In total, 390 patients were screened, 325 were randomized, and 318 completed the trial. Treatment groups had similar baseline characteristics. Significantly more patients in the dupilumab qw + TCS and q2w + TCS groups achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index at Week 16 vs. the placebo + TCS group (primary end point) (59·1% and 62·6% vs. 29·6%, respectively; P < 0·001 vs. placebo + TCS, both doses). Other clinical outcomes and atopic dermatitis symptoms were significantly improved in the dupilumab qw + TCS and q2w + TCS groups, including pruritus, pain, sleep disturbance, symptoms of anxiety and depression, and quality of life (QoL). Treatment groups had similar overall rates of adverse events (qw + TCS, q2w + TCS and placebo + TCS groups: 69·1%, 72·0% and 69·4%, respectively) and serious adverse events (1·8%, 1·9% and 1·9%, respectively). Conjunctivitis was more frequent with dupilumab + TCS; skin infections were more frequent with placebo + TCS., Conclusions: Dupilumab + TCS significantly improved signs and symptoms of atopic dermatitis and QoL in adults with a history of inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. No new safety signals were identified., (© 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Preventing relapses of atopic dermatitis (AD) through the regular use of topical products to repair the skin barrier defect is an emerging concept. It is still unclear if some commonly used emollients exert a positive effect on the skin barrier., Objectives: To determine the skin barrier effects of emollients commonly prescribed in the U.K., Materials and Methods: Two cohorts of volunteers with quiescent AD undertook observer-blind forearm-controlled studies. The first cohort (18 volunteers) treated the volar side of one forearm with two fingertip units of Doublebase ™ gel twice daily for 4 weeks. The second cohort (19 volunteers) undertook the same regimen using Diprobase ® cream. Transepidermal water loss (TEWL), stratum corneum integrity and hydration, skin surface pH and redness were determined at the test sites before and after treatment., Results: Neither Diprobase ® cream nor Doublebase ™ gel significantly affected the underlying skin barrier function. Both emollients were associated with significantly increased skin surface pH immediately after application (by 0·8 ± 0·19 and 1·0 ± 0·18 units, respectively), and no erythema. Diprobase ® cream artificially and transiently (6 h) improved permeability barrier function by 2·9-3·1 g m -2  h -1 TEWL and increased skin hydration by 6·0-6·2 units. Doublebase ™ gel, containing humectants, was associated with a greater (between 10·1 and 13·0 units during the first 6 h) and more sustained increase in hydration, lasting more than 12 h following repeated use., Conclusions: Diprobase ® cream and Doublebase ™ gel are not associated with skin barrier harm and appear to be appropriate for AD treatment. While displaying emollient properties, neither formulation displayed an ability to actively improve sustained skin barrier function., (© 2016 British Association of Dermatologists.)

Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 yr old) and adults with mild-to-moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Atopic dermatitis (AD) is an inflammatory skin disease arising as a result of immune system and skin barrier defects. Topical corticosteroids are safe and effective treatments for AD, when used in short courses. Prolonged use is associated with skin barrier damage. Topical calcineurin inhibitors are alternative immune-modulating treatments for AD purported to have no negative effects on the skin barrier., Objectives: To compare the effects of betamethasone valerate 0·1% cream (BMVc) and tacrolimus 0·1% ointment (TACo) on the skin barrier., Methods: Twenty volunteers with quiescent AD (no active signs for 6 months) participated in a randomized observer-blind study, wherein BMVc was applied to one forearm and TACo to the other, twice daily for 4 weeks. The biophysical/biological properties of the stratum corneum were assessed before and after treatment. Nine volunteers with active disease and 10 with healthy skin were assessed at untreated sites., Results: BMVc significantly reduced skin barrier function, integrity and cohesion, and the levels of pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA) towards the subclinical barrier defect observed in patients with AD (nonlesional sites). TACo preserved skin barrier function, integrity, cohesion and PCA and UCA levels, while significantly increasing skin hydration to levels comparable with healthy skin. Both treatments reduced skin surface pH and trypsin-like protease activity, with TACo doing so to a significantly greater degree., Conclusion: In quiescent AD, 4 weeks of BMVc treatment adversely affected the biophysical properties of the skin and reduced the levels of natural moisturizing factor, whereas TACo improved the condition of the skin barrier., (© 2013 British Association of Dermatologists.)

The concept of disease modification has been introduced to define the therapeutic strategies aimed to break, stop, or reverse the natural course of a chronic invalidating disease. This strategy is tightly related to the biomarker-based stratification of affected patients using genetic and other biological markers. With regard to the progress in understanding the genetic background of atopic dermatitis (AD), its natural history and its pivotal role in the emergence of allergic asthma, the time is mature to foster the research field of biomarkers in AD and to consider the elaboration of disease-modifying strategies in the management of AD with the goal to stop or even reverse the atopic march., (© 2012 John Wiley & Sons A/S.)

Background: The emollient aqueous cream BP is frequently used for the treatment of atopic dermatitis (AD), yet it is associated with a high rate of adverse cutaneous reactions. It contains the harsh anionic surfactant sodium lauryl sulphate, a known negative environmental factor associated with the exacerbation of AD., Objectives: To investigate the effect of aqueous cream BP on stratum corneum (SC) integrity and skin barrier function in volunteers with a predisposition to a defective skin barrier., Methods: Thirteen volunteers with a previous history of AD (no symptoms for 6 months) applied aqueous cream BP twice daily to the volar side of one forearm for 4 weeks. The other forearm was left untreated as a control. Permeability barrier function and SC integrity were determined before and after treatment by measuring transepidermal water loss (TEWL) in conjunction with tape-stripping. For comparison, 13 volunteers with current AD were recruited for assessment, without treatment, of SC integrity and skin barrier function at unaffected sites., Results: Topical application of aqueous cream BP resulted in significant elevation of baseline TEWL and a concomitant decrease in SC integrity. Measurements made after no treatment in volunteers with current AD, at unaffected sites, suggest that application of aqueous cream BP negatively affects the skin barrier towards the damaged state associated with onset of flares of the disease., Conclusions: Aqueous cream BP used as a leave-on emollient caused severe damage to the skin barrier in volunteers with a previous history of AD. Aqueous cream BP should not be used as a leave-on emollient in patients with AD., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.)

Background: Topical pimecrolimus may maintain remissions of atopic dermatitis (AD) by inhibiting subclinical inflammation., Objective: To evaluate clinical and cytological effects of pimecrolimus in topical corticosteroid-treated and resolved AD lesions., Methods: Patients (n=67) with resolved AD lesions were randomized to 3-week double-blind treatment with either pimecrolimus cream 1% or vehicle cream. Outcome measures were reduction in Eczema Area and Severity Index (EASI) and number of leukocytes in skin biopsies in all randomized patients who were evaluable at the end of study., Results: The proportion of patients with a localized EASI<2 at the end of study was higher with pimecrolimus cream 1% than with vehicle cream (73.5 vs. 39.4%, respectively). There was a significant decrease in the number of infiltrating CD45+ cells in pimecrolimus cream 1% compared with placebo cream (-88.2 vs. 43.2 cells/mm(2), respectively, p=0.047) and a slight but nonsignificant reduction in the number of dermal dendritic cells, Langerhans cells, T cells and macrophages with pimecrolimus versus vehicle cream., Limitations: This was an exploratory study., Conclusion: Topical pimecrolimus was effective at maintaining betamethasone-17α-valerate-induced AD remission by inhibiting recurrences of the inflammatory infiltrate in the skin., (Copyright © 2010 S. Karger AG, Basel.)

Background: Cystatin A (CSTA) is a strong candidate for atopic dermatitis (AD) because it maps to AD susceptibility locus on chromosome 3q21 and it does inhibit Der p 1 and Der f 1, major house dust mite cysteine proteases and environmental triggers for AD and asthma., Objective: To examine any association between polymorphisms in CSTA and AD and study the effect on the CSTA mRNA expression level., Methods: We identified three polymorphisms and characterized the linkage disequilibrium mapping of the CSTA gene. All three CSTA polymorphisms were genotyped in 100 AD patients and 203 matched controls. Subsequently, we performed transfection-based RNA stability assays., Results: We found a significant association between the CSTA +344C variant and AD [odds ratio (OR) = 1.91; P = 0.024]. When further 61 control samples were genotyped. The association with CSTA +344C allele was enhanced OR = 2.13; P = 0.006. To test whether the CSTA +344 affected the CSTA transcriptional activity, the decay rates of RNAs transcribed from the CSTA +344C and CSTA +344T variants were investigated. COS-7 cells were transfected with a pcDNA3.1-CSTA+344C or a pcDNA3.1-CSTA+344T construct and cultured in the presence or absence of actinomycin D. Real-time RT-PCR revealed that CSTA +344C mRNA is more than two times less stable than the CSTA +344T mRNA (P < 0.001)., Conclusion: These results suggest that the CSTA +344C allele associated with unstable mRNA could result in failing to protect the skin barrier in AD patients from both exogenous and endogenous proteases.

Pimecrolimus is a calcineurin inhibitor developed for the topical treatment of atopic dermatitis. During the clinical development of 1% pimecrolimus cream, 1133 patients 3 to 23 months of age with mild to severe atopic dermatitis were treated for up to 2 years. The objective of this review is to discuss the safety and tolerability of 1% pimecrolimus cream among infants, on the basis of the combined results from all studies (4 pharmacokinetic studies and 6 clinical trials) conducted among these patients. Pimecrolimus blood concentrations measured for 35 patients were consistently low (< or =1 ng/mL in >80% of samples), irrespective of the disease severity and extent, and remained low during intermittent treatment for up to 1 year. The level of systemic exposure to pimecrolimus among infants was comparable to that observed for older pediatric patients enrolled in the same studies and treated in the same way with 1% pimecrolimus cream, which indicated that young pediatric patients are not at higher risk of significant percutaneous absorption of topically applied pimecrolimus, despite their large skin surface area/body mass ratio. The 6 clinical trials included a total of 1098 infants, who were treated for periods ranging from 4 weeks to 2 years. Most of these patients (60%) had moderate to severe disease at baseline. The most frequently reported adverse events were common childhood disorders such as nasopharyngitis, pyrexia, upper respiratory tract infections, ear infections, and bronchitis. During the double-blind (DB) studies or DB phases of studies, the incidence rates for the most frequently reported adverse events were similar for patients who received 1% pimecrolimus cream and patients who received the vehicle, except for the incidence of teething, which was higher among the pimecrolimus-treated infants (relative risk: 2.02; 95% confidence interval: 1.32-3.27). Treatment with 1% pimecrolimus cream was not associated with an increase in the overall incidence of nonskin infections, compared with the vehicle (relative risk: 1.015; 95% confidence interval: 0.88-1.18). The incidence density (ID) rates for total bacterial, fungal, parasitic, and viral skin infections during the DB studies or DB phases of studies were comparable for patients treated with 1% pimecrolimus cream and patients who received the vehicle. The ID rate of herpes simplex virus infections was 0.8 cases per 1000 patient-months of follow-up monitoring among patients treated with 1% pimecrolimus cream and 1.7 cases per 1000 patient-months of follow-up monitoring among patients who received the vehicle. Considering all 1098 infants treated with 1% pimecrolimus cream in DB trials and open-label studies, the ID rate of clinically diagnosed eczema herpeticum was 1.3 cases per 1000 patient-months of follow-up monitoring. Burning and erythema were the most frequently reported application site reactions, with ID rates of 2.0 and 1.2 cases per 1000 patient-months of follow-up monitoring, respectively. No sign of immunosuppression was found among infants treated intermittently with 1% pimecrolimus cream for up to 2 years; they demonstrated normal immune responses to vaccinations and did not show increases in the incidence of systemic infections or skin infections over time.

Background: Outcomes of health care interventions can be measured in many different ways, but there has been growing interest in the role that quality-adjusted life-years (QALYs) can play in informing priorities in health care. While existing generic preference-based measures can be used to obtain QALYs, these measures may often be inappropriate for some conditions such as atopic dermatitis (AD). These measures are also usually developed for adults and may not capture the domains pertinent to children., Objectives: To develop a preference-based quality-of-life measure for use in children with AD., Methods: Items generated from interviews conducted with parents of children with AD were used to form a health state classification system that gives 16 unique health states. One hundred and fifty members of the general population were interviewed to derive preference weights for these states, following the methods used in the valuation of the Health Utilities Index 2 (HUI 2). Each person valued 10 health states using the standard gamble technique. The primary analysis was the estimation of mean health state values for each of the 16 states., Results: Mean values across the 16 health states range from 0.36 (SD = 0.36) for the worst state to 0.84 (SD = 0.19) on a scale from zero to one, where zero is for health states thought to be as bad as being dead and one is for perfect health. There was some support for the validity of the values from the fact that the values were logically consistent with the ordering of the health state classification system., Conclusions: These results show the perceived importance of the defined health states of childhood AD to the general population. The resultant health state classification and values can be used to calculate QALYs for use in assessing the cost-effectiveness of interventions for children with AD.

Atopic dermatitis is a disease with an impaired skin barrier that affects 15%-20% of children. In the normal epidermis, the stratum corneum chymotryptic enzyme (SCCE) thought to play a central role in desquamation by cleaving proteins of the stratum corneum (e.g., corneodesmosin and plakoglobin). Genetic variations within the SCCE gene could be associated with dysregulation of SCCE activity leading to an abnormal skin barrier. We screened the SCCE gene for variations and performed a case-control study on 103 atopic dermatitis patients and 261 matched controls. 16 synonymous single nucleotide polymorphisms (SNPs) have been identified and a 4 bp (AACC) insertion has been found in the 3'UTR. We performed an association study of the SCCE AACC insertion in the 3'UTR, and found a significant trend between the AACC allele with the two insertions and disease in the overall data set [odds ratio (OR)=2.31; p=0.0007]. The AACC insertion in the SCCE gene may result in a change to SCCE activity within the skin barrier. These findings suggest that SCCE could have an important role in the development of atopic dermatitis.

Background: The failure of patients to take medicines in a way that leads to clinical benefit is a major challenge. A consensus has emerged that, on average, compliance sufficient to obtain therapeutic objectives occurs about half the time, with noncompliance contributing to therapeutic failure in the other half. These figures refer to simple oral regimens. There has been little work assessing compliance/concordance with complex treatment regimens for atopic eczema. Asthma schools led by specialist nurses have been shown to improve knowledge, use of therapies and clinical outcome., Objectives: To determine the effect of education and demonstration of topical therapies by specialist dermatology nurses on therapy utilization and severity of atopic eczema., Methods: Fifty-one children with atopic eczema attending a paediatric dermatology clinic were followed for up to 1 year. At each visit the parent's knowledge about atopic eczema and its treatment and therapy utilization was recorded. The severity of the eczema was recorded using the six area, six sign atopic dermatitis severity score (SASSAD) and parental assessment of itch, sleep disturbance and irritability. At the first visit a specialist dermatology nurse explained and demonstrated how to use all of the topical treatments. This education was repeated at subsequent visits depending on the knowledge of the parent., Results: At baseline less than 5% of parents had received/recalled receiving any explanation of the causes of eczema or demonstration of how to apply topical treatments. The eczema was poorly controlled in all children (mean SASSAD 42.9). Of the children, 24% were not being treated with any emollient cream/ointment; the mean use was 54 g weekly. Of the children, 25% were being inappropriately treated with potent or very potent topical steroids. Following repeated education and demonstration of topical therapies by a specialist dermatology nurse, there was an 89% reduction in the severity of the eczema. The main change in therapy utilization was an 800% increase in the use of emollients (to 426 g weekly of emollient cream/ointment) and no overall increase in the use of topical steroids, accounting for potency and quantity used., Conclusions: This study reinforces the importance of specialist dermatology nurses in the management of atopic eczema. It also confirms the opinion of patients, patient support groups, dermatologists and best practice guidelines that the most important intervention in the management of atopic eczema is to spend time to listen and explain its causes and demonstrate how to apply topical therapies.

Cyclosporin (CyA) has been shown to be highly effective and well tolerated in the short-term treatment of severe childhood atopic dermatitis; however, there is limited experience in its longer-term use. The aim of this study was to compare multiple short courses of CyA with continuous therapy for 1 year, with respect to efficacy, safety, tolerability and quality of life. Children aged 2-16 years, with a diagnosis of severe atopic dermatitis refractory to topical steroid therapy, were randomly assigned to receive short course therapy (multiple courses of 12 weeks) or continuous therapy. The starting dose and maximum dose for all patients was 5 mg/kg per day. Disease activity was monitored using the Six Area Six Sign Atopic Dermatitis score and the 'Rule of Nines' area score. Pruritus, sleep disturbance and irritability were measured using visual analogue scales, and topical therapy was monitored. Safety measurements included monitoring of serum creatinine, blood pressure and adverse events. Forty patients were included in the efficacy analysis, 21 of whom were randomized to the short course group (of whom six were withdrawn) and 19 to the continuous group (of whom five were withdrawn). Significant improvements were seen in all efficacy parameters at every time-point. There were no significant differences between groups, although the improvement was more consistent in the continuous arm. In the short course arm, 7 out of 21 patients could be managed by at least two short courses. The remaining 14 patients includes 12 who could not be controlled by at least two short courses, one patient who failed to return after week 12 and another patient who was withdrawn at week 4 due to an adverse event. Quality of life improved for both the children and their families. Tolerability was considered good or very good in at least 80% of the patients at week 12 and at the end of the study. No clinically significant change was seen in mean serum creatinine and no change was seen in mean blood pressure in either group. CyA is effective in controlling severe atopic dermatitis in children over a 1-year period and is well tolerated. More consistent control is achieved with continuous treatment; however, short course therapy was adequate for some patients, indicating that treatment should be tailored to the individual patient's needs. Short course treatment may produce prolonged remission in some cases and reduce the cumulative exposure to the drug.

Background: Severe atopic dermatitis (AD) remains difficult to treat. Cyclosporine is effective in adults but has not previously been investigated in children with AD., Objective: The aims were to investigate the efficacy, safety, and tolerability of cyclosporine in severe refractory childhood AD., Methods: Subjects 2 to 16 years of age were treated for 6 weeks with cyclosporine, 5 mg/kg per day, in an open study. Disease activity was monitored every 2 weeks by means of sign scores, visual analogue scales for symptoms, and quality-of-life questionnaires. Adverse events were monitored. Efficacy and tolerability were assessed with five-point scales., Results: Twenty-seven children were treated. Significant improvements were seen in all measures of disease activity. Twenty-two showed marked improvement or total clearing. Quality of life improved for both the children and their families. Tolerability was considered good or very good in 25 subjects., Conclusion: Cyclosporine may offer an effective, safe, and well-tolerated short-term treatment option for children with severe AD.