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Michael J Cork,1,2 Simon G Danby,1,2 Ana B Rossi,3 Ashish Bansal4 1Sheffield Dermatology Research, University of Sheffield, Sheffield, UK; 2Sheffield Children’s Hospital, Sheffield, UK; 3Sanofi, Cambridge, MA, USA; 4Regeneron Pharmaceuticals Inc., Tarrytown, NY, USACorrespondence: Michael J Cork, Sheffield Dermatology Research, Department of Infection and Immunity, The University of Sheffield, K Floor, The Medical School (RHH tower), Beech Hill, Sheffield, S10 2RX, UK, Email m.j.cork@sheffield.ac.ukAbstract: Atopic dermatitis (AD) is the most common inflammatory skin disease in children. Children with severe AD have a multidimensional disease burden characterized by skin lesions, itching, frequent infections, sleep deprivation, and a high rate of comorbidities. These impact the mental health and overall quality of life of not only the children but also of their parents and caregivers. There are few effective available treatment options for young children with severe AD that are suitable for long-term use. Due to their adverse effects, practice guidelines consider systemic agents inappropriate for this age group, although they are still used off-label in extreme cases. The biologic dupilumab has recently been approved for children aged 6– 11 years with severe (EU) and moderate-to-severe (USA) AD, offering hope to this population of patients with a high unmet clinical need. The purpose of this review is to describe the unmet needs of AD patients aged 6– 11 years prior to dupilumab approval and to summarize existing clinical data supporting dupilumab’s safety and efficacy in these children.Keywords: atopic dermatitis, children, dupilumab, pediatric, severe

BackgroundChildren 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.ObjectivesTo report the pharmacokinetic profile and long-term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD.MethodsChildren (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.ResultsOf 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.ConclusionsThese 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.

BackgroundDupilumab (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).ObjectivesTo characterize the pharmacokinetics of dupilumab, and long-term safety and efficacy in adolescents.MethodsThis 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).ResultsForty 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 )].ConclusionsIn 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.

BackgroundConjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab.ObjectiveTo 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).MethodsElectronic survey and in-person discussion of management strategies.ResultsForty-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.LimitationsThe study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey.ConclusionThe IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

Breakdown of the skin barrier is the first event in the development of atopic eczema (atopic dermatitis). Research over the past five years has indicated that this arises as a result of the interaction of environmental agents such as soap and other detergents with the products of changes in several genes. These genetic changes predispose to the breakdown of the skin barrier, which allows the penetration of allergens, triggering a flare of atopic eczema. This new understanding of how breakdown of the skin barrier is the first event in the development of atopic eczema provides a rationale for a renaissance in the use of a complete emollient therapy regimen in atopic eczema and related skin barrier breakdown diseases, such as asteatotic eczema and irritant contact dermatitis. [ABSTRACT FROM AUTHOR]

Topical steroid creams and ointments have been available as over-the-counter (OTC) medications for the self treatment of acute dermatitis and other steroid responsive skin disorders for more than ten years. Despite earlier fears, widespread availability and use of these creams is not associated with clinically significant adverse effects. In dermatological practice, hydrocortisone 1% remains the mainstay of treatment for facial eczema, but it is often not effective in eczema affecting other body areas. Eumovate™ (clobetasone butyrate 0.05%) cream has recently been made available as a pharmacy medication for the short-term management of acute eczema and allergic dermatitis by adults and children aged 10 or older, based on evidence derived from clinical trials involving over 3500 patients. This review summarises the key efficacy and safety data derived from 29 clinical trials and the postlicensing pharmacovigilance safety information, which supported the reclassification of this product for OTC use. These data show clobetasone butyrate 0.05% is more effective than 1.0% hydrocortisone in the treatment of eczema and more effective than fiurandrenolone 0.0125% (p=0.0l%) and a potent topical steroid hydrocortisone butyrate (p<0.05), in the treatment of psoriasis. A review of the effect of topical steroids on skin thickness concluded that, following short term application, there was no clinically significant difference between hydrocortisone 1.0% and clobetasone butyrate 0.05% in terms of potential for skin thinning. Similarly, even under extreme conditions, clobetasone butyrate 0.05% has negligible systemic absorption and has almost no effect on HPA axis function. [ABSTRACT FROM AUTHOR]

Background: Moderate-to-severe atopic dermatitis (AD) greatly impacts children/caregivers., Objective: Evaluate the impact of treatment with dupilumab on caregiver- and patient-reported AD symptoms and quality of life (QoL) in young children., Methods: In the LIBERTY AD PRESCHOOL (randomized, placebo-controlled) study, children aged 6 months to 5 years with moderate-to-severe AD received dupilumab or placebo plus low-potency topical corticosteroids for 16 weeks. This posthoc analysis assessed the change from baseline to week 16 in caregiver-reported outcome measures of AD symptoms (eg, itch and sleep) and QoL of patients and their caregivers/families., Results: Dupilumab (n = 83) vs placebo (n = 79) provided significant improvements in caregiver-reported AD symptoms and QoL. Significant improvements were seen as early as week 4 and sustained through the end of the study. Additionally, dupilumab vs placebo provided rapid and significant improvement in QoL measures for the patients' caregivers/families., Limitations: Few patients aged <2 years; significance only reported for prespecified endpoints; Infant's Dermatitis QoL Index severity strata adopted from Children's Dermatology Life Quality Index., Conclusion: Dupilumab improved AD symptoms and QoL in patients and their caregivers/families., Competing Interests: Conflicts of interest Dr Paller is a consultant for and has received honoraria from Aegerion Pharma, Azitra, BioCryst, Boehringer Ingelheim, Bristol Myers Squibb, Castle Creek Biosciences, Eli Lilly, Janssen, Krystal Biotech, LEO Pharma, Novartis, Regeneron Pharmaceuticals Inc, Sanofi, Seanergy, TWI Biotechnology, and UCB, is an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal Biotech, LEO Pharma, and UCB, and is on the data and safety monitoring boards of AbbVie, Abeona Therapeutics, Catawba Research, Galderma, and InMed Pharmaceuticals. Dr Silverberg has received honoraria as a consultant and/or advisory board member from AbbVie, Alamar Biosciences, Aldena Therapeutics, Amgen, AOBiome, Arcutis Biotherapeutics, Arena Pharmaceuticals, Asana BioSciences, Aslan Pharmaceuticals, BiomX, Biosion, Bodewell, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, Dermira, DermTech, Eli Lilly, Galderma, GSK, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, Menlo Therapeutics, Novartis, Optum, Pfizer, RAPT Therapeutics, Recludix Pharma, Regeneron Pharmaceuticals Inc, Sanofi, Shaperon, Target-RWE, UNION therapeutics, and UpToDate, has received speaker fees from AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron Pharmaceuticals Inc, and Sanofi, and institution grants from Galderma, Incyte, and Pfizer. Dr Simpson has received personal fees from AbbVie, Advances in Cosmetic and Medical Dermatology Hawaii, Amgen, AOBiome, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharmaceuticals, Boehringer Ingelheim, BMS, Boston Consulting Group, Collective Acumen, CorEvitas, Dermira, Eli Lilly, Evelo Biosciences, Evidera, Excerpta Medica, Forté Biosciences, Fraunhofer, Galderma, GSK, Incyte, Janssen, Johnson & Johnson, Kyowa Kirin, LEO Pharma, Medscape, Merck, Maui Derm, MJH Life Sciences, MLG Operating, Pfizer, Physicians World, PRImE, Regeneron Pharmaceuticals Inc, Revolutionizing Atopic Dermatitis, Roivant Sciences, Sanofi, Trevi Therapeutics, Valeant, Vindico Medical Education, and WebMD, and has received grants as a principal investigator from AbbVie, Amgen, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Castle Creek Biosciences, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Kirin, National Jewish Health, LEO Pharma, Pfizer, Regeneron Pharmaceuticals Inc, Sanofi, and Target RWE. Dr Cork is an investigator and/or consultant for AbbVie, Astellas Pharma, Boots, Dermavant, Galapagos, Galderma, Hyphens Pharma, Johnson & Johnson, LEO Pharma, L’Oréal, Menlo Therapeutics, Novartis, Oxagen, Pfizer, Procter & Gamble, Reckitt Benckiser, Regeneron Pharmaceuticals Inc, and Sanofi. Dr Arkwright is an investigator at Regeneron Pharmaceuticals Inc and LEO Pharma, and is a research grant advisor and lecturer with Sanofi. Dr Chen, Dr Bansal, and Dr Wang are employees/ shareholders of Regeneron Pharmaceuticals Inc. Dr Prescilla and Dr Marco are employees of Sanofi and may hold stock and/or stock options in the company. Dr Cork has no conflict of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Janus kinase inhibitors (JAKi) have the potential to alter the landscape of atopic dermatitis (AD) management dramatically, owing to promising efficacy results from phase III trials and their rapid onset of action. However, JAKi are not without risk, and their use is not appropriate for all patients with AD, making this a medication class that dermatologists should understand and consider when treating patients with moderate-to-severe AD., Objectives: To provide a consensus expert opinion statement from the International Eczema Council (IEC) that provides a pragmatic approach to prescribing JAKi, including choosing appropriate patients and dosing, clinical and laboratory monitoring and advice about long-term use., Methods: An international cohort of authors from the IEC with expertise in JAKi selected topics of interest were placed into authorship groups covering 10 subsections. The groups performed topic-specific literature reviews, consulted up-to-date adverse event (AE) data, referred to product labels and provided analysis and expert opinion. The manuscript guidance and recommendations were reviewed by all authors, as well as the IEC Research Committee., Results: We recommend that JAKi be considered for patients with moderate-to-severe AD seeking the benefits of a rapid reduction in disease burden and itch, oral administration and the potential for flexible dosing. Baseline risk factors should be assessed prior to prescribing JAKi, including increasing age, venous thromboembolisms, malignancy, cardiovascular health, kidney/liver function, pregnancy and lactation, and immunocompetence. Patients being considered for JAKi treatment should be current on vaccinations and we provide a generalized framework for laboratory monitoring, although clinicians should consult individual product labels for recommendations as there are variations among the different JAKi. Patients who achieve disease control should be maintained on the lowest possible dose, as many of the observed AEs occurred in a dose-dependent manner. Future studies are needed in patients with AD to assess the durability and safety of continuous long-term JAKi use, combination medication regimens and the effects of flexible, episodic treatment over time., Conclusions: The decision to initiate JAKi treatment should be shared between the patient and provider, accounting for AD severity and personal risk-benefit assessment, including consideration of baseline health risk factors, monitoring requirements and treatment costs., Competing Interests: Conflicts of interest A.A. has institutional grants with AbbVie, Almirall, Amgen, Arcutis, Bristol-Myers Squibb, Cara Therapeutics, Castle, Dermavant, Galderma, LEO Pharma, Novartis, Valeant (Bausch Health) and Vyne; is an advisory board member or consultant with Pfizer, AbbVie, Allergan, Almirall, Alphyn, Amgen, Apogee, Arcutis, Bausch Health, Beiersdorf, Bristol-Myers Squibb, Cara Therapeutics, Canfield, Castle, Cutera, Dermavant, Eli Lilly, EPI Health, Galderma, Incyte, Janssen, LEO Pharma, L’Oréal, Ortho, Sanofi Regeneron, Swiss-American, UCB, VisualDx and Vyne; and has given lectures and presentations for Pfizer, Bristol-Myers Squibb, Regeneron and Sanofi Genzyme. V.A. has clinical trials with Sanofi, Eli Lilly and Amgen, and has consulted for AbbVie and Pfizer. R.B. is an advisory board member, consultant, speaker and/or investigator for and receives honoraria and/or grants from AbbVie, Amgen, Apogee, Arcutis, Asana BioSciences, Bellus, BioMimetix, Bluefin, Biomedicine, Boehringer Ingelheim, Boston Pharma, CARA Therapeutic, Dermavant, Eli Lilly, Escient, Evidera, Fresh Tracks (Brickell), Galderma, GlaxoSmithKline, Incyte, Inmagene Bio, Janssen, LEO Pharma, Merck, Novartis, Opsidio, Pfizer, RAPT Therapeutic, Sanofi, Target RWE, Vyne Therapeutics and Zencor. R.B. is also an employee and shareholder of Innovaderm Research. A.B. has served as a speaker (received honoraria) for Eli Lilly, Pfizer and UCB; has served as a scientific adviser (received honoraria) for AbbVie, Abcentra, Aclaris, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Apogee, Arcutis, Arena, ASLAN, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, CTI BioPharma, Dermavant, EcoR1, Eli Lilly, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, LEO Pharma, Lipidio, Microbion, Merck, Monte Rosa Therapeutics, Nektar, Novartis, Overtone Therapeutics, Paragon, Pfizer, Q32 Bio, Rani, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, Takeda, TLL Pharmaceutical, TrialSpark, UCB Pharma, Union, Ventyx, Vibliome and Xencor; and has acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Concert, Dermavant, DermBiont, Eli Lilly, Evelo, Evommune, Galderma, Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, Takeda, UCB Pharma and Ventyx. R.C. has served as an advisor, consultant, speaker and/or investigator for AbbVie, Amgen, Apogee Therapeutics, Arcutis, Argenx, ASLAN Pharmaceuticals, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Dermavant, Eli Lilly, FIDE, Galderma, Genentech, GSK, Incyte, LEO Pharma, L’Oréal, Nektar Therapeutics, Opsidio, Pfizer, Regeneron, RAPT, Sanofi and UCB. M.J.C. has grants from Hyphens Pharma, Johnson & Johnson, Kymab, LEO Pharma, L’Oréal, Perrigo, Pfizer, Regeneron Pharmaceuticals and Sanofi; and has received personal fees from AbbVie, Astellas Pharma, Boots, Dermavant, Eli Lilly, Galapagos, Galderma, Hyphens Pharma, Johnson & Johnson, LEO Pharma, L’Oréal, Menlo Therapeutics, Novartis, Oxagen, Perrigo, Pfizer, Procter & Gamble, Reckitt Benckiser, Regeneron Pharmaceuticals and Sanofi. S.G.D. has grants with Sanofi, Almirall, Johnson & Johnson and LEO Pharma; and has received grants and personal fees from Perrigo, Pfizer and Hyphens Pharma. L.F.E. has served as a consultant, speaker, advisory board member or investigator for AbbVie, Amgen, Apogee, Arcutis, ASLAN, Bristol-Myers Squibb, Castle Biosciences, Dermavant, Eli Lilly, Forte, Galderma, Incyte, Janssen, Johnson & Johnson, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Target RWE and UCB. K.E. has served as a consultant and/or scientific advisor for AbbVie, Almirall, Bristol-Myers Squibb, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi and UCB; and has received research support from AbbVie, LEO Pharma, Lilly, Janssen and UCB. M.G. has served as an investigator, speaker and/or adviser for AbbVie, Amgen, Akros, Arcutis, Aristea, AnaptysBio, Apogee, Bausch Health, BMS, Boehringer Ingelheim, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Incyte, Janssen, Kyowa Kirin, LEO Pharma, Medimmune, Meiji, Merck, MoonLake, Nimbus, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Tarsus, Takeda, UCB, Union and Ventyx. E.G.-Y. has research grants from Boehringer Ingelheim, LEO Pharma, Pfizer, Cara Therapeutics, UCB, Kyowa Kirin, RAPT, Amgen, GSK, Incyte, Sanofi, Bristol-Meyers Squibb, ASLAN, Regeneron, AnaptysBio, Concert and Janssen; and has been a consultant for AbbVie, Almirall, Amgen, AnaptysBio, Apogee Therapeutics, Apollo Therapeutics, Artax Biopharma, AstraZeneca, Bristol-Meyers Squibb, Boehringer Ingelheim, Cara Therapeutics, Centrexion Therapeutics, Connect Biopharm, Eli Lilly, Enveda Biosciences, Escient Pharmaceuticals, Fairmount Funds Management, Galderma, Gate Bio, Google Ventures (GV), GSK Immunology, Horizon Therapeutics USA, Incyte, Inmagene, Janssen Biotech, Japan Tobacco, Jasper Therapeutics, Kyowa Kirin, LEO Pharma, Merck, Nektar Therapeutics, Novartis Pharmaceuticals, NUMAB Therapeutics, OrbiMed Advisors, OTSUKA Pfizer, Pharmaxis, Pioneering Medicine VII, Proteologix US, RAPT, Regeneron Pharmaceuticals, Ribon Therapeutics, Sanofi, SATO, Schrödinger, Sun Pharma Advanced Research Company (SPARC), Teva Branded Pharmaceutical Products R&D and UCB. D.-J.H. is or has been a consultant and/or investigator for AbbVie, Almirall, AstraZeneca, Galderma, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi and UCB. A.D.I. has received consulting fees from AbbVie, Almirall, Arena, Benevolent AI, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron and Sanofi; has patents pending with Johnson & Johnson and Regeneron; and is President Elect of the International Eczema Council. N.K. has received honoraria as a speaker/consultant for Sanofi, Maruho, AbbVie, Eli Lilly Japan, Taiho Pharmaceutical, Pfizer, Otsuka Pharmaceutical and LEO Pharma; and has received grants as an investigator from Maruho, Torii Pharmaceutical, AbbVie, Sun Pharma and LEO Pharma. Y.A.L. has received honoraria or fees as a consultant from AbbVie, Sanofi, Janssen, Pfizer, Eli Lilly and Genentech, and as an advisory board member from Sanofi, Regeneron Pharmaceuticals, Pfizer and AbbVie; has received an independent research grant from AbbVie; and has, without personal compensation, provided investigator services for Eli Lilly, Pfizer and AbbVie. D.F.M. has served as a consultant, investigator and/or on the advisory board for Sanofi, AbbVie, Arena, LEO Pharma, Eli Lilly, Galderma, Dermira, Pfizer, BMS, Kineska, Fujisawa, Novartis and Evelo. I.V. has received research support from Sanofi/Regeneron Pharmaceuticals, Pfizer, Eli Lilly, Almirall and AbbVie; personal honoraria for lecturing from Pfizer and AbbVie; and has been a subinvestigator for LEO Pharma. R.L.O. has been involved in clinical trials for Sanofi, Amgen and Lilly, and has been a consultant for AbbVie. A.S.P. has been an investigator for AbbVie, Applied Pharma Research, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, Regeneron and UCB; a consultant for Aegerion Pharma, Azitra, BioCryst, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, Johnson & Johnson, Krystal, LEO Pharma, Novartis, Primus, Regeneron, Sanofi Genzyme, Seanergy, TWI Biotechnology and UCB; and has been on data and safety monitoring boards for AbbVie, Abeona, Catawba, Galderma and InMed. D.R. has consulted, spoken for or conducted trials for the following companies: AbbVie, Abcuro, AltruBio, Amgen, Arena, Boehringer Ingelheim, Bristol-Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Galderma, Incyte, Janssen, Kyowa Kirin, Lilly, Merck, Nektar, Novartis, Pfizer, RAPT, Regeneron, Recludix, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, Viela Bio and Zura Bio. J.I.S. has received honoraria as a consultant and/or advisory board member for AbbVie, Aldena, Amgen, AOBiome, Apollo, Arcutis, Arena, Asana, ASLAN, Attovia, BiomX, Biosion, Bodewell, Boehringer Ingelheim, Bristol-Meyers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Invea, Kiniksa, LEO Pharma, My-Or Diagnostics, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi Genzyme, Shaperon, TARGET-RWE, Union and UpToDate; has been a speaker for AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron and Sanofi Genzyme; and their institution has received grants from Galderma, Incyte and Pfizer. E.L.S. reports personal fees from AbbVie, Amgen, Arcutis, Areteia Therapeutics, Bristol-Myers Squibb, CorEvitas, Corvus, Dermira, Eli Lilly, Evelo Biosciences, FIDE, Forte Bio RX, Galderma, GlaxoSmithKline, Gilead Sciences, Impetus Healthcare, Incyte, Innovaderm Reche, Janssen, Johnson & Johnson, Kyowa Kirin Pharmaceutical Development, LEO Pharma, Merck, MJH Holding, NUMAB Therapeutics, Pfizer, Physicians World, PRImE, Recludix Pharma, Regeneron, Roivant, Sanofi Genzyme, Trevi Therapeutics and Valeant; has received grants from (or serves as Principal investigator role for) AbbVie, Acrotech, Amgen, Arcutis, ASLAN, Castle, CorEvitas, Dermavant, Dermira, Incyte, Lilly, Kymab, Kyowa Kirin, National Jewish Health, LEO Pharma, Pfizer, Regeneron, Sanofi, Target and VeriSkin. S.S. has grants from Almirall, Beiersdorf, LEO Pharma, Galderma and Sanofi; has consulted for and been on advisory boards for AbbVie, Almirall, Beiersdorf, Clexio, Escient, Galderma, Grünenthal, Incyte, Integrity CE, Kiniksa, Klinge Pharma, Lilly, P.G. Unna Academy, Pfizer, Sanofi, touchIME, Vifor and WebMD; and has delivered lectures and presentations for AbbVie, BMS, FOMF, Galderma, LEO Pharma, L’Oréal, MEDahead, Moroscience, Novartis, Sanofi, P. G. Unna Academy, Pfizer, UCB and Vifor. J.P.T. reports, with no relation to the present manuscript, that he has previously been an advisor for AbbVie, Almirall, Arena Pharmaceuticals, OM Pharma, ASLAN Pharmaceuticals, Union Therapeutics, Eli Lilly, LEO Pharma, Pfizer, Regeneron and Sanofi Genzyme; has been a speaker for AbbVie, Almirall, Eli Lilly, LEO Pharma, Pfizer, Regeneron and Sanofi-Genzyme; and has received research grants from Pfizer, Regeneron and Sanofi Genzyme. He is currently an employee of LEO Pharma. J.Y. has served on advisory boards for Sanofi, Incyte and Arcutis; has served as a consultant for the National Eczema Association, iRhthym, O’Glacee and Inner Archways; and has served as site investigator on clinical trials sponsored by AbbVie, Pfizer, Lilly and SmartPractice. C.H., A.A.L., J.I.O., Y.R.-Y., N.S. and G.T. declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Attenuated total reflection (ATR) Fourier transform infrared spectroscopy (FT-IR) is used to characterize a vast array of materials at the molecular level in various industry types. Here we compare the performance of a portable spectrometer with a novel three-bounce-two-pass (3B2P) ATR scanning interface to the same device with a standard one-bounce (1B) ATR, and to a benchtop spectrometer with a 10-bounce (10B) ATR, in ideal sample-interface conditions and an applied dermatological study setting. In both application settings, the benchtop 10B ATR interface showed the highest signal-to-noise ratio (SNR), however, the novel 3B2P produced a six-fold increase in the sensitivity of the portable spectrometer when analyzing isopropanol and showed the greatest consistency of SNR of all devices when analyzing isopropanol and in vivo skin samples. Spectral data were sourced from a recently undertaken dermatological study involving a cohort of 180 healthy, full-term babies, using both 1B and 3B2P interfaces. Use of the 3B2P interface resulted in a 55% greater successful high-quality spectrum collection rate, compared to the 1B, and showed significantly superior SNR at both observed study time points, i.e., birth (1B: 68.37; 3B2P: 77.37), and at four weeks (1B: 74.53; 3B2P: 80.22). The utility of ATR FT-IR spectrometers as a dermatological clinical tool was also exemplified here, by quantifying the moisture level of newborn skin. By gathering rich spectroscopic data on the molecular structure of the skin, this technique holds great promise for the quantification of skin disease-specific biomarkers., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study aims to assess the efficacy and safety of combining the 308-nm Excimer lamp with Tacrolimus 0.1% ointment, compared to Tacrolimus 0.1% ointment monotherapy, for treating pediatric vitiligo involving less than 10% of the body surface area., Methods: Fifty pediatric patients with vitiligo were randomly assigned to two groups. Group A received Tacrolimus 0.1% ointment twice daily and Excimer light at 308-nm twice weekly, while Group B received Tacrolimus 0.1% ointment alone, administered twice daily. Repigmentation percentages were evaluated after 30, 90, and 180 days using the rule of nine., Results: Group A exhibited a significant improvement in repigmentation, increasing from 10% after one month to 65% after six months. In contrast, Group B observed an increase from 10% to 30% over the same timeframe. The efficacy of the treatment was significantly higher in Group A at both the 3-month and 6-month follow-up points ( p -value < .001). Moreover, Group A achieved notably higher repigmentation rates in the face, trunk, and lower limbs., Conclusion: The combination of Tacrolimus and the 308-nm excimer lamp yielded superior repigmentation results compared to Tacrolimus monotherapy in pediatric vitiligo patients. This combined approach may offer an effective new treatment protocol for pediatric vitiligo.

Background: The main conventional systemic treatments for atopic dermatitis (AD) are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomized controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA., Objectives: To compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD., Methods: We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). The minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression analysis was used to compare the hazard ratios of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits., Results: We included 488 patients (311 adults and 177 children/adolescents) on dupilumab (n = 282), MTX (n = 149) or CyA (n = 57). CyA and MTX were primarily used as the first-line treatment, while dupilumab was mainly a second-line systemic treatment as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared with MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared with MTX. In patients with severe disease the reduction in EASI, POEM and PP-NRS was even greater with CyA. The incidence rates of AEs were similar across groups (734, 654 and 594 per 10 000 person-month on CyA, dupilumab and MTX, respectively)., Conclusions: This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within 1 year of follow-up., Competing Interests: Conflicts of interest The full conflicts of interest statement is provided in Appendix 3., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Objective: To evaluate long-term infection rates in children aged 6 months to 5 years with moderate-to-severe atopic dermatitis (AD) treated with dupilumab., Methods: This was a post hoc analysis of an ongoing open-label extension (OLE) study of dupilumab. Pediatric patients aged 6 months to 5 years with moderate-to-severe AD who had previously taken part in the LIBERTY AD PRESCHOOL phase 2 and 3 clinical trials received weight-based subcutaneous dupilumab every 2 or 4 weeks. Exposure-adjusted infection rates after a median dupilumab exposure of 52 weeks are compared with data from the earlier randomized, placebo-controlled, 16-week LIBERTY AD PRESCHOOL phase 3 trial., Results: Infection rates were overall lower in the OLE study compared with the dupilumab and placebo groups in the earlier 16-week trial, including total infections (101.0 patients/100 patient-years [PY]), nonherpetic skin infections (22.7 patients/100PY), herpetic infections (7.3 patients/100PY), and nonskin infections (92.9 patients/100PY). The frequency of severe and serious infections was low (3.1 patients/100PY), compared with 17.1 placebo-treated patients/100PY and 0 dupilumab-treated patients in the earlier 16-week trial, and no infections leading to treatment discontinuation were observed. Systemic anti-infective medication use (58.9 patients/100PY) was lower in the OLE study compared with both the dupilumab and placebo groups in the 16-week trial., Conclusion: Overall, reduced infection rates are observed in infants and young children with moderate-to-severe AD treated with dupilumab long-term, supporting the known safety profile of dupilumab., (© 2024 Wiley Periodicals LLC.)

In a randomized phase 2b trial (NCT03703102) for adult patients with moderate-to-severe atopic dermatitis (AD), treatment with the T cell rebalancing anti-OX40 receptor antibody rocatinlimab (AMG 451/KHK4083) led to significant improvements in clinical measurements versus placebo including whole-body Eczema Area and Severity Index (EASI) score. AD manifestations can impact variable anatomic regions, and involvement of the head and neck, a sensitive, hard-to-treat area, can negatively impact quality of life. In this post hoc analysis, we investigated response to rocatinlimab treatment across anatomic regions, including the head and neck. Least squares mean change from baseline to Week 56 in EASI score was analyzed by anatomic region (head and neck, trunk, upper extremities, or lower extremities) for patients with baseline moderate-to-severe AD in the respective anatomic region, using mixed models for repeated measures. Rocatinlimab groups were compared with placebo at Week 16. The proportion of patients achieving at least 75% reduction from baseline in EASI (EASI-75) was calculated. Probability of relapsing in EASI-75 during the off-treatment follow-up period (Weeks 36-56) was estimated using a Kaplan - Meier approach. At Week 16, decrease from baseline in mean EASI score was greater with all rocatinlimab regimens versus placebo across all anatomic regions for patients with baseline moderate-to-severe AD in the respective region (all P < 0.001). EASI scores continued to improve on treatment after Week 16 and were maintained during the off-treatment period across all regions. Among patients with baseline moderate-to-severe AD in the head and neck (n = 219; rocatinlimab, n = 174; placebo, n = 45), mean difference (rocatinlimab vs placebo) at Week 16 in LS mean percent change in head and neck EASI score ranged from - 30.4% to - 42.6% across treatment regimens. In patients who received rocatinlimab from the start of the trial, 47% - 71% achieved EASI-75 in the head and neck at Week 36. Among EASI-75 responders at Week 36, the probability of relapsing in EASI-75 in any region was low (< 25% in the head and neck) 20 weeks after treatment discontinuation until Week 56.Rocatinlimab treatment led to durable improvements in AD across multiple anatomic regions, including the sensitive head and neck region., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest The full list of authors’ conflicts of interest is provided in Appendix S2 in the Supporting Information.

Interleukin-33 (IL-33) is a proinflammatory alarmin cytokine released by damaged epithelial tissue cells that initiates and amplifies both type 1 and type 2 inflammatory cascades. A role for IL-33 in atopic dermatitis (AD; a chronic, relapsing type 2 inflammatory disease of the skin) has been proposed. Itepekimab is a novel human IgG4P monoclonal antibody against IL-33, currently in clinical development for chronic obstructive pulmonary disease (COPD). Two global phase II studies-a dose-ranging itepekimab monotherapy study (NCT03738423) and a proof-of-concept study of itepekimab alone and in combination with dupilumab (NCT03736967)-were conducted in patients with moderate-to-severe AD to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy; both studies were terminated following an interim analysis of the proof-of-concept study, which failed to demonstrate the efficacy of itepekimab. In these two studies, itepekimab exhibited linear and dose-proportional pharmacokinetics. Pharmacodynamics of total IL-33 indicated that itepekimab saturated binding to the target in serum at 300 mg q2w and q4w doses, and decreased blood eosinophil counts. Concentration-time profiles of itepekimab and total IL-33 were similar for itepekimab with or without dupilumab, and between East Asian and non-East Asian subgroups. Itepekimab was generally well tolerated, both alone and in combination with dupilumab. The lack of clinical efficacy for itepekimab observed in these studies suggests that IL-33 may not be a key pathogenic driver in moderate-to-severe AD., (© 2024 Regeneron Pharmaceuticals Inc and The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Abrocitinib, an oral, once-daily, Janus kinase (JAK) 1-selective inhibitor, is approved for the treatment of adults and adolescents with moderate-to-severe atopic dermatitis (AD). Abrocitinib has shown rapid and sustained efficacy in phase 3 trials and a consistent, manageable safety profile in long-term studies. Rapid itch relief and skin clearance are more likely to be achieved with a 200-mg daily dose of abrocitinib than with dupilumab. All oral JAK inhibitors are associated with adverse events of special interest and laboratory changes, and initial risk assessment and follow-up monitoring are important. Appropriate selection of patients and adequate monitoring are key for the safe use of JAK inhibitors. Here, we review the practical use of abrocitinib and discuss characteristics of patients who are candidates for abrocitinib therapy. In general, abrocitinib may be used in all appropriate patients with moderate-to-severe AD in need of systemic therapy, provided there are no contraindications, e.g., in patients with active serious systemic infections and those with severe hepatic impairment, as well as pregnant or breastfeeding women. For patients aged ≥ 65 years, current long-time or past long-time smokers, and those with risk factors for venous thromboembolism, major adverse cardiovascular events, or malignancies, a meticulous benefit-risk assessment is recommended, and it is advised to start with the 100-mg dose, when abrocitinib is the selected treatment option., (© 2024. The Author(s).)

Background: Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management., Objectives: The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE., Methods: In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg)., Results: Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0-5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator's Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores., Conclusions: Consistent with results seen in adults, adolescents, and older children (aged 6-11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population., Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B)., (© 2024. The Author(s).)

Background: Atopic eczema is a common childhood skin problem linked with asthma, food allergy and allergic rhinitis that impairs quality of life., Objectives: To determine whether advising parents to apply daily emollients in the first year can prevent eczema and/or other atopic diseases in high-risk children., Design: A United Kingdom, multicentre, pragmatic, two-arm, parallel-group randomised controlled prevention trial with follow-up to 5 years., Setting: Twelve secondary and four primary care centres., Participants: Healthy infants (at least 37 weeks' gestation) at high risk of developing eczema, screened and consented during the third trimester or post delivery., Interventions: Infants were randomised (1 : 1) within 21 days of birth to apply emollient (Doublebase Gel®; Dermal Laboratories Ltd, Hitchin, UK or Diprobase Cream®) daily to the whole body (excluding scalp) for the first year, plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). Families were not blinded to allocation., Main Outcome Measures: Primary outcome was eczema diagnosis in the last year at age 2 years, as defined by the UK Working Party refinement of the Hanifin and Rajka diagnostic criteria, assessed by research nurses blinded to allocation. Secondary outcomes up to age 2 years included other eczema definitions, time to onset and severity of eczema, allergic rhinitis, wheezing, allergic sensitisation, food allergy, safety (skin infections and slippages) and cost-effectiveness., Results: One thousand three hundred and ninety-four newborns were randomised between November 2014 and November 2016; 693 emollient and 701 control. Adherence in the emollient group was 88% (466/532), 82% (427/519) and 74% (375/506) at 3, 6 and 12 months. At 2 years, eczema was present in 139/598 (23%) in the emollient group and 150/612 (25%) in controls (adjusted relative risk 0.95, 95% confidence interval 0.78 to 1.16; p = 0.61 and adjusted risk difference -1.2%, 95% confidence interval -5.9% to 3.6%). Other eczema definitions supported the primary analysis. Food allergy (milk, egg, peanut) was present in 41/547 (7.5%) in the emollient group versus 29/568 (5.1%) in controls (adjusted relative risk 1.47, 95% confidence interval 0.93 to 2.33). Mean number of skin infections per child in the first year was 0.23 (standard deviation 0.68) in the emollient group versus 0.15 (standard deviation 0.46) in controls; adjusted incidence rate ratio 1.55, 95% confidence interval 1.15 to 2.09. The adjusted incremental cost per percentage decrease in risk of eczema at 2 years was £5337 (£7281 unadjusted). No difference between the groups in eczema or other atopic diseases was observed during follow-up to age 5 years via parental questionnaires., Limitations: Two emollient types were used which could have had different effects. The median time for starting emollients was 11 days after birth. Some contamination occurred in the control group (< 20%). Participating families were unblinded and reported on some outcomes., Conclusions: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children. Emollient use was associated with a higher risk of skin infections and a possible increase in food allergy. Emollient use is unlikely to be considered cost-effective in this context., Future Research: To pool similar studies in an individual patient data meta-analysis., Trial Registration: This trial is registered as ISRCTN21528841., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/67/12) and is published in full in Health Technology Assessment ; Vol. 28, No. 29. See the NIHR Funding and Awards website for further award information.

Background: Atopic dermatitis (AD) is characterized by skin barrier defects that are often measured by biophysical tools that observe the functional properties of the stratum corneum (SC)., Objectives: To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in the chemical composition of the SC in relation to AD severity., Methods: We conducted an observational cross-sectional cohort study where attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL), combined with tape stripping, in a cohort of 75 participants (55 patients with AD stratified by phenotypic severity and 20 healthy controls). Common FLG variant alleles were genotyped., Results: Reduced hydration, elevated TEWL and redness were all associated with greater AD severity. Spectral analysis showed a reduction in 1465 cm-1 (full width half maximum) and 1340 cm-1 peak areas, indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups, which correlated with clinical severity (lipid structure r = -0.59, carboxylate peak area r = -0.50)., Conclusions: ATR-FTIR spectroscopy is a suitable tool for the characterization of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatment based on chemical structural deficiencies., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: A diagnosis of atopic dermatitis (AD) is common during infancy; however, it is unclear whether differential skin barrier development defines this period and signals disease onset in predisposed individuals., Objective: We sought to study (NCT03143504) and assess the feasibility of remote skin testing from birth to monitor skin barrier maturation and model association with an AD diagnosis by age 12 months., Methods: Biophysical testing and infrared spectroscopy were conducted at the maternity ward and family home. Tape stripping collected samples for desquamatory protease and natural moisturizing factor analysis. The 4 common European filaggrin risk alleles were screened., Results: A total of 128 infants completed the study, with 20% developing mild disease. Significant changes in permeability barrier function, desquamatory protease activity, and molecular composition assessed spectroscopically were observed longitudinally, but only subtle evidence of differential skin barrier development was noted between infant subgroups. Common filaggrin risk alleles were strongly associated with early-onset disease and conferred a significant reduction in natural moisturizing factor and water content by age 4 weeks. Accounting for a family history of atopy, these parameters alongside a greater lipid/protein ratio and reduced chymotrypsin-like activity at birth were associated with AD. Measured in ambient conditions, transepidermal water loss did not signal disease risk at any stage., Conclusions: Skin barrier dysfunction lacked an acquired modality but was considered proportional to cohort severity and suggests that a portfolio of tests used in a community setting has the potential to improve current AD risk evaluations from birth., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with atopic dermatitis (AD), particularly infants and young children, are at greater risk of developing skin infections. In this study, we assessed infection rates in AD patients aged 6 months to 5 years treated with dupilumab., Methods: In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo, with concomitant low-potency topical corticosteroids, every 4 weeks for 16 weeks. Exposure-adjusted infection rates were used to compare treatment groups., Results: The analysis included 162 patients, of whom 83 received dupilumab and 79 received placebo. Total infection rates were not significantly different between the dupilumab and placebo groups (rate ratio [RR] 0.75, 95% CI 0.48-1.19; p = 0.223). Non-herpetic adjudicated skin infections and bacterial infections were significantly less frequent with dupilumab versus placebo (non-herpetic skin infections: RR 0.46, 95% CI 0.21-0.99; p = 0.047; bacterial infections: RR 0.09, 95% CI 0.01-0.67; p = 0.019), and the number of patients using systemic anti-infective medication was significantly lower in the dupilumab group (RR 0.52, 95% CI 0.30-0.89; p = 0.019). There were no significant differences in the number of herpetic infections between the dupilumab and placebo groups (RR 1.17, 95% CI 0.31-4.35; p = 0.817). The number of patients with two or more infection events was significantly higher in the placebo group (RR 0.29, 95% CI 0.12-0.68; p = 0.004), and no severe or serious infections (including eczema herpeticum) were observed among patients receiving dupilumab., Conclusions: These data suggest that dupilumab treatment in infants and children younger than 6 years with AD does not increase overall risk of infections and is associated with a reduced risk of bacterial and non-herpetic skin infections compared with placebo, resulting in a reduced need for anti-infective medication., Trial Registration: The trial was registered with ClinicalTrials.gov with ID number NCT03346434 on November 17, 2017. INFOGRAPHIC., (© 2024. The Author(s).)

In young children, atopic dermatitis (AD) imposes a multidimensional burden on many aspects of their quality of life (QoL) and that of their families. LIBERTY AD PRESCHOOL part B was a randomized, double- blinded, placebo-controlled phase 3 trial in 162 children (aged 6 months to 5 years) with moderate-to- severe AD receiving dupilumab or placebo, plus low-potency topical corticosteroids. Post hoc analyses were performed on the full analysis set (FAS) and a subset of patients with Investigator's Global Assessment score > 1 at week 16. The primary outcome was the proportion of patients at week 16 achieving a composite endpoint encompassing clinically meaningful changes in AD signs, symptoms and QoL: ≥ 50% improvement in Eczema Area and Severity Index; and/or ≥ 4-point reduction in worst scratch/itch numerical rating scale; and/or ≥ 6-point reduction in Children's Dermatology Life Quality Index/Infants' Dermatitis Quality of Life Index. Significantly more patients receiving dupilumab vs placebo achieved the composite endpoint in both the FAS (77.7% vs 24.6%, p < 0.0001) and subgroup (68.9% vs 21.5%, p < 0.0001). Dupilumab provided rapid and significant, clinically meaningful improvements in AD signs, symptoms, and QoL in the overall group and subgroup of patients who did not achieve clear or almost clear skin at week 16.

Introduction: The skin of patients with atopic dermatitis (AD) is characterised by elevated pH. As a central homeostatic regulator, an increased pH accelerates desquamation and suppresses lipid processing, resulting in diminished skin barrier function. The aim of this study was to determine whether a novel zinc lactobionate emollient cream can strengthen the skin barrier by lowering skin surface pH., Methods: A double-blind, forearm-controlled cohort study was undertaken in patients with AD. Participants applied the test cream to one forearm and a vehicle cream to the other (randomised allocation) twice daily for 56 days. Skin surface pH and barrier function (primary outcomes) were assessed at baseline and after 28 days and 56 days of treatment, amongst other tests., Results: A total of 23 adults with AD completed the study. During and after treatment, a sustained difference in skin surface pH was observed between areas treated with the test cream and vehicle (4.50 ± 0.38 versus 5.25 ± 0.54, respectively, p < 0.0001). This was associated with significantly reduced transepidermal water loss (TEWL) on the test cream treated areas compared with control (9.71 ± 2.47 versus 11.20 ± 3.62 g/m 2 /h, p = 0.0005). Improvements in skin barrier integrity, skin sensitivity to sodium lauryl sulphate, skin hydration, and chymotrypsin-like protease activity were all observed at sites treated with the test cream compared with the control., Conclusion: Maintenance of an acidic skin surface pH and delivery of physiologic lipids are beneficial for skin health and may help improve AD control by reducing sensitivity to irritants and allergens., (© 2024. The Author(s).)

Background and Objective: Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) is a difficult endpoint to achieve after short-term treatment of chronic moderate-to-severe atopic dermatitis, and does not fully reflect clinically meaningful changes in other parameters. We assessed the impact of tralokinumab versus placebo on other clinically meaningful parameters in patients not achieving IGA 0/1 at week 16 using pooled data from two monotherapy phase III trials, ECZTRA 1 and 2., Methods: This post hoc analysis included patients (n = 1328) from ECZTRA 1 and 2 who did not achieve the co-primary endpoint, IGA 0/1 at week 16 without rescue medication. Endpoints evaluating atopic dermatitis extent and severity included proportions of patients achieving IGA 0/1, 50%, 75%, and 90% improvement in Eczema Area and Severity Index (EASI-50/75/90); endpoints evaluating patient-reported outcomes included a ≥ 3-point improvement in worst daily pruritus Numerical Rating Scale (NRS), a ≥ 3-point improvement in eczema-related sleep interference (sleep) NRS, a ≥ 4-point improvement in Dermatology Life Quality Index (DLQI), and DLQI ≤ 5. Specifically, clinically meaningful responses were defined as EASI-50, a ≥ 3-point improvement in itch NRS, or a ≥ 4-point improvement in DLQI at week 16., Results: Among ECZTRA 1 and 2 patients who did not achieve IGA 0/1 at week 16 without rescue medication, a significantly greater proportion of patients receiving tralokinumab versus placebo achieved EASI-50 (33.0% vs 13.0%), a ≥ 3-point improvement in itch NRS (22.6% vs 9.4%), or a ≥ 4-point improvement in DLQI (41.2% vs 24.5%) at week 16. In addition, compared with placebo, a numerically greater proportion of tralokinumab-treated patients achieved all three measures of clinically meaningful response (30% vs 18%) or a clinically meaningful change in at least one outcome (48.8% vs 28.5%). Significantly greater proportions of patients receiving tralokinumab versus placebo achieved additional clinician-reported and patient-reported outcomes, such as EASI-75 (13.5% vs 4.1%), EASI-90 (3.5% vs 1.1%), DLQI ≤ 5 (22.5% vs 12.5%), and a ≥ 3-point improvement in sleep NRS (24.5% vs 11.5%)., Conclusions: Tralokinumab provided clinically meaningful responses in patients with moderate-to-severe atopic dermatitis who did not achieve IGA 0/1 at week 16 and/or used rescue medication. Using multiple validated outcome measures of both efficacy and quality of life, alongside IGA scores, can better characterize tralokinumab treatment responses in patients with moderate-to-severe atopic dermatitis. [Video abstract available] CLINICAL TRIAL REGISTRATION: NCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study completion date: 10 October, 2019. NCT03160885 (ECZTRA 2); study start date: 12 June, 2017; primary completion date: 4 September, 2019; study completion date: 14 August, 2019. Video abstract: Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1 (MP4 362818 KB)., (© 2023. The Author(s).)

Background: Differences in atopic dermatitis (AD) disease course and manifestation with age may extend to treatment response., Objective: To evaluate response maintenance with continuous-/reduced-dose abrocitinib or withdrawal and response to treatment reintroduction after flare in adolescent and adult participants in JADE REGIMEN (NCT03627767)., Methods: Adolescents (12-17 years) and adults with moderate-to-severe AD responding to abrocitinib 200-mg induction were randomly assigned to 40-week maintenance with abrocitinib (200 mg/100 mg) or placebo. Patients who experienced flare during maintenance received rescue treatment., Results: Of 246 adolescents and 981 adults, 145/246 (58.9%) and 655/981 (66.8%), respectively, responded to induction. Similar proportions of adolescents and adults experienced flare during maintenance with abrocitinib 200 mg (14.9%/16.9%), 100 mg (42.9%/38.9%), and placebo (75.5%/78.0%). From the abrocitinib 200-mg, 100-mg, and placebo arms, respectively, Eczema Area and Severity Index response was recaptured by 28.6%, 25.0%, and 52.9% of adolescents and 34.3%, 33.7%, and 58.0% of adults; Investigator's Global Assessment response, by 42.9%, 50.0%, and 73.5% of adolescents and 34.3%, 50.6%, and 74.1% of adults. Abrocitinib had a similar safety profile regardless of age; nausea incidence was higher in adolescents., Limitations: Adolescents represented 20% of the trial population., Conclusion: Abrocitinib was effective in preventing flare in adolescents and adults.Clinicaltrials.gov listing: NCT03627767.

Background: Conventional systemic drugs are used to treat children and young people (CYP) with severe atopic dermatitis (AD) worldwide, but no robust randomized controlled trial (RCT) evidence exists regarding their efficacy and safety in this population. While novel therapies have expanded therapeutic options, their high cost means traditional agents remain important, especially in lower-resource settings., Objectives: To compare the safety and efficacy of ciclosporin (CyA) with methotrexate (MTX) in CYP with severe AD in the TREatment of severe Atopic Eczema Trial (TREAT) trial., Methods: We conducted a parallel group assessor-blinded RCT in 13 UK and Irish centres. Eligible participants aged 2-16 years and unresponsive to potent topical treatment were randomized to either oral CyA (4 mg kg-1 daily) or MTX (0.4 mg kg-1 weekly) for 36 weeks and followed-up for 24 weeks. Co-primary outcomes were change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare (relapse) after treatment cessation. Secondary outcomes included change in quality of life (QoL) from baseline to 60 weeks; number of participant-reported flares following treatment cessation; proportion of participants achieving ≥ 50% improvement in Eczema Area and Severity Index (EASI 50) and ≥ 75% improvement in EASI (EASI 75); and stratification of outcomes by filaggrin status., Results: In total, 103 participants were randomized (May 2016-February 2019): 52 to CyA and 51 to MTX. CyA showed greater improvement in disease severity by 12 weeks [mean difference in o-SCORAD -5.69, 97.5% confidence interval (CI) -10.81 to -0.57 (P = 0.01)]. More participants achieved ≥ 50% improvement in o-SCORAD (o-SCORAD 50) at 12 weeks in the CyA arm vs. the MTX arm [odds ratio (OR) 2.60, 95% CI 1.23-5.49; P = 0.01]. By 60 weeks MTX was superior (OR 0.33, 95% CI 0.13-0.85; P = 0.02), a trend also seen for ≥ 75% improvement in o-SCORAD (o-SCORAD 75), EASI 50 and EASI 75. Participant-reported flares post-treatment were higher in the CyA arm (OR 3.22, 95% CI 0.42-6.01; P = 0.02). QoL improved with both treatments and was sustained after treatment cessation. Filaggrin status did not affect outcomes. The frequency of adverse events (AEs) was comparable between both treatments. Five (10%) participants on CyA and seven (14%) on MTX experienced a serious AE., Conclusions: Both CyA and MTX proved effective in CYP with severe AD over 36 weeks. Participants who received CyA showed a more rapid response to treatment, while MTX induced more sustained disease control after discontinuation., Competing Interests: Conflicts of interest C.F. is Chief Investigator of the UK National Institute for Health Research-funded TREAT (ISRCTN15837754) and SOFTER (ClinicalTrials.gov: NCT03270566) trials, as well as the UK–Irish Atopic eczema Systemic Therapy Register (A-STAR; ISRCTN11210918) and a Principal Investigator in the European Union (EU) Horizon 2020-funded BIOMAP Consortium (http://www.biomap-imi.eu). He also leads the EU Trans-Foods consortium. His department has received investigator-led funding from Sanofi-Genzyme and Pfizer for microbiome work. D.O’K. has received funding for advisory board participation with Sanofi-Genzyme. M.W. is a steering committee member of A-STAR (ISRCTN11210918). T.M. has received funding for advisory boards and teaching from Sanofi-Genzyme, AbbVie and Pfizer. M.J.C. has received investigator-led funding from Hyphens Pharma, Johnson & Johnson, Sanofi, L’Oréal, LEO Pharma, ACO Nordic, Pfizer, Regeneron and Sanofi-Genzyme, as well as funding for advisory board participation with Menlo. He has also received consultant fees from Boots, Eli Lilly and Procter & Gamble. S.J.B. is a medical advisor to the Ichthyosis Support Group and Eczema Outreach Support and has received funding from the Wellcome Trust. A.D.I. has received consulting fees from Area, Almirall, AbbVie, Pfizer, Eli Lilly and Sanofi-Regeneron, and is the Director of the International Eczema Council. A.R.-H., A.P.J., B.R.T., C.S., M.-L.L., E. Hilger, M.D.S., F.A., F.B., D.G., P.B., B.E., J.E.G., S.A., S.B., P.R.W., L.S.T., R.H., T.H.S., E. Howard, J.R. and L.S. declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: For children aged 6-11 years with uncontrolled severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo with an acceptable safety profile. However, longer-term safety and efficacy data are important to inform longitudinal AD management., Objectives: This analysis of data from an open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in children with severe AD who had participated in the pivotal dupilumab LIBERTY AD PEDS study (NCT03345914)., Methods: Enrolled patients initially received subcutaneous dupilumab 300 mg every 4 weeks (q4w). The q4w regimen could be uptitrated to dupilumab dose regimens of 200 or 300 mg every 2 weeks (q2w; for body weight < 60 or ≥ 60 kg, respectively) for patients who did not achieve an Investigator's Global Assessment (IGA) score of 0/1 (clear/almost clear skin) at week 16, or prior to week 16 as rescue treatment. Additional patients were uptitrated to a weight-tiered q2w regimen following a protocol amendment. Patients who maintained an IGA score of 0/1 continuously for a 12-week period after week 40 discontinued dupilumab. They were monitored for relapse and were reinitiated on dupilumab if required., Results: Data for 321 patients (mean age 8.6 years) were analyzed, 254 (79%) of whom had completed the scheduled 52-week visit at the database lock. Most treatment-emergent adverse events were mild/moderate. By week 52, 41% of patients achieved an IGA score of 0/1, and 97%, 82%, and 50%, respectively, had at least a 50%, 75%, and 90% improvement from the parent study baseline in Eczema Area and Severity Index (EASI). By week 52, 29% of patients in the overall population had clear/almost clear skin sustained for 12 weeks and had stopped medication; of these, 40% relapsed and were subsequently reinitiated on treatment, with a mean time to reinitiation of 13.5 (standard deviation 5.2) weeks. Following reinitiation of dupilumab, 41% of the patients with evaluable data at the time of database lock had regained an IGA 0/1 clinical response., Conclusions: Consistent with results seen in adults and adolescents, long-term treatment with dupilumab in children aged 6-11 years with severe AD showed an acceptable safety profile and incremental clinical benefit. A substantial proportion of children who stopped dupilumab treatment after achieving clear/almost clear skin subsequently experienced disease recurrence, and required reinitiation of dupilumab, suggesting that continuous treatment may be necessary for maintenance of clinical benefit., Trial Registration: ClinicalTrials.gov Identifier NCT02612454., (© 2023. The Author(s).)

Background: Atopic dermatitis (AD) is an inflammatory skin disease with significant unmet need. Blockade of the OX40-OX40 ligand (OX40L) costimulation pathway by targeting OX40L on antigen-presenting cells (APCs) with a fully human noncytotoxic, nondepleting anti-OX40L monoclonal antibody (amlitelimab; SAR445229; KY1005) is a novel way to modulate persistent inflammation., Objectives: To assess the safety and efficacy of amlitelimab over 16 weeks in adults with AD in a phase IIa double-blind placebo-controlled study., Methods: The study was conducted at 19 hospitals in Germany, Poland, Spain and the UK. Eligible patients with moderate-to-severe AD were randomized (1 : 1 : 1) to low-dose intravenous (IV) amlitelimab (200 mg), high-dose IV amlitelimab (500 mg) or placebo, followed by three maintenance doses (50% of loading dose) at 4, 8 and 12 weeks, with safety follow-up to week 36. The co-primary endpoints were the incidence of treatment-emergent adverse events (all patients who received ≥ 1 dose of the study drug) and mean percentage change in Eczema Area and Severity Index (EASI) to week 16 (full analysis set)., Results: Between 13 December 2018 and 12 May 2020, 89 patients were randomly assigned to low- (n = 29) or high-dose amlitelimab (n = 30) or placebo (n = 29), of whom 88 proceeded to treatment [37 women (42%), 51 (58%) men; mean (SD) age 33.6 (11.9) years]. Amlitelimab was generally well tolerated with an unremarkable safety profile; no hypersensitivity events were reported. For the primary endpoint, the least square mean percentage change in EASI from baseline to week 16 was -80.12% [95% confidence interval (CI) -95.55 to -64.68; P = 0.009 vs. placebo] and -69.97% (95% CI -85.04 to -54.60; P = 0.07 vs. placebo) for the low- (n = 27) and high-dose (n = 27) amlitelimab groups, respectively, vs. -49.37% (95% CI -66.02 to -32.72) for placebo (n = 24). Numerically greater reductions in EASI were observed for amlitelimab vs. placebo from weeks 2 to 16., Conclusions: Novel targeting of OX40L-expressing APCs with amlitelimab was well tolerated and resulted in clinically meaningful improvements in AD., Competing Interests: Conflicts of interest: S.W. reports research grants (institutional) from AbbVie, Almirall, Eli Lilly, Galderma, LEO Pharma, Pfizer and Sanofi; and consultancy fees from AbbVie, Almirall, Boehringer, Eli Lilly, Galderma, LEO Pharma, Pfizer and Sanofi. T.B. reports consultancy fees from AbbVie, Affibody, Almirall, AnaptysBio, Asana Biosciences, ASLAN Pharmaceuticals, Bayer Health, BioVerSys, Boehringer Ingelheim, Bristol-Myers Squibb, Connect Pharma, Dermavant, DIECE Therapeutics, Domain Therapeutics, EQRx, Galderma, Glenmark, GSK, Incyte, Innovaderm, IQVIA, Janssen, Kirin, Kymab, LEO, LG Chem, Lilly, L’Oréal, MSD, Novartis, Numab, OM-Pharma, Pfizer, Pierre Fabre, Sanofi/Regeneron and UCB. M.J.C. reports research grants (institutional) and consultancy fees from Hyphens Pharma, Johnson & Johnson, Kymab, L’Oréal, Leo Pharma, Perrigo (ACO Nordic), Pfizer, Regeneron and Sanofi Genzyme; and is a board member of the European Academy of Dermatology and Venereology and a voluntary medical advisor to the National Eczema Society, UK. A.R. reports research grants (personal and institutional) from AbbVie, Alvotech, Amgen, AnaptysBio, Argenx, AstraZeneca, Biothera, BMS, Celgene, Celltrion, Dermira, Galderma, Inflarx, Janssen, Kiniksa, Kymab, Leo Pharma, Novartis, Pfizer, Trevi Therapeutics and UCB; and consultancy fees from AbbVie, Chema Rzeszow, Eli Lilly, Galderma, Leo Pharma, Novartis, Sandoz, Sanofi-Aventis and Takeda. B.P.-B. was an employee of Sanofi and Sanofi stockholder during the development of this manuscript. N.B. is a former employee and shareholder in Kymab Ltd. S.G. is a former employee of Kymab Ltd and a Sanofi stockholder. S.Q. is a former employee of Kymab Ltd. M.S. is a former employee of Sanofi. R.W. has received consultancy fees from Kymab Ltd. J.T.O’M. is an employee of Sanofi and may hold stock and/or stock options in the company., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Recent discoveries have led to the suggestion that enhancing skin barrier from birth might prevent eczema and food allergy., Objective: To determine the cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children at 2 years from a health service perspective. We also considered a 5-year time horizon as a sensitivity analysis., Methods: A within-trial economic evaluation using data on health resource use and quality of life captured as part of the BEEP trial alongside the trial data. Parents/carers of 1394 infants born to families at high risk of atopic disease were randomised 1:1 to the emollient group, which were advised to apply emollient (Doublebase Gel or Diprobase Cream) to their child at least once daily to the whole body during the first year of life or usual care. Both groups received advice on general skin care. The main economic outcomes were incremental cost-effectiveness ratio (ICER), defined as incremental cost per percentage decrease in risk of eczema in the primary cost-effectiveness analysis. Secondary analysis, undertaken as a cost-utility analysis, reports incremental cost per Quality-Adjusted Life Year (QALY) where child utility was elicited using the proxy CHU-9D at 2 years., Results: At 2 years, the adjusted incremental cost was £87.45 (95% CI -54.31, 229.27) per participant, whilst the adjusted proportion without eczema was 0.0164 (95% CI -0.0329, 0.0656). The ICER was £5337 per percentage decrease in risk of eczema. Adjusted incremental QALYs were very slightly improved in the emollient group, 0.0010 (95% CI -0.0069, 0.0089). At 5 years, adjusted incremental costs were lower for the emollient group, -£106.89 (95% CI -354.66, 140.88) and the proportion without eczema was -0.0329 (95% CI -0.0659, 0.0002). The 5-year ICER was £3201 per percentage decrease in risk of eczema. However, when inpatient costs due to wheezing were excluded, incremental costs were lower and incremental effects greater in the usual care group., Conclusions: In line with effectiveness endpoints, advice given in the BEEP trial to apply daily emollient during infancy for eczema prevention in high-risk children does not appear cost-effective., (© 2023 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Children with severe atopic dermatitis (AD) have a multidimensional disease burden., Objective: Here we assess the clinically meaningful improvements in AD signs, symptoms, and quality of life (QoL) in children aged 6-11 years with severe AD treated with dupilumab compared with placebo., Methods: R668-AD-1652 LIBERTY AD PEDS was a randomized, double-blinded, placebo-controlled, parallel-group, phase III clinical trial of dupilumab with concomitant topical corticosteroids (TCS) in children aged 6-11 years with severe AD. This post hoc analysis focuses on 304 patients receiving either dupilumab or placebo with TCS and assessed the percentage of patients considered responsive to dupilumab treatment at week 16., Results: At week 16, almost all patients receiving dupilumab + TCS (95%) demonstrated clinically meaningful improvements in AD signs, symptoms, or QoL compared with placebo + TCS (61%, p < 0.0001). Significant improvements were seen as early as week 2 and sustained through the end of the study in the full analysis set (FAS) and the subgroup of patients with an Investigator's Global Assessment score greater than 1 at week 16., Limitations: Limitations include the post hoc nature of the analysis and that some outcomes were not prespecified; the small number of patients in some subgroups potentially limits generalizability of findings., Conclusion: Treatment with dupilumab provides significant and sustained improvements within 2 weeks in AD signs, symptoms, and QoL in almost all children with severe AD, including those who did not achieve clear or almost clear skin by week 16., Trial Registration: NCT03345914. Video Abstract: Does dupilumab provide clinically meaningful responses in children 6 to 11 years old with severe atopic dermatitis? (MP4 99484 kb)., (© 2023. The Author(s).)

Introduction: Atopic dermatitis (AD) is heterogeneous in distribution pattern and clinical features. This analysis assessed the effect of dupilumab on the extent and severity of AD across various signs (erythema, edema/papulation, excoriation, lichenification) in different anatomical regions (head and neck, trunk, upper extremities, lower extremities) in patients aged 6 months to 5 years., Methods: In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo with concomitant low-potency topical corticosteroids (TCS) every 4 weeks for 16 weeks. Changes in AD signs across anatomical regions were assessed using unweighted Eczema Area and Severity Index (EASI) body region scores., Results: Overall, 162 patients were randomized to dupilumab (n = 83) or placebo (n = 79). A significant improvement in least squares mean EASI area score was seen by week 2 in all four anatomical regions (P < 0.0001 for dupilumab vs. placebo) and sustained throughout treatment. Least squares mean EASI sign scores in erythema, excoriations, and infiltration/papulation showed significant improvement by week 2 in all regions (P < 0.001), while lichenification showed significant improvement in all regions by week 4 (P < 0.001)., Conclusion: Dupilumab use with concomitant low-potency TCS treatment resulted in rapid and consistent improvement in AD signs in all anatomical regions, in patients aged 6 months to 5 years with moderate-to-severe AD., Trial Registration: ClinicalTrials.gov Identifier: NCT03346434 Part B., (© 2023. The Author(s).)

Background: Early prediction of therapeutic response can optimize treatment strategies in atopic dermatitis (AD). Baricitinib is approved for moderate-to-severe AD in Europe, Japan and other countries., Objectives: To identify early clinical improvements that can reliably predict a later clinical response to baricitinib in adults with moderate-to-severe AD., Methods: Using data from one topical corticosteroid combination study [BREEZE-AD7 (NCT03733301)] and data pooled from two monotherapy studies [(BREEZE-AD1 (NCT03334396) and BREEZE-AD2 (NCT03334422)], we calculated the sensitivity and specificity, along with the positive predictive value (PPV) and negative predictive value (NPV), of predefined changes in single and combined clinical scores at weeks 2, 4 and 8, to predict clinical response at week 16. Clinical response was defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI 75), ≥ 4-point improvement in Itch Numeric Rating Scale (Itch NRS ≥ 4), or a combination of both., Results: Composite predictors had higher predictive accuracy for week 16 response outcomes than did single parameters. This was evident as early as week 4 for the combination of EASI 50 or Itch NRS ≥ 3 and of validated Investigator Global Assessment for AD (vIGA-AD) score ≤ 2 or Itch NRS ≥ 3 (sensitivity 87-100%; NPV 68-100%). The predictive accuracy of these composite clinical predictors for week 16 response outcomes was highest at week 8 (sensitivity 92-100%; NPV 80-100%). At both weeks 4 and 8, EASI 50 or Itch NRS ≥ 3 had higher sensitivity and NPV than did vIGA-AD score ≤ 2 or Itch NRS ≥ 3., Conclusions: Improvement in signs and symptoms early during treatment with baricitinib 4 mg once daily predicts clinical response at week 16, providing a tool for dermatologists when choosing treatment strategies for patients with moderate-to-severe AD., Competing Interests: Conflicts of interest T.B. has acted as speaker, and/or consultant and/or investigator for AbbVie, Almirall, AnaptysBio, Arena Pharmaceuticals Ltd, Asana Biosciences, Astellas Pharma, Bayer Health, BioVerSys, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Dermavant/Roivant, Dermtreat, Domain Therapeutics, DS Pharma, Eli Lilly and Company, Galapagos/MorphoSys, Galderma, Glenmark Pharmaceuticals, GSK, Incyte, Kymab, L’Oréal, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Pierre Fabre, RAPT Therapeutics/FLX Bio, Sanofi/Regeneron and UCB; and he is founder of the nonprofit biotech company Davos Biosciences. J.P.T. is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Aslan Pharmaceuticals, Eli Lilly and Company, LEO Pharma, OM Pharma, Pfizer, Regeneron, Sanofi/Genzyme and UNION Therapeutics; is a speaker for AbbVie, Almirall, Eli Lilly and Company, LEO Pharma, Pfizer, Regeneron and Sanofi/Genzyme; and has received research grants from Pfizer, Regeneron and Sanofi/Genzyme. A.D.I. is a consultant/speaker for AbbVie, Almirall, Arena, Benevolent AI, LEO Pharma, Lilly, Pfizer and Regeneron. Y.T. has received fees for lectures from Eli Lilly Japan K.K., Kyowa Kirin Co., Ltd., Maruho Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Sanofi K.K., Taiho Pharmaceutical Co., Ltd. and Torii Pharmaceutical Co., Ltd. Y.F.C., L.S., A.S. and E.R. are employees of and shareholders in Eli Lilly and Company. M.J.C. has served as a clinical trial investigator for Astellas Pharma, Atopix, Galapagos NV, Harvey Water Softeners, Hyphens Pharma, Johnson & Johnson, Kymab, LEO Pharma, L’Oréal, Novartis, Oxagen, Perrigo, Pfizer, Reckitt Benckiser, Regeneron and Sanofi Genzyme; and has served as a consultant for Astellas, Atopix Therapeutix Limited, Boots, Dermavant Sciences, Eli Lilly, Galapagos NV, Galderma, Harvey Water Softeners, Hyphens Pharma, Johnson & Johnson, Kymab, LEO Pharma, L’Oréal, Menlo Therapeutics, Novartis, Oxagen, Perrigo, Pfizer Inc., Procter & Gamble, Reckitt Benckiser, Regeneron, Sanofi/Genzyme and UCB., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Competing Interests: Conflicts of interest See Appendix S1 for full Conflicts of Interest list.

Crisaborole 2% ointment is a non-steroidal treatment for mild-moderate atopic dermatitis (AD) and may produce fewer adverse effects than topical corticosteroids (TCS). We used PS-OCT to quantify dermal collagen at baseline and after 29 days of treatment with crisaborole and betamethasone valerate (BMV), in 32 subjects. PS-OCT detected a mean increase 1 × 10-6, 95% CI (6.3, 1.37) × 10-6 in dermal birefringence following TCS use (p < 0.0001, ad-hoc, not powered), whereas a change of -4 × 10-6, 95% CI (-32, 24) × 10-6 was detected for crisaborole (p = 0.77, ad-hoc, not powered). These results could suggest a differential effect on dermal collagen between the two compounds. PS-OCT may thus find an important role in safety assessment of novel AD treatment' and larger trials are warranted., Competing Interests: Stephen J. Matcher, Simon G. Danby and Michael J. Cork disclose that they are in receipt of funding from Pfizer Inc., (Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

Background: Traditional systemic immunosuppressants and advanced therapies improve signs and symptoms of moderate-to-severe atopic dermatitis (AD). However, data are limited in severe and/or difficult-to-treat AD. In the phase 3 JADE COMPARE trial of patients with moderate-to-severe AD receiving background topical therapy, once-daily abrocitinib 200 mg and 100 mg showed significantly greater reductions in the symptoms of AD than placebo and significantly greater improvement in itch response (with abrocitinib 200 mg) than dupilumab at week 2., Objective: This study assessed the efficacy and safety of abrocitinib and dupilumab in a subset of patients with severe and/or difficult-to-treat AD in a post hoc analysis of the JADE COMPARE trial., Methods: Adults with moderate-to-severe AD received once-daily oral abrocitinib 200 mg or 100 mg, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo with concomitant medicated topical therapy. Severe and/or difficult-to-treat AD subgroups were classified by baseline characteristics [Investigator's Global Assessment (IGA) 4, Eczema Area and Severity Index (EASI) > 21, failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids), percentage of body surface area (%BSA) > 50, upper quartiles of EASI (EASI > 38) and %BSA (%BSA > 65), and combined subgroup of IGA 4, EASI > 21, and %BSA > 50, and failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids)]. Assessments included IGA score of 0 (clear) or 1 (almost clear) and a ≥ 2-point improvement from baseline, ≥ 75% and ≥ 90% improvement from baseline in EASI (EASI-75 and EASI-90), ≥ 4-point improvement from baseline in Peak Pruritus-Numerical Rating Scale (PP-NRS4), time to PP-NRS4, least squares mean (LSM) change from baseline in 14-day PP-NRS (days 2-15), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI) up to week 16., Results: The proportion of patients achieving IGA 0/1, EASI-75, and EASI-90 responses was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.05) across all subgroups with severe and/or difficult-to-treat AD. Across most subgroups, PP-NRS4 response was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.01); the time to achieve this response was shorter with abrocitinib 200 mg (range 4.5-6.0 days) than abrocitinib 100 mg (range 5.0-17.0 days), dupilumab (range 8.0-11.0 days), and placebo (range 3.0-11.5 days). LSM change from baseline in POEM and DLQI was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.001) across all subgroups. Clinically meaningful differences were observed between abrocitinib and dupilumab for most evaluated endpoints across several subgroups, including in patients who failed or were intolerant to prior systemic therapy., Conclusions: Abrocitinib provided rapid and substantially greater improvements in skin clearance and quality of life compared with placebo and dupilumab in subgroups of patients with severe and/or difficult-to-treat AD. These findings support the use of abrocitinib for severe and/or difficult-to-treat AD., Trial Registration: ClinicalTrials.gov, NCT03720470., (© 2023. The Author(s).)

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the general population. Skin barrier dysfunction is the central abnormality leading to AD. The cause of skin barrier dysfunction is complex and rooted in genetic mutations, interactions between the immune pathway activation and epithelial cells, altered host defense mechanisms, as well as environmental influences that cause epithelial cell activation and release of alarmins (such as thymic stromal lymphopoietin) that can activate the type 2 immune pathway, including generation of interleukins 4 and 13, which induces defects in the skin barrier and increased allergic inflammation. These inflammatory pathways are further influenced by environmental factors including the microbiome (especially Staphylococcus aureus), air pollution, stress, and other factors. As such, AD is a syndrome involving multiple phenotypes, all of which have in common skin barrier dysfunction as a key contributing factor. Understanding mechanisms leading to skin barrier dysfunction in AD is pointing to the development of new topical and systemic treatments in AD that helps keep skin borders secure and effectively treat the disease., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The effectiveness of emollients for preventing atopic dermatitis/eczema is controversial. The Barrier Enhancement for Eczema Prevention trial evaluated the effects of daily emollients during the first year of life on atopic dermatitis and atopic conditions to age 5 years., Methods: 1394 term infants with a family history of atopic disease were randomized (1:1) to daily emollient plus standard skin-care advice (693 emollient group) or standard skin-care advice alone (701 controls). Long-term follow-up at ages 3, 4 and 5 years was via parental questionnaires. Main outcomes were parental report of a clinical diagnosis of atopic dermatitis and food allergy., Results: Parents reported more frequent moisturizer application in the emollient group through to 5 years. A clinical diagnosis of atopic dermatitis between 12 and 60 months was reported for 188/608 (31%) in the emollient group and 178/631 (28%) in the control group (adjusted relative risk 1.10, 95% confidence interval 0.93 to 1.30). Although more parents in the emollient group reported food reactions in the previous year at 3 and 4 years, cumulative incidence of doctor-diagnosed food allergy by 5 years was similar between groups (92/609 [15%] emollients and 87/632 [14%] controls, adjusted relative risk 1.11, 95% confidence interval 0.84 to 1.45). Findings were similar for cumulative incidence of asthma and hay fever., Conclusions: Daily emollient application during the first year of life does not prevent atopic dermatitis, food allergy, asthma or hay fever., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Importance: Erythrodermic atopic dermatitis (AD) is a severe AD subtype defined by extensive skin involvement, leading to complications and sometimes hospitalization., Objective: To assess dupilumab's efficacy and safety in patients with erythrodermic AD in clinical trials., Design, Setting, and Participants: This post hoc analysis included patients enrolled in 6 multicenter, multinational, randomized, double-blind, placebo-controlled trials. Patients included in this analysis met erythrodermic AD criteria of 90% or greater body surface area (BSA) affected by AD and Global Individual Sign Score for erythema of 1 or higher. Data analyses for this post hoc analysis were conducted between March 5, 2019, and October 24, 2020., Interventions: Dupilumab once weekly or every 2 weeks, or placebo, either as monotherapy or with concomitant topical corticosteroids (TCS)., Main Outcomes and Measures: Efficacy (BSA, Eczema Area and Severity Index [EASI] score, Peak Pruritus Numerical Rating Scale [PP-NRS] score), changes in serum biomarkers (thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase), and safety (incidence of adverse events) at week 16. Data were pooled within each regimen; monotherapy and concomitant TCS results are shown separately., Results: Of 3075 randomized patients, 209 met criteria for erythrodermic AD at baseline, with the median age being 31 and 39 years in the monotherapy and concomitant TCS trials, respectively, similar to the overall populations (34 and 36 years, respectively); 71.3% (n = 97) and 74.0% (n = 54) of patients, respectively, were male (compared with 58.7% and 60.6% in the overall populations). In patients with erythrodermic AD, dupilumab once weekly and every 2 weeks vs placebo significantly improved percentage of BSA affected by AD (least squares mean percent change [SE]) with monotherapy (-42.0% [7.7%] and -39.9% [6.5%] vs -17.2% [11.0%]; P = .03) and concomitant TCS (-63.2% [6.7%] and -56.1% [9.1%] vs -14.5% [7.3%]; P < .001); EASI score with monotherapy (-58.5% [9.0%] and -58.3% [7.9%] vs -22.3% [12.4%]; P = .004 and P = .003, respectively) and concomitant TCS (-78.9% [7.8%] and -70.6% [10.1%] vs 19.3% [8.2%]; P < .001); and PP-NRS score in monotherapy (-45.9% [7.8%] and -33.9% [6.6%] vs -0.6% [9.4%]; P < .001) and concomitant therapy (-53.0% [8.1%] and -55.7% [10.8%] vs -26.0% [8.8%]; P = .006 and P = .01, respectively). Nominally statistically significant improvement was seen as early as week 1 (EASI and PP-NRS scores with monotherapy). Biomarker levels were significantly reduced vs placebo. The most frequent adverse events in dupilumab-treated patients were injection-site reaction, conjunctivitis, and nasopharyngitis., Conclusions and Relevance: In this post hoc analysis of 6 randomized clinical trials, treatment with dupilumab resulted in rapid, sustained improvements in AD signs and symptoms with acceptable safety in patients with erythrodermic AD, similar to those in the trials' overall patient population., Trial Registration: ClinicalTrials.gov Identifiers: NCT01859988, NCT02277743, NCT02277769, NCT03054428, NCT02260986, NCT02755649.