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Atopic dermatitis has a well-known association with mental health comorbidities. This article reviews the mental health interventions currently available to patients and caregivers, including the use of multidisciplinary clinics and peer support programmes. Future research is needed to understand the efficacy of these interventions, the optimal formats and the accessibility of mental health resources. Atopic dermatitis (AD) is associated with high levels of psychosocial burden, often resulting in poor mental health outcomes. Despite this association, few studies have evaluated the efficacy of mental health interventions within this population. Utilization of multidisciplinary and peer-led support, in addition to equipping patients with psychological tools, may be beneficial in improving mental health outcomes. Future research is needed to determine which interventions and formats are desired by, effective in and accessible to patients and caregivers with AD. [ABSTRACT FROM AUTHOR]

Janus kinase (JAK) refers to a family of tyrosine kinases that are involved in the production of proinflammatory mediators in response to various extracellular signals. The JAK–signal transducer and activator of transcription (STAT) pathway is an appealing target in many inflammatory illnesses as this pathway modulates immune cell activation and T-cell-mediated inflammation in response to several cytokines. The practical considerations of prescription for topical and oral JAK inhibitors (JAKis) in atopic dermatitis, vitiligo and psoriasis have been covered in prior publications. Currently, the US Food and Drug Administration has approved the topical JAKi ruxolitinib for atopic dermatitis and nonsegmental vitiligo. None of the remaining first- or second-generation topical JAKis have been approved for topical application in any dermatological indications so far. For this review, the PubMed database was searched using 'topical' and 'JAK inhibitor' or 'Janus kinase inhibitor' or the names of individual drug molecules as the keyword in the title with no date limits. The description of topical JAKi usage in dermatology from the literature was evaluated in each abstract. The current review concentrates on emphasizing the rising use of topical JAKis in both approved and off-label dermatological applications for both old and novel conditions. Currently, the Food and Drug Administration has approved the topical Janus kinase inhibitor (JAKi) ruxolitinib for atopic dermatitis and nonsegmental vitiligo. None of the remaining first- or second-generation topical JAKis have been approved for topical application in any dermatological indications so far. The current review concentrates on emphasizing the rising use of topical JAKis in both approved and off-label dermatological applications for both old and novel conditions. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) in people with skin of colour can appear psoriasiform, lichenoid, scaly or papular, with a violaceous colour and there is a higher prevalence of post-inflammatory dyspigmentation compared with affected individuals of White ethnicities, which can limit the use of current severity assessment tools. Greater participation from patients of different ethnicities in clinical trials is needed; with adequate representation, future studies may be able to better characterize potential differences in AD between different ethnic groups, as well as differences in treatment response. Recent advances in atopic dermatitis (AD) present the condition as a heterogeneous disease of distinct endotypes across ethnic groups. AD in people with skin of colour may appear psoriasiform, lichenoid, scaly or papular, with a violaceous colour and there is a higher prevalence of post-inflammatory dyspigmentation compared with affected individuals of White ethnicity. These differences in clinical presentation may limit the use of AD assessment tools in people with skin of colour, leading to the potential for misdiagnosis and underestimation of severity, particularly in relation to assessment of erythema. Recent targeted therapies for AD have been studied in multiple ethnic groups; however, ethnicity-based subgroup analysis is often not performed. Further research is required to understand whether treatment responses or safety may differ among ethnic groups. [ABSTRACT FROM AUTHOR]

Background Limited data are available regarding patient-centred dosing of dupilumab for atopic dermatitis (AD) in daily practice. Objectives To evaluate our patient-centred dupilumab dosing regimen in daily practice, to assess prognostic factors for successful tapering and to estimate medication-related cost savings. Methods This prospective multicentre study included adult patients with AD, participating in the BioDay registry, treated with dupilumab for ≥ 1.3 years. Interval prolongation was considered in the case of dupilumab standard dose for ≥ 1 year and persistent controlled AD [Eczema Area and Severity Index (EASI) ≤ 7; ≥ 6 months]. Primary endpoints were the mean EASI and Numeric Rating Scale (NRS)-pruritus after the start of tapering. Prognostic factors for successful tapering were analysed with logistic regression and a cost-savings analysis was performed. Results A total of 595 patients were included, of whom 401 patients [mean EASI 2.5 (SD 2.3); NRS-pruritus of 2.4 (SD 1.9) at the start of tapering] prolonged their dupilumab interval. In 83.3% of these patients tapering was successful; most patients used dupilumab every 3 or 4 weeks (Q3W/Q4W). A significant small increase was observed for EASI (highest mean 3.5) and NRS-pruritus (highest mean 3.2) (P < 0.001); however, scores remained low. Predicting successful tapering showed nonsignificant odds ratios for all incorporated variables. The estimated cost savings was €3 977 033.98 for 401 patients between January 2019 and June 2022. Conclusions This study showed successful tapering of dupilumab in 83.3% of patients with AD who attempted tapering, while maintaining controlled disease and with the majority using Q3W/Q4W. Interval prolongation can be beneficial both for the patient and from a socio-economic perspective. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by scaly, oozing skin and itch. In moderate-to-severe AD, treatment options have been historically very limited and off-label use has been a common method for disease management. For decades, ciclosporin A was the only systemic immunosuppressive drug approved in most European countries to address this major unmet medical need. However, increased understanding of the pathophysiology of AD has led to a revolution in the treatment of this potentially debilitating disease. Following the approval of the first biological therapy for AD in 2017, there has been a rapid expansion of compounds under development and four additional systemic therapies have been approved in Europe and the USA within the past 3 years alone. In this review, we underscore how key breakthroughs have transformed the therapeutic landscape of AD, leading to a major expansion of type 2 immunity-targeted biological therapies, exploration of neuroimmune modulatory agents, and interest in Janus kinase inhibition. [ABSTRACT FROM AUTHOR]

Background Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear. Objectives To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis. Methods We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case–control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis. Results We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety – one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09–2.40, 95% prediction intervals (PIs) 0.62–4.23, I 2 = 24.90%, τ 2 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56–3.25, 95% PI 0.21–24.23, I 2 = 0.00%, τ 2 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32–5.07, 95% PI 0.00–3956.27, I 2 = 61.90%, τ 2 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33–2.94, I 2 = 0.00%, τ 2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05–1.25, I 2 0.00%, τ 2 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents). Conclusions Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear. [ABSTRACT FROM AUTHOR]

Background: Tralokinumab is a fully human monoclonal antibody that neutralizes the activity of interleukin‐13, a key pathogenic driver of atopic dermatitis (AD). Clinical trials including adults with moderate‐to‐severe AD, of up to 52 weeks' duration, showed tralokinumab was efficacious and well tolerated. Objectives: To characterize the safety profile of tralokinumab for the treatment of moderate‐to‐severe AD. Methods: Safety and laboratory measures were assessed in pooled analyses of phase II and III placebo‐controlled clinical trials of tralokinumab in moderate‐to‐severe AD (NCT02347176, NCT03562377, NCT03131648, NCT03160885, NCT03363854). Results: In total, 2285 patients were randomized in the initial treatment periods up to 16 weeks (1605 tralokinumab, 680 placebo). The frequencies of any adverse event (AE) were 65·7% for tralokinumab and 67·2% for placebo. The respective rates were 640 and 678 events per 100 patient‐years of exposure (ep100PYE); rate ratio 1·0, 95% confidence interval (CI) 0·9–1·1. Serious AEs occurred in 2·1% of patients with tralokinumab and 2·8% with placebo (7·4 and 11·9 ep100PYE; rate ratio 0·7, 95% CI 0·4–1·2). The most common AEs occurring at a higher frequency and rate with tralokinumab vs. placebo were: viral upper respiratory tract infection (15·7% vs. 12·2%; 65·1 vs. 53·5 ep100PYE); upper respiratory tract infection (5·6% vs. 4·8%; 20·8 vs. 18·5 ep100PYE); conjunctivitis (5·4% vs. 1·9%; 21·0 vs. 6·9 ep100PYE); and injection‐site reaction (3·5% vs. 0·3%; 22·9 vs. 4·0 ep100PYE). Some events in safety areas of interest occurred at a lower frequency and rate with tralokinumab vs. placebo: skin infections requiring systemic treatment (2·6% vs. 5·5%; 9·7 vs. 22·8 ep100PYE), eczema herpeticum (0·3% vs. 1·5%; 1·2 vs. 5·2 ep100PYE), opportunistic infections (3·4% vs. 4·9%; 13·0 vs. 21·3 ep100PYE) and serious infections (0·4% vs. 1·1%; 1·3 vs. 3·7 ep100PYE). AEs did not increase with continued maintenance and open‐label treatment, including rates of common or serious AEs and AEs leading to study drug discontinuation. No clinically meaningful changes in mean laboratory measures were observed with treatment up to 1 year. Conclusions: Across the AD population pool from five clinical trials, tralokinumab was well tolerated, with consistent safety findings during treatment of patients with moderate‐to‐severe AD. The safety profile during prolonged tralokinumab treatment was consistent with that during the initial treatment period; the frequency of events did not increase over time. What is already known about this topic?Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin‐13, a key cytokine driving skin inflammation and epidermal barrier dysfunction in atopic dermatitis (AD).In clinical trials in moderate‐to‐severe AD, tralokinumab provided significant and early improvements in the extent and severity of AD and was well tolerated, with an overall safety profile comparable with placebo over 52 weeks. What does this study add?We report the frequency and rate of adverse events (AEs) from pooled observations of over 2000 patients from five phase II and phase III placebo‐controlled clinical trials of tralokinumab in moderate‐to‐severe AD.During initial treatment up to 16 weeks, the frequencies of any AE and of serious AEs were similar for tralokinumab and placebo. AE rates did not increase with continued treatment up to 52 weeks.Common AEs occurring more frequently with tralokinumab vs. placebo were viral and upper respiratory tract infection, conjunctivitis and injection‐site reaction. Some events occurred at a lower frequency and rate with tralokinumab vs. placebo, such as skin infections requiring systemic treatment, eczema herpeticum and opportunistic and serious infections.No clinically meaningful changes in mean laboratory measures were observed. [ABSTRACT FROM AUTHOR]

Summary: Background: Baricitinib, an oral selective Janus kinase (JAK)1 and JAK 2 inhibitor, was shown to improve the signs and symptoms of moderate‐to‐severe atopic dermatitis (AD). Objectives: To evaluate the efficacy and safety of baricitinib with background topical corticosteroids (TCS) in patients with moderate‐to‐severe AD and inadequate response, intolerance or contraindication to ciclosporin A (CA). Methods: In this double‐blind, randomized, placebo‐controlled, phase III study, patients were randomized 1: 1: 2: 1 to placebo (N = 93), baricitinib 1 mg (N = 93), 2 mg (N = 185) or 4 mg (N = 92) with background TCS. The primary endpoint was the proportion of patients receiving baricitinib 4 mg or 2 mg (+ TCS) vs. placebo + TCS who achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index (EASI 75) at week 16. Results: Baricitinib 4 mg + TCS was superior to placebo + TCS for EASI 75 (4 mg: 32%, placebo: 17%, P = 0·031) at week 16 and for improvements in itch, skin pain and number of night‐time awakenings owing to itch. Improvements were maintained through 52 weeks of treatment. Treatment‐emergent adverse events (TEAEs) were more common with baricitinib than placebo (+ TCS); most were mild or moderate. The most frequent TEAEs with baricitinib 4 mg + TCS were nasopharyngitis, herpes simplex, influenza and headache. No deaths or deep vein thromboses were reported. Conclusions: Baricitinib 4 mg + TCS improved the signs and symptoms of moderate‐to‐severe AD through 52 weeks of treatment in patients with inadequate response, intolerance or contraindication to CA. The safety profile was consistent with previous studies of baricitinib in moderate‐to‐severe AD. What is already known about this topic?Ciclosporin A is indicated for the treatment of atopic dermatitis that is refractory to topical therapies. However, its use is limited by safety concerns and it may not provide adequate response for some patients.Baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor, has been shown to improve the signs and symptoms of moderate‐to‐severe atopic dermatitis as a monotherapy or in combination with topical corticosteroids. What does this study add?Baricitinib combined with background low‐ or moderate‐potency topical corticosteroids provided improvements in the signs and symptoms of moderate‐to‐severe atopic dermatitis through 1 year of treatment in patients with a contraindication, intolerance or failure to respond to ciclosporin A.The most common treatment‐emergent adverse events with baricitinib 4 mg were nasopharyngitis, herpes simplex, influenza and headache.The safety profile was consistent with previous studies in patients with moderate‐to‐severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab is an antibody against interleukin‐4 receptor α, used in the treatment of atopic dermatitis (AD). Objectives: To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate‐to‐severe AD. Methods: In this randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0–1 and a reduction from baseline of ≥ 2 points at week 16. Results: Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37–32·65; P < 0·001]. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75–55·97; P < 0·001) and had ≥ 3‐point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26–55·34; P < 0·001) and ≥ 4‐point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69–45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment‐emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group. Conclusions: In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile. What is already known about this topic?Two randomized, placebo‐controlled phase III trials (SOLO 1 and SOLO 2) have demonstrated that dupilumab is effective and safe when used in the treatment of atopic dermatitis in adults.However, very few Chinese participants were included and, therefore, the efficacy and safety of dupilumab in this population is unclear. What does this study add?The findings of this randomized, placebo‐controlled phase III trial show that dupilumab is effective in improving the signs and symptoms of atopic dermatitis in adult Chinese patients and has a favourable safety profile in this population. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Pruritus is a hallmark of atopic dermatitis (AD), which affects disease severity and patient quality of life. In AD uncontrolled with first‐line topical therapies or in moderate to severe AD, systemic therapies are used; however, there is a paucity of head‐to‐head trials comparing the effectiveness of these therapies. The aim of this study was to compare the effectiveness of systemic therapies in relieving pruritus in moderate to severe AD in adults, using a meta‐analysis. The PubMed, EMBASE, Medline and CINAHL databases were searched from inception up to 31 May 2020 for randomized, placebo‐controlled trials investigating the effectiveness of systemic therapies on pruritus with moderate to severe AD in patients aged ≥ 16 years. In total, 26 studies (n = 5190 participants) were identified. Compared with placebo, there was a large and statistically significant (P < 0.001 for all) reduction in pruritus [standard mean difference (SMD); 95% CI] with dupilumab every 2 weeks (−0.88; −1.13 to −0.63), dupilumab every 2 weeks plus topical corticosteroids (−0.77; −0.91 to −0.62), dupilumab once weekly (−0.99; −1.29 to −0.68), dupilumab once weekly plus topical corticosteroids (−0.70; −0.81 to −0.59). There was also a large and statistically significant reduction with ciclosporin (−1.30; −2.34 to −0.26; P = 0.01) and a large, although not statistically significant reduction with azathioprine (−0.85; −2.07 to 0.35). There was a small reduction with both mepolizumab (−0.27; −0.89 to 0.35) and interferon‐γ (−0.31; −0.75 to 0.12). Of the investigational drugs, nemolizumab 2.0 mg/kg was the most effective (−8.13; −9.31 to −6.94). The majority of systemic therapies were superior to placebo in reducing pruritus. In particular, the dupilumab studies consistently showed large improvements in pruritus, while nemolizumab showed the strongest antipruritic effects. However, future head‐to‐head trials are required for conclusive evidence. [ABSTRACT FROM AUTHOR]

Summary: Background: Accurate assessment of atopic dermatitis (AD) severity is critical when initiating and monitoring therapy. Use of existing research tools such as the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD) is complex and time‐consuming in clinical practice. A previous analysis found the product of validated Investigator's Global Assessment (vIGA) and affected body surface area (BSA) to be an accurate and practical tool for routine assessment of paediatric AD. Objective: To evaluate the IGAxBSA composite as an alternative to EASI or SCORAD for assessment of AD disease severity and disease responsiveness. Methods: The relationship between IGAxBSA, EASI and SCORAD was assessed in a post hoc analysis of pooled data from the dupilumab clinical trial programme in adult and paediatric patients with moderate‐to‐severe AD who had received dupilumab or placebo, with or without topical corticosteroids (TCS). The trials are registered at ClinicalTrials.gov and EudraCT: LIBERTY AD SOLO 1 (NCT02277743, 2014‐001198‐15), LIBERTY AD SOLO 2 (NCT02277769, 2014‐002619‐40), LIBERTY AD SOLO‐CONTINUE (NCT02395133, 2014‐003384‐38), LIBERTY AD CHRONOS (NCT02260986, 2013‐003254‐24), LIBERTY AD CAFÉ (NCT02755649, 2015‐002653‐35), LIBERTY AD ADOL (NCT03054428, 2015‐004458‐16), LIBERTY AD PEDS (NCT03345914, 2016‐004997‐16), LIBERTY AD OLE (NCT01949311, 2013‐001449‐15) and LIBERTY AD PEDS OLE (NCT02612454, 2015‐001396‐40). Results: Using datapoints from pooled dupilumab randomized controlled trials (n = 3473) and open‐label extension trials (n = 3045), we found that IGAxBSA correlated well with EASI and SCORAD, irrespective of treatment group and race (white, Asian, black). IGAxBSA correlated better with objective measures (EASI, SCORAD) than with patient‐ or caregiver‐reported subjective measures. IGAxBSA correlated strongly with EASI and SCORAD in assessing disease change over time (r = 0·90, r = 0·76, respectively; P < 0·0001), and concordance between IGAxBSA‐50/75/90 and EASI‐50/75/90 was excellent (88–94%). Conclusions: IGAxBSA is a valid alternative for assessment of AD disease severity and response over time, compared with EASI or SCORAD in patients with AD, irrespective of race. [ABSTRACT FROM AUTHOR]

Summary: Background: Tralokinumab, a fully human IgG4 monoclonal antibody that specifically binds with high affinity to interleukin‐13, effectively reduces moderate‐to‐severe atopic dermatitis (AD) when given every 2 weeks. The incidence of conjunctivitis is elevated vs. placebo, but severity and aetiology have not been examined. Objective: To analyse conjunctivitis data recorded in five randomized, placebo‐controlled trials of tralokinumab in adult patients with moderate‐to‐severe AD. Methods: Overall, 2285 adults with AD were studied up to 16 weeks. Cochran–Mantel–Haenszel weights were applied to calculate the adjusted incidence of adverse events. Results: The incidence of conjunctivitis was higher (7·5%) with tralokinumab than with placebo (3·2%). Most events were mild or moderate in severity, and 78·6% and 73·9% of events resolved during the trial in the tralokinumab and placebo groups, respectively. Two (1·4%) events led to the permanent discontinuation of tralokinumab. An increased incidence of conjunctivitis, regardless of treatment group, was associated with more severe baseline AD, and history of allergic conjunctivitis/atopic keratoconjunctivitis, as well as the number of atopic comorbidities. Limitations: This analysis reports events up to week 16 only, with limited confirmation of conjunctivitis and its aetiology by an ophthalmologist, and insufficient reporting of ophthalmic treatments. Conclusions: Treatment with tralokinumab was associated with an increased incidence of conjunctivitis vs. placebo, but these cases were mostly mild and transient. Whatis already known about this topic? Ocular disorders, including conjunctivitis, occur more frequently in patients with atopic dermatitis (AD).When using the interleukin (IL)‐4 and IL‐13 receptor blocking biologic dupilumab, patients with AD in clinical trials and real‐world practice experience higher rates of conjunctivitis, which increases with baseline AD severity.Tralokinumab, a fully human monoclonal antibody, binds specifically to IL‐13 with high affinity.Various rates of conjunctivitis have been observed in different clinical trials of tralokinumab. Whatdoes this study add? This is the first investigation of conjunctivitis in phase III studies of a biological drug specifically targeting IL‐13, in contrast to dupilumab, which targets the IL‐4 and IL‐13 receptorsThe incidence of conjunctivitis was higher with tralokinumab (7·5%) vs. placebo (3·2%); most cases were mild and resolved, or were resolving during study treatment.Risk factors included high AD severity, history of conjunctivitis, disease biomarker levels, and number and type of atopic comorbiditiesThis is the first study to show that some atopic comorbidities have a greater influence on the risk of conjunctivitis than others. Linked Comment: R. Nguyen. Br J Dermatol 2022; 186:391–392. [ABSTRACT FROM AUTHOR]

Summary: Background: Children aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16‐week, randomized, placebo‐controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)‐4/IL‐13 signalling, significantly improved signs and symptoms with acceptable safety; longer‐term safety and efficacy data are lacking. Objectives: To report the pharmacokinetic profile and long‐term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD. Methods: Children (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open‐label, ascending‐dose, sequential cohort study and subsequent open‐label extension (OLE) study. Patients received single‐dose dupilumab 2 or 4 mg kg−1 followed by 8‐week pharmacokinetic sampling, then 2 or 4 mg kg−1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration–time profile and treatment‐emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus Numeric Rating Scale (PP‐NRS) score. Results: Of 38 children enrolled, 37 completed phase IIa and 33 continued to the OLE. Nonlinear, target‐mediated pharmacokinetics characterized dupilumab concentrations (week 24–48 mean serum concentrations: 2 mg kg−1, 61–77 mg L−1; 4 mg kg−1, 143–181 mg L−1). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. The most commonly reported TEAEs were nasopharyngitis (2 mg kg−1, 47%; 4 mg kg−1, 56%) and AD exacerbation (29% and 13%, respectively). Single‐dose dupilumab rapidly improved AD with further improvements through week 52. Mean EASI and PP‐NRS improved by −37%/−33% and −17%/−20% at week 2 (phase IIa) and −92%/−84% and −70%/−58% at week 52 (OLE), respectively. Conclusions: These safety and efficacy results support the use of dupilumab as a continuous long‐term treatment for children aged ≥ 6 to < 12 years with severe AD. What is already known about this topic?Severe atopic dermatitis (AD) has a marked negative impact on patient quality of life and can cause financial burden owing to a lack of effective treatments.Dupilumab significantly improved signs and symptoms of AD with an acceptable safety profile in a 16‐week randomized, double‐blind, placebo‐controlled phase III study in children aged ≥ 6 to < 12 years with severe AD. What does this study add?This study extends information on the safety, efficacy and pharmacokinetic profile of dupilumab treatment for up to 52 weeks in children aged ≥ 6 to < 12 years with severe AD.The results support the use of dupilumab as a continuous long‐term treatment for children aged ≥ 6 to < 12 years with severe AD. Linked Comment: Sibbald. Br J Dermatol 2021; 184:792–793. [ABSTRACT FROM AUTHOR]

Among the six patients who stopped treatment owing to AD remission, the median duration of treatment was 57 weeks (IQR 44-25-65-25). From a total of 968 patients treated with dupilumab during the study period, 150 patients (15-5%) discontinued treatment after a median treatment duration of 5 months [interquartile range (IQR) 3-10]. Dear Editor, Dupilumab, an anti-interleukin-4 monoclonal antibody, has shown a positive benefit-risk ratio when treating moderate-to-severe atopic dermatitis (AD) in clinical studies.1 High persistence for patients on dupilumab has recently been reported in a clinical practice setting, with 77% of patients remaining in treatment for 12 months in a retrospective study that included 1963 patients with AD; however, reasons for discontinuation were not investigated.2 Investigating the reasons for treatment discontinuation in chronic diseases permits the assessment of both the safety and the effectiveness of a given treatment in a clinical practice setting. [Extracted from the article]

During dupilumab treatment, Patient 1 presented with injection site reactions, manifesting as local mild erythema, swelling, which resolved without special treatment. Dear Editor, Atopic dermatitis (AD) is one of the most common skin disorders in children, with a prevalence of 25%-30%, and up to 33% of patients develop moderate to severe AD.1 Systemic treatment options may be needed in cases of moderate to severe AD, but none of the currently available medications is a long-term treatment option, as they are all restricted by potential drug toxicity. Off-label use of dupilumab for the treatment of moderate to severe atopic dermatitis in children aged below 6 years of age: a case series. [Extracted from the article]

A 29-year-old male, with chronic atopic dermatitis (AD), presented with a 2-week history of fatigue, pyrexia and weight loss. Examination showed eczematous patches with lichenified papules, erosions on the right shin and a new murmur. Blood cultures isolated methicillin-sensitive Staphylococcus aureus. Transthoracic echocardiography showed vegetation on the tricuspid valve (TV) that was adherent to the septal leaflet. He was treated for infective endocarditis, attributed to poorly controlled AD, with intravenous Flucloxacillin. Due to ongoing sepsis and pulmonary septic emboli, Clindamycin was added. He underwent TV repair; the septal leaflet was excised, and the remnant two leaflets were brought together with a ring. His patent foramen ovale was closed. His skin was treated with topical steroids and emollients. Right-sided endocarditis of an intact TV is uncommon in a non-intravenous drug user. Therefore, this novel case portrays the importance of aggressively managing AD as it is a risk factor for significant systemic infections. [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab, a human monoclonal antibody, blocks the shared receptor unit for interleukin‐4 and interleukin‐13. International phase II and III studies have evaluated the efficacy and safety of dupilumab in adults with moderate‐to‐severe atopic dermatitis (AD), but the effects of dupilumab in Japanese patients have not been reported. Objectives: To evaluate the efficacy and safety of dupilumab in Japanese patients with moderate‐to‐severe AD. Methods: We analysed the efficacy and safety of dupilumab in the Japanese cohorts of a 16‐week, phase IIb dose‐finding trial (AD‐1021; NCT01859988); a 16‐week, phase III, placebo‐controlled monotherapy trial (LIBERTY AD SOLO 1; NCT02277743) and a 52‐week, phase III, placebo‐controlled study of dupilumab with topical corticosteroids (LIBERTY AD CHRONOS; NCT02260986). Results: Twenty‐seven, 106 and 117 Japanese patients were enrolled in AD‐1021, SOLO 1 and CHRONOS, respectively. Baseline disease severity was numerically higher in the Japanese cohort than in the overall study population. Generally, dupilumab significantly improved signs and symptoms of AD, including pruritus and patient quality of life, compared with placebo in the Japanese cohort, consistent with the overall study population. The combined safety profile of dupilumab in the Japanese cohort was similar to that in the total study populations; dupilumab was associated with an increased incidence of injection‐site reactions and conjunctivitis compared with placebo. Dupilumab was associated with rapid reduction in thymus and activation‐regulated chemokine and gradual IgE reductions. Conclusions: Dupilumab alone or with topical corticosteroids improved signs and symptoms of AD, had an acceptable safety profile, and suppressed biomarkers of type 2 inflammation compared with placebo in Japanese adult patients with moderate‐to‐severe AD. What's already known about this topic? Differences in atopic dermatitis (AD) pathology have been reported between Asian and Western populations, in which distinct helper T‐cell activation profiles have been observed.International clinical studies in adults with moderate‐to‐severe AD have evaluated the efficacy and safety of dupilumab, which blocks interleukin‐4 and interleukin‐13, key molecules in type 2 inflammation.The effects of dupilumab in Japanese patients specifically have not yet been reported. What does this study add? Dupilumab alone or with topical corticosteroids improved signs and symptoms of AD and had an acceptable safety profile compared with placebo in Japanese patients with moderate‐to‐severe AD.The effects were comparable with those observed in the overall study population.Reported immunological differences in AD pathology in Asian patients may be secondary to type 2 immune activation. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Summary: Background: A long‐term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. Objectives: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate‐to‐severe atopic eczema, to assess the long‐term safety risk of these therapies in a routine clinical care setting. Methods: We describe a registry‐embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. Conclusions: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long‐term data on the safety of systemic immunomodulating therapies in patients with atopic eczema.Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long‐term safety profile against established therapies.Large numbers of patients with a long duration of follow‐up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries.We present a protocol for an investigator‐initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate‐to‐severe atopic eczema.This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab [a monoclonal antibody blocking the shared receptor subunit for interleukin (IL)‐4 and IL‐13] is approved for patients aged ≥ 12 years with inadequately controlled, moderate‐to‐severe atopic dermatitis (AD). Dupilumab trials of up to 52 weeks demonstrated efficacy and a favourable safety profile in patients with moderate‐to‐severe AD inadequately controlled with topical medications. Objectives: To further characterize the safety of dupilumab by evaluating clinical laboratory findings from three randomized, double‐blinded, placebo‐controlled phase III trials (LIBERTY AD SOLO 1 & 2 and LIBERTY AD CHRONOS). Methods: Patients were randomized 1 : 1 : 1 (SOLO 1 & 2) or 3 : 1 : 3 (CHRONOS) for 16 and 52 weeks, respectively, to dupilumab weekly, every 2 weeks or placebo. CHRONOS patients received a standardized concomitant topical corticosteroid regimen. Laboratory outcomes were summarized descriptively in 1376 patients from SOLO 1 & 2 and 740 from CHRONOS. Results: Treatment groups had similar results in baseline laboratory parameters. Platelets and neutrophils showed mild decreases from baseline in dupilumab vs. placebo groups. Some dupilumab‐treated patients had small transient increases in eosinophils. Grade 3 eosinophilia was reported in < 1% of dupilumab‐treated and placebo‐treated patients; no adverse events were associated with eosinophilia. Lactate dehydrogenase levels decreased from baseline during dupilumab treatment in all trials. No clinically meaningful changes were observed between treatment groups in other haematology, chemistry or urinalysis parameters. Conclusions: There were no clinically important changes in routine laboratory parameters that could be attributed to dupilumab. This study supports the use of dupilumab as a systemic treatment for moderate‐to‐severe AD that does not require laboratory monitoring. What's already known about this topic? Long‐term treatment of atopic dermatitis (AD) with conventional immunosuppressive agents is limited by the risk of significant side‐effects and a need for repeated tests to monitor haematological and/or organ (e.g. liver, kidney) toxicities.Dupilumab [a monoclonal antibody blocking the shared receptor subunit for interleukin (IL)‐4 and IL‐13] is approved for the treatment of patients with inadequately controlled, moderate‐to‐severe AD.In 16‐week and 52‐week studies, dupilumab demonstrated a positive risk/benefit profile in moderate‐to‐severe AD. What does this study add? This study is the first comprehensive analysis of dupilumab laboratory safety data of the 16‐week SOLO 1 & 2 (pooled N = 1376) and 52‐week CHRONOS (N = 740) trials, demonstrating an absence of clinically important changes in haematology, serum chemistry and urinalysis parameters in patients with moderate‐to‐severe AD treated with dupilumab.Our data support the use of dupilumab as a systemic treatment for the long‐term management of moderate‐to‐severe AD without routine laboratory monitoring in clinical practice. Respond to this article [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab (monoclonal antibody inhibiting IL‐4/IL‐13 signalling) is approved for use in adolescents aged ≥ 12 years with inadequately controlled moderate‐to‐severe atopic dermatitis (AD). Dupilumab significantly improved AD signs/symptoms in a 16‐week, randomised, placebo‐controlled phase III trial in adolescents (NCT03054428). Objectives: To characterize the pharmacokinetics of dupilumab, and long‐term safety and efficacy in adolescents. Methods: This was a global, multicentre, phase IIa, open‐label, ascending‐dose, sequential cohort study with a phase III open‐label extension (OLE) in adolescents with moderate‐to‐severe AD. In the phase IIa study, patients received one dupilumab dose (2 mg kg−1 or 4 mg kg−1) and 8 weeks of pharmacokinetic sampling. Thereafter, patients received the same dose weekly for 4 weeks, with 8‐week safety follow‐up. Patients then enrolled in the OLE, continuing 2 mg kg−1 or 4 mg kg−1 dupilumab weekly. Primary end points were dupilumab concentration–time profile and incidence of treatment‐emergent adverse events (TEAEs). Secondary outcomes included Eczema Area and Severity Index (EASI). Results: Forty adolescents received dupilumab in the phase IIa study; 36 enrolled in the OLE. Dupilumab showed nonlinear, target‐mediated pharmacokinetics. Mean ± SD trough dupilumab concentrations in serum at week 48 (OLE) were 74 ± 19 mg L−1 and 161 ± 60 mg L−1 for 2 mg kg−1 and 4 mg kg−1, respectively. Dupilumab was well tolerated over 52 weeks; the most common TEAEs were nasopharyngitis (week 52: 41% [2 mg kg−1], 47% [4 mg kg−1]) and AD exacerbation (29%, 42%). After one dupilumab dose in the phase IIa study, EASI improved from baseline to week 2 [mean ± SD reduction −34% ± 20% (2 mg kg−1) and −51% ± 29% (4 mg kg−1)]. With continuing treatment, EASI scores improved further [week 52: −85% ± 12% (2 mg kg−1) and −84% ± 20% (4 mg kg−1)]. Conclusions: In adolescents with moderate‐to‐severe AD, dupilumab's pharmacokinetic profile was similar to that in adults. These 52‐week safety and efficacy data support long‐term use of dupilumab in this patient population. What's already known about this topic? Adolescents with moderate‐to‐severe atopic dermatitis (AD) have high unmet medical need, with significant disease burden and limited treatment options.Dupilumab (monoclonal antibody against interleukin‐4 receptor α) is approved for the treatment of adolescents with moderate‐to‐severe AD who are inadequately responsive to standard of care (U.S.A.) or candidates for systemic therapy (European Union).A 16‐week, randomized, placebo‐controlled phase III trial in adolescents demonstrated significant improvements in AD signs/symptoms with an acceptable safety profile. What does this study add? These studies demonstrate the long‐term safety and efficacy of dupilumab in adolescents with moderate‐to‐severe AD for up to 52 weeks of treatment, thus extending and reinforcing the findings from the 16‐week dupilumab phase III trial.The data from these studies also support the use of dupilumab in combination with current standard of care (topical corticosteroids), which was not evaluated in the 16‐week phase III monotherapy trial. Linked Comment: Sibbald. Br J Dermatol 2020; 182:12–13. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. Objectives: To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. Methods: We evaluated randomized placebo‐controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). Results: In most AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. Conclusions: Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab‐treated patients require further study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD).In most dupilumab AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than those receiving placebo.Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare.Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add? This analysis confirms and extends the results of the individual clinical trials.Baseline disease‐related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation‐regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis.Patients who responded well to dupilumab had reduced incidence of conjunctivitis.Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab‐treated patients with AD. Linked Editorial: Chia‐Yu Chu. Br J Dermatol 2019; 181:436–437. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Lipid mediators, such as prostanoids and leukotrienes (LTs), exert a range of actions through their own receptors on cell surfaces in various pathophysiological conditions. It has been reported that the production of prostanoids and LTs is significantly elevated in the skin lesions of some chronic inflammatory skin diseases, such as atopic dermatitis (AD) and psoriasis, showing the possible involvement of these lipid mediators in the development of those diseases. Although the actual significance of these lipid mediators in humans is still unclear, the findings from studies in mice suggest diverse roles of the lipid mediators in the progression or regulation of these diseases. For example, in a mouse AD model, prostaglandin D2 inhibits the induction of Th2 cells through DP receptor on Langerhans cells, while it promotes infiltration of Th2 cells through chemoattractant receptor-homologous molecule expressed on Th2 cells. In a psoriasis model, thromboxane A2-TP signaling promotes psoriatic dermatitis by facilitating IL-17 production from γδ T cells. In this short review, we summarize the current findings on the roles of prostanoids and LTs in AD and psoriasis as revealed by studies in mice, and discuss the potential of these lipid mediators as therapeutic targets in humans. [ABSTRACT FROM AUTHOR]

Summary: Background: In the U.S.A., an Investigator's Global Assessment (IGA) score of ≤ 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab. Objectives: To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life. Methods: LIBERTY AD SOLO 1 and 2 were two 16‐week, randomized, double‐blind trials enrolling adult patients with moderate‐to‐severe AD (IGA ≥ 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient‐Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769. Results: At week 16, 278 of 449 dupilumab q2w‐treated patients (median age 36·0 years) and 396 of 443 placebo‐treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (−48·9% vs. −11·3%, P < 0·001), pruritus NRS (−35·2% vs. −9·1%, P < 0·001), affected BSA (−23·1% vs. −4·5%, P < 0·001), POEM score ≥ 4‐point improvement (57·4% vs. 21·0%, P < 0·001) and DLQI score ≥ 4‐point improvement (59·3% vs. 24·4%, P < 0·001). Conclusions: In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA ≤ 1 end point significantly underestimates clinically relevant dupilumab treatment effects. What's already known about this topic? An Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear skin) is considered the regulatory standard for treatment success in trials of patients with atopic dermatitis in the U.S.A.It is currently unknown whether patients receiving dupilumab treatment for moderate‐to‐severe atopic dermatitis derive clinical and quality‐of‐life benefit even if they have an end‐of‐treatment IGA score > 1. What's does this study add? This post hoc analysis of patients with an end‐of‐treatment IGA score > 1 from two randomized, placebo‐controlled trials showed that after 16 weeks of treatment dupilumab significantly improved their outcome measures compared with placebo, including measures of signs, symptoms and quality of life.These results show that the regulatory IGA ≤ 1 end point used in clinical trials significantly underestimates clinically relevant dupilumab treatment effects, underscoring potential limitations of the IGA scale. Linked Comment: de Bruin‐Weller. Br J Dermatol 2019; 181:12–13. Respond to this article [ABSTRACT FROM AUTHOR]

Dear Editor, Dupilumab (Dupixent®) is the first biological drug to be licensed for the treatment of adults with atopic dermatitis (AD). SP d sp I n i = 81; patients discontinued due to an AE ( I n i = 6), loss to follow-up ( I n i = 3), comorbidities ( I n i = 3) or death ( I n i = 2). Real-world effectiveness and tolerability of dupilumab in adult atopic dermatitis: a single-centre, prospective 1-year observational cohort study of the first 100 patients treated. [Extracted from the article]

Dear Editor, Dupilumab, an inhibitor of interleukin (IL)-4/13 activity, is a biological agent approved for the treatment of moderate-to-severe atopic dermatitis (AD).1 In this study, we aimed to assess the long-term effectiveness and safety of dupilumab in a real-world clinical setting. Primary effectiveness outcomes included the proportion of patients at week 52 achieving EASI improvements of 50%, 75% or 90% (EASI 50, EASI 75 or EASI 90). Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). [Extracted from the article]

Summary: Aim: Blauvelt et al. aimed to compare the long‐term efficacy and safety of dupilumab with medium‐potency topical corticosteroids (TCS) vs. placebo with TCS in adults with moderate‐to‐severe atopic dermatitis (AD). Setting and design: This multicentre randomized, double‐blinded, placebo‐controlled trial was conducted in hospitals, clinics and academic institutions across 161 sites in 14 countries. Study exposure: Adults with moderate‐to‐severe AD were randomly assigned (3: 1: 3) to receive subcutaneous dupilumab 300 mg once weekly plus TCS, dupilumab 300 mg every 2 weeks plus TCS or placebo plus TCS until week 52. Outcomes: Co‐primary efficacy end points were percentage of patients achieving Investigator's Global Assessment (IGA) 0/1 and 2 points or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI‐75) at week 16. Results: In total, 740 patients were included in the trial: 319 were randomly assigned to dupilumab once weekly, 106 to dupilumab every 2 weeks and 315 to the placebo arm. At week 16, more patients in the dupilumab groups achieved the co‐primary end points: IGA 0/1 [39% (n = 125) once‐weekly dosing, 39% (n = 41) every 2 weeks dosing vs. 12% (n = 39) receiving placebo; P < 0·0001] and EASI‐75 [64% (n = 204) and 69% (n = 73) vs. 23% (n = 73); P < 0·0001]. While no new safety signals were identified, adverse effects were noted in 261 (83%) of those receiving dupilumab once weekly plus TCS, 97 (88%) receiving dupilumab every 2 weeks plus TCS and 266 (84%) for those receiving placebo plus TCS. Rates of conjunctivitis, injection site reactions and local herpes simplex infections were higher in the dupilumab groups than in the placebo group. Conclusions: Blauvelt et al. concluded that dupilumab treatment added to TCS improved AD up to week 52 vs. TCS alone, and also demonstrated acceptable safety. [ABSTRACT FROM AUTHOR]

Summary: Background : JTE‐052 is a novel Janus kinase inhibitor presently under clinical development for the topical treatment of atopic dermatitis (AD). Objectives : To evaluate the efficacy and safety of JTE‐052 ointment in Japanese adult patients with AD. Methods : Patients with moderate‐to‐severe AD were randomized (2: 2: 2: 2: 1: 1) to receive JTE‐052 ointment at 0·25%, 0·5%, 1% or 3%, the vehicle ointment or tacrolimus 0·1% ointment (reference) twice daily for 4 weeks. The primary efficacy end point was the percentage change in modified Eczema Area Severity Index (mEASI) score from baseline at the end of treatment (EOT). Secondary efficacy end points included change from baseline in the pruritus numerical rating scale (NRS) score. Results : In total, 327 patients were enrolled. At EOT, the least‐squares mean percentage changes from baseline in mEASI score for JTE‐052 at 0·25%, 0·5%, 1% and 3% and the vehicle ointment were −41·7%, −57·1%, −54·9%, −72·9% and −12·2%, respectively. All JTE‐052 groups showed significant reductions of mEASI score vs. the vehicle group (P < 0·001 for all). In the tacrolimus group, the mean percentage change in mEASI score was −62·0%. The JTE‐052 groups also showed significant improvement in other parameters; notably, the pruritus NRS score was reduced as early as day 1 night‐time. JTE‐052 ointment at doses up to 3% was safe and well tolerated. Conclusions : Topical JTE‐052 markedly and rapidly improved clinical signs and symptoms in Japanese adult patients with moderate‐to‐severe AD, with a favourable safety profile. The study results indicate that topical JTE‐052 is a promising therapeutic option for AD. The trial registration number is JapicCTI‐152887. [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab, a human anti‐interleukin‐4 receptor alpha monoclonal antibody, significantly improved clinical signs and symptoms in adults with moderate‐to‐severe atopic dermatitis in a randomized, double‐blind, placebo‐controlled, phase IIa trial. Objectives: We evaluate health‐related quality of life (HRQoL) and correlation of HRQoL with secondary clinical and patient‐reported outcomes in a subset of patients from this trial of dupilumab. Methods: Patients were randomized to 300 mg weekly subcutaneous dupilumab or placebo for 12 weeks (trial registration: NCT01548404). The Quality of Life Index of Atopic Dermatitis (QoLIAD) score (exploratory outcome) and its correlation with efficacy outcomes [Eczema Area and Severity Index (EASI); primary end point; SCORing Atopic Dermatitis (SCORAD), SCORAD visual analogue scale (VAS) scores for sleep and pruritus, pruritus numerical rating scale (NRS) and 5‐dimensional pruritus] were assessed in 64 adults with moderate‐to‐severe atopic dermatitis. Results: Mean QoLIAD scores at baseline ± standard error (SE) were 13·3 ± 1·34 and 11·3 ± 1·09 for the placebo and dupilumab groups, respectively. Dupilumab significantly improved QoLIAD score after 12 weeks of treatment vs. placebo (mean % change from baseline in QoLIAD score ± SE: −64·0 ± 6·91 vs. –11·1 ± 9·31). Least squares mean % difference from baseline vs. placebo in QoLIAD score ±SE was −52·0 ± 11·43, P < 0·001). QoLIAD scores significantly correlated with changes in efficacy outcomes, including EASI (r = 0·44), 5‐dimensional pruritus (r = 0·49), pruritus NRS (r = 0·41), total SCORAD (r = 0·56) and SCORAD VAS scores for sleep (r = 0·47) and pruritus (r = 0·54); all P < 0·05. Conclusions: Dupilumab improved QoLIAD scores in adults with atopic dermatitis and was significantly associated with improvements in study outcomes. [ABSTRACT FROM AUTHOR]

All adult patients with moderate-to-severe AD receiving dupilumab treatment who visited our hospital between June 2018 and December 2018 were included in this study. The EASI score significantly decreased by 44% on average at 1 month and by 69% at 3 months; however, no significant decrease in the EASI scores for the head and neck was found at 1 month after starting dupilumab (Fig. c, d). We observed a mild injection-site reaction in one patient and hair regrowth in another patient with alopecia areata (we have previously reported on the latter patient).[4] No patients have discontinued dupilumab as of 1 March 2019. [Extracted from the article]

Prevention of conjunctivitis in patients with atopic dermatitis undergoing treatment with dupilumab: an Italian single-centre experience Atopic dermatitis (AD) is a chronic inflammatory skin disease,1 commonly related to other atopic manifestations such as food allergy, rhinitis, asthma and conjunctivitis.2 A large proportion of patients with AD (31%-56%) develop an episode of conjunctivitis in their lifetime, usually related to the severity of dermatitis.3 Conjunctivitis also appears to be one of the most frequent adverse events (AEs) in patients treated with dupilumab,4 a monoclonal antibody targeting interleukin (IL)-4 and IL-13, which has been approved for the treatment of several type 2 diseases in addition to AD, such as asthma, nasal polyposis and eosinophilic oesophagitis.5 Previous reports of randomized controlled trials (RCTs) revealed that the incidence of conjunctivitis was higher in participants with AD than in those with other type 2 diseases, for whom the incidence of conjunctivitis was comparable to the placebo group. Both patients recovered without needing to discontinue dupilumab therapy but at Week 52 of treatment, one of the two patients relapsed. [Extracted from the article]

Linked Articles: Wollenberg et al. Br J Dermatol 2021; 184:437–449. Silverberg et al. Br J Dermatol 2021; 184:450–463. [ABSTRACT FROM AUTHOR]

Linked Article: Simpson et al. Br J Dermatol 2020; 183:242–255. [ABSTRACT FROM AUTHOR]

The article offers information on the effect of dupilumab on atopic manifestations in patients treated for atopic dermatitis in real-life practice. It mentions the ophthalmological examination was abnormal for 10 patients at inclusion with one case of acute allergic conjunctivitis; and also mentions treatment for conjunctivitis requires collaboration with an experienced ophthalmologist.

A review of the article "Magnitude of benefit for topical crisaborole in the treatment of atopic dermatitis in children and adults does not look promising: a critical appraisal" by A. Ahmed is presented.

Linked Articles: Blauvelt and Shumel. Br J Dermatol 2018; 179:1423. Thomson et al. Br J Dermatol 2018; 178:897–902. [ABSTRACT FROM AUTHOR]

Linked Article: Thomson et al. Br J Dermatol 2018; 178:897–902. [ABSTRACT FROM AUTHOR]