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Background: Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile. Objective: We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program. Methods: Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed. Results: Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 103/mm3 before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1]). Conclusions: This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.] Clinical Trial Registration: NCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026). Plain Language Summary: Abrocitinib is an approved treatment for people with moderate or severe atopic dermatitis, also known as AD or atopic eczema. Abrocitinib is a tablet that is taken by mouth once a day. This safety analysis looked at the side effects of treatment in a large group of adults and adolescents with moderate or severe AD who took abrocitinib up to a maximum of almost 4 years. This analysis also looked at which people were more likely to have certain side effects after taking abrocitinib. The results from this analysis were similar to those of previous safety analyses with abrocitinib, with no new side effects. Infections such as shingles, pneumonia, or herpes simplex can occur during treatment with abrocitinib. Shingles was more likely to occur in people who previously had shingles before taking abrocitinib, or who took the higher dose of abrocitinib (200 mg), or were 65 years of age or older, or had certain blood test results, or lived in Asia. People who are 65 years of age or older and took abrocitinib were more likely to develop some types of cancer, have certain abnormal blood test results, or develop blood clots in the veins than people with AD who were younger and took abrocitinib. Current or former smokers with AD who took abrocitinib were more likely to develop skin cancer (but not melanoma) than people with AD who took abrocitinib but have never smoked. This analysis further shows that abrocitinib had manageable safety in patients with moderate-to-severe AD. Dex5AhfAxs29XQspjFnxYi Video abstract: Integrated safety update of abrocitinib in 3802 patients with moderate-to-severe atopic dermatitis: data from more than 5200 patient-years with up to 4 years of exposure (MP4 63720 KB) [ABSTRACT FROM AUTHOR]

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). Plain Language Summary: Atopic dermatitis (AD) is a chronic inflammatory skin disease that often results in a high disease burden in young children and their families. Patients often need long-term treatment to control their disease symptoms, including itch and rash. Dupilumab treatment for 16 weeks has shown benefits in children aged 6 months to 5 years with moderate-to-severe AD, with an acceptable safety profile. As AD is likely to continue from childhood into adolescence and adulthood, there is a need for data supporting long-term use of dupilumab in young children. In this study, children who completed the 16-week study continued dupilumab treatment for up to 1 year, receiving 200 mg or 300 mg of dupilumab (depending on the child's bodyweight) every 4 weeks. Through the year of treatment, 78.2% of patients reported at least one side effect, most of which were mild or moderate. Only one patient interrupted treatment because of severe skin rash (hives), which was resolved in 1 day. At the end of the year, 36.2% of patients had clear or almost clear skin, and almost all (96.6%) achieved at least 50% improvement in their extent and severity of disease. Additionally, 79.3%, and 58.6% had at least 75% or 90% improvement in their extent and severity of disease. In summary, consistent with results seen in adults, adolescents, and older children, this study showed that 1-year dupilumab treatment provides continued benefits with an acceptable safety profile. These results support long-term continuous use of dupilumab in children aged 6 months to 5 years with moderate-to-severe AD. 5SqqskjZPmoHiNU8WnfbXp What is the long-term safety and efficacy profile in young children with moderate-to-severeatopic dermatitis treated with dupilumab? [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD), a highly pruritic, inflammatory skin disease, affects approximately 7% of adolescents globally. A topical formulation of ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated safety and efficacy among adolescents/adults in two phase 3 studies (TRuE-AD1/TRuE-AD2). Objective: To describe safety and efficacy of 1.5% ruxolitinib cream versus vehicle and long-term disease control of ruxolitinib cream among adolescents aged 12–17 years from pooled phase 3 study data. Methods: Patients [≥ 12 years old with AD for ≥ 2 years, Investigator's Global Assessment score (IGA) 2/3, and 3–20% affected body surface area (BSA) at baseline] were randomized 2:2:1 to ruxolitinib cream (0.75%/1.5%) or vehicle for 8 weeks of continuous use followed by a long-term safety (LTS) period up to 52 weeks with as-needed use. Patients originally applying vehicle were rerandomized 1:1 to 0.75%/1.5% ruxolitinib cream. Efficacy measures at week 8 included IGA treatment success (IGA-TS; i.e., score of 0/1 with ≥ 2 grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index (EASI-75), and ≥ 4-point improvement in itch numerical rating scale (NRS4). Measures of disease control during the LTS period included IGA score of 0 (clear) or 1 (almost clear) and percentage affected BSA. Safety was assessed throughout the study. Results: Of 1249 randomized patients, 245 (19.6%) were aged 12–17 years. Of these, 45 patients were randomized to vehicle and 92 patients to 1.5% ruxolitinib cream. A total of 104/137 (75.9%) patients continued on 1.5% ruxolitinib cream in the LTS period [82/92 (89.1%) continued on 1.5% ruxolitinib cream; 22/45 (48.9%) patients on vehicle were reassigned to 1.5% ruxolitinib cream], and 83/104 (79.8%) of these patients completed the LTS period. At week 8, substantially more patients who applied 1.5% ruxolitinib cream versus vehicle achieved IGA-TS (50.6% versus 14.0%), EASI-75 (60.9% versus 34.9%), and NRS4 (52.1% versus 17.4%; P = 0.009). The mean (SD) reduction in itch NRS scores was significantly greater in patients applying 1.5% ruxolitinib cream versus vehicle from day 2 [− 0.9 (1.9) versus −0.2 (1.4); P = 0.03]. During the LTS period, mean (SD) trough steady-state ruxolitinib plasma concentrations at weeks 12/52 were 27.2 (55.7)/15.5 (31.5) nM. The percentage of patients achieving IGA score of 0 or 1 was sustained or further increased with 1.5% ruxolitinib cream; mean affected BSA was generally low (< 3%; i.e., mild disease). Through 52 weeks, application site reactions occurred in 1.8% of adolescent patients applying 1.5% ruxolitinib cream at any time; no patients had serious adverse events. There were no serious infections, malignancies, major adverse cardiovascular events, or thromboembolic events. Conclusions: Meaningful anti-inflammatory and antipruritic effects were demonstrated with 1.5% ruxolitinib cream in the subset of adolescent patients with AD, comparable with those observed in the overall study population; long-term, as-needed use maintained disease control and was well tolerated. Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03745638 (registered 19 November 2018) and NCT03745651 (registered 19 November 2018). [ABSTRACT FROM AUTHOR]

Secondary bacterial infections of common dermatoses such as atopic dermatitis, ectoparasitosis, and varicella zoster virus infections are frequent, with Staphylococcus aureus and Streptococcus pyogenes being the bacteria most involved. There are also Gram-negative infections secondary to common dermatoses such as foot dyshidrotic eczema and tinea pedis. Factors favoring secondary bacterial infections in atopic dermatitis, ectoparasitosis, and varicella zoster virus infections mainly include an epidermal barrier alteration as well as itch. Mite-bacteria interaction is also involved in scabies and some environmental factors can promote Gram-negative bacterial infections of the feet. Furthermore, the bacterial ecology of these superinfections may depend on the geographical origin of the patients, especially in ectoparasitosis. Bacterial superinfections can also have different clinical aspects depending on the underlying dermatoses. Subsequently, the choice of class, course, and duration of antibiotic treatment depends on the severity of the infection and the suspected bacteria, primarily targeting S. aureus. Prevention of these secondary bacterial infections depends first and foremost on the management of the underlying skin disorder. At the same time, educating the patient on maintaining good skin hygiene and reporting changes in the primary lesions is crucial. In the case of recurrent secondary infections, decolonization of S. aureus is deemed necessary, particularly in atopic dermatitis. [ABSTRACT FROM AUTHOR]

The article discusses the American Academy of Dermatology Annual Meeting that was held in San Diego, U.S. from March 8-12, 2024. Topics discussed include the efficacy and safety of different treatments for skin conditions like hidradenitis suppurativa and psoriasis. Attendees included experts such as Kimball AB, Papp KA, and Bissonnette R, who presented research findings on treatments like remibrutinib, lutikizumab, sonelokimab, ESK-001, and JNJ-77242113.

Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis. Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis. Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16. Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes. Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52. Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018). Plain Language Summary: Atopic dermatitis, or eczema, is a condition that causes painful itchy dry skin, which is burdensome for patients and has a negative impact on quality of life. These symptoms frequently lead to disruption of daily activities such as school and work, decreased self-confidence, social isolation, anxiety, depression, and sleep disturbance. Symptoms of atopic dermatitis, such as itch and sleep disturbance, can only be assessed by patients. Therefore, it is important to consider patients' perceptions of their symptoms and the related impact on their quality of life, especially when evaluating treatment benefits. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. In two clinical trials (Measure Up 1 and Measure Up 2), we investigated how treatment with upadacitinib (15-mg or 30-mg dose) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis would impact their symptoms and quality of life over a 1-year period. We measured changes over time in patients' assessments of itch, pain, other skin-related symptoms, sleep, daily activities, emotional state, mental health, and overall quality of life. Patients treated with upadacitinib experienced improvements in symptoms of atopic dermatitis and quality of life within the first 1–2 weeks of treatment. These improvements continued to steadily increase in the following weeks and lasted through 1 year of treatment. In conclusion, once-daily treatment with upadacitinib 15 or 30 mg led to early and lasting improvements in the well-being of patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD. Despite new targeted therapies, many patients with moderate-to-severe AD fail to achieve or sustain their individual treatment goals and/or may not be suitable for or tolerate these therapies. There remains a need for a novel, efficacious, well-tolerated therapeutic option that can deliver durable benefits across a heterogeneous AD patient population. Expression of OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], a prominent T-cell co-stimulatory molecule, and its ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] is increased in AD. As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD. [ABSTRACT FROM AUTHOR]

Therapeutic options for people with moderate or severe atopic dermatitis refractory to topical therapy have rapidly expanded in recent years. These new targeted immunomodulatory agents—biologics and Janus kinase (JAK) inhibitors—have each demonstrated high levels of efficacy and acceptable safety in mostly placebo-controlled clinical trials for atopic dermatitis, but there is no universally applicable algorithm to help choose between them for a given patient. Hence, patients and physicians should utilize shared decision making, discussing efficacy, safety, mode of delivery, monitoring, costs, speed of onset, and other factors to reach individualized treatment decisions. In this review, we try to aid shared decision making by summarizing the efficacy, safety, and monitoring of biologics and oral JAK inhibitors for adults with atopic dermatitis. Network meta-analyses suggest that higher doses of abrocitinib and upadacitinib are more effective than biologics. They also show that, among biologics, dupilumab is likely more effective than tralokinumab and lebrikizumab. Biologics are generally considered safer than JAK inhibitors, although concerns about JAK inhibitors are mainly extrapolated from older generation JAK inhibitors used in higher-risk populations. We also outline evidence and considerations for choosing and using systemic immunomodulatory treatments for special populations including pregnant individuals, those with human immunodeficiency virus (HIV), hepatitis B and C, end stage kidney disease, and older adults. [ABSTRACT FROM AUTHOR]

The skin is a physical and immunological barrier to the external environment. Its large surface area is colonized by diverse communities of microorganisms, including bacteria, viruses, fungi, and Demodex species mites. These microorganisms and their genetic material together create the skin microbiome. Physiologic and anatomic properties of skin sites create biogeographical habitats (dry, moist, and sebaceous) where distinct microbiota communities reside. Although, in general, the composition of these habitats is maintained from person to person, the skin microbiome of an individual also has unique microbial features. Dysbiosis occurs when the normal abundance, composition, or location of the microbiota is changed, most notably there is a decrease in flora diversity. Certain skin diseases, including atopic dermatitis, rosacea, and psoriasis are associated with cutaneous dysbiosis, and even disruption of the gut microbiota. Studies have shown that current treatments for these dermatologic conditions can alter/stabilize the skin microbiome, and there is emerging research detailing the impact of prebiotics, probiotics, and postbiotics on these conditions. Although clinical guidelines do not currently exist, clinical studies support the safety and possible benefits of using topical prebiotics and postbiotics and oral probiotics for a variety of skin conditions. Until such guidelines exist, utilizing carefully designed clinical studies to inform clinical practice is recommended. [ABSTRACT FROM AUTHOR]

Background: Ruxolitinib cream is the first topical Janus kinase (JAK) inhibitor approved in the United States (US) for the treatment of mild to moderate atopic dermatitis and nonsegmental vitiligo. A postmarketing study with oral tofacitinib, approved for rheumatoid arthritis, triggered class warnings for JAK inhibitors, including risk of serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis. Because ruxolitinib cream is indicated for inflammatory conditions, it is subject to the same warnings as oral JAK inhibitors in the US. Here, nearly 14,000 patient-years of postmarketing safety data from the first year following market approval of ruxolitinib cream were reviewed. Methods: The Incyte global safety database (21 September 2021–20 September 2022) and US FDA Adverse Event Reporting System (as of 30 September 2022) were queried for adverse event (AE) reports received for ruxolitinib cream. Results: The search identified 294 postmarketing individual case safety reports containing 589 events, including four serious AEs and no fatal AEs. AEs (i.e., any unfavorable sign, symptom, or disease) representing >2% of all events included application site pain (n = 16), atopic dermatitis (n = 15), skin irritation (n = 15), scratch (n = 14), and condition aggravated (n = 13). The four serious AEs were skin cancer (n = 2), pericarditis, and thrombocytopenia (both n = 1), none of which had sufficient information to assess possible relatedness to ruxolitinib cream. Serious AEs associated with the class warnings for JAK inhibitors were not reported. Conclusions: Postmarketing safety data from the year following approval suggest ruxolitinib cream is generally well tolerated, without significant systemic AEs, and with a low incidence of application site reactions. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is one of the most common inflammatory skin diseases among children and adults. Over the last 5 years, the armamentarium for the treatment of this disease, with both topical and systemic drugs, has increased. Treat-to-target is basically the concept where a treatment goal and a time frame for that goal is set at initiation of a new treatment, and if the goals are not achieved in time, treatment will be adjusted. In clinical trials, treatment targets are based on scoring systems for disease severity as recommended by the Harmonizing Outcome Measure for Eczema (HOME) initiative, with the primary endpoint being a reduction of at least 75% of the baseline Eczema Area and Severity Index (EASI) score (EASI-75). The question, however, is if these are useful targets in real-world settings and how this should be implemented in everyday clinical practice. In rheumatology, setting a measurable target and a time frame for an instigated therapy has been shown to lead to more efficient and successful treatment. For atopic dermatitis, the instruments recommended by HOME form the core outcome measures for the treat-to-target frameworks published to date, which are based on expert consensus and Delphi processes. Although atopic dermatitis patients have a high risk of co-morbidities, including physical, psychological and socioeconomic, instruments to measure the severity of co-morbidities have not been included in these existing frameworks. In order to apply a treat-to-target strategy that is meaningful for both the patient and the doctor, validated tools for the measurement of treatment effect on co-morbidities exist and should be included in a shared decision-making process with the individual patient when choosing which targets to aim for and what should be considered treatment success. An obvious limitation for the implementation of a treat-to-target strategy in the clinical setting with atopic dermatitis is that retrieving the data needed is very time consuming. This could to some degree be mitigated by the use of electronic applications in which patients could report their outcomes. [ABSTRACT FROM AUTHOR]

Hormonal and immunologic changes during pregnancy can contribute to the development of different dermatoses, the most common of which is atopic eruption of pregnancy (AEP). Of atopic dermatitis (AD) cases during pregnancy, 80% are new-onset presentations, while 20% represent recurrences or exacerbations of preexisting disease. Evidence on the effects of previous AD on fertility is limited. Different factors influence women's desire to conceive in this setting, and it has been hypothesized that barrier defects and systemic inflammation could contribute to biologic infertility, although more data are needed. Clinical practice suggests a tendency toward undertreatment in pregnant woman due to concerns about potential effects on obstetric and fetal outcomes. However, pregnant women should be offered adequate and safe treatments, preferably on an individual basis. The aim of this review was to summarize the evidence on disease course in pregnant women with AD and the challenges associated with its diagnosis and management. We also review the current evidence on the use of conventional and novel systemic therapies for AD in this population. [ABSTRACT FROM AUTHOR]

Background and Objective: AtopyReg® is a multicenter, prospective, observational, non-profit cohort study on moderate-to-severe atopic dermatitis in adults promoted in 2018 by the Italian Society of Dermatology and Venereology (SIDeMaST). We aimed to describe baseline demographics, disease characteristics, comorbidities, and therapeutic data of adult patients affected by moderate-to-severe atopic dermatitis. Methods: Patients were selected based on the following inclusion criteria: age ≥ 18 years; Eczema Area and Severity Index score ≥ 16 or localization in visible or sensitive areas (face, neck, hands, or genitalia), or a Numeric Rating Scale itch score ≥ 7 or a Numeric Rating Scale sleep loss score ≥ 7, or a Dermatology Life Quality Index score ≥ 10. Demographic and clinical data at baseline were recorded and analyzed. Results: A total of 1170 patients (male 51.1%; mean age: 44.7 years; range 18–90 years) were enrolled by 12 Italian Dermatology Units between January 2019 and November 2022. Skin lesions were eczematous in 83.2% of patients, the most involved site were the flexures (53.9%), face (50.9%), and neck (48.0%). Mean Eczema Area and Severity Index score was 22.3, mean Dermatology Life Quality Index value was 17.6, mean Patient Oriented Eczema Measure score was 13.1, and mean Numeric Rating Scale itch and sleep loss scores were 7.6 and 5.9, respectively. Previous systemic therapies were corticosteroids in 77.7% of patients, antihistamines in 50.3% of patients, and cyclosporine A in 42.6% of patients. Conclusions: This baseline data analysis deriving from AtopyReg® provides real-life evidence on patients with moderate-to-severe atopic dermatitis in Italy confirming the high burden of atopic dermatitis with a significant impact on patients' quality of life. [ABSTRACT FROM AUTHOR]

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. 6QcTdZHHiWG8xHjHtHEVo6 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) [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis. Objective: The aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial. Methods: A repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep. Results: The relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4–6, and 10 were associated with 0 days, 3–4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0–1, 4–5, and 10 were associated with 0–10%, 20–30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep. Conclusion: These results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity. Clinical Trial Registration: NCT03575871 Plain Language Summary: Atopic dermatitis (AD), also called atopic eczema, is a common skin disease that is associated with itch and reduced quality of life. Abrocitinib, a recently approved medicine for AD, was shown in clinical trials to improve itch, which is considered the most bothersome symptom to people with AD. Abrocitinib also improved sleep outcomes and work productivity in people with moderate or severe AD. It is unknown if improvement in itch can lead to improvement in sleep and work productivity. We analyzed data from the JADE MONO-2 study, which included 391 people who received treatment with abrocitinib or placebo for 12 weeks. We used mathematical modelling to study relationships between itch and sleep or work productivity. We also wanted to study if the improvements in itch and sleep with abrocitinib treatment had an impact on work productivity. We found that a relationship existed between itch, sleep disturbance, and work impairment; as itch improved, so too did sleep disturbance and work impairment. When people were treated with abrocitinib, they experienced relief from itch, which improved sleep, which in turn reduced work productivity loss. Larger and longer studies are needed to confirm these results. This analysis further informs the expectations of patients with moderate or severe AD as it relates to progression of symptom relief after treatment with abrocitinib. [ABSTRACT FROM AUTHOR]

Background: Two phase III trials, ECZTRA 1 and 2, confirmed the efficacy and safety of tralokinumab versus placebo in adults with moderate-to-severe atopic dermatitis (AD). To further explore the long-term efficacy of tralokinumab for AD, a pooled analysis of these trials was conducted. Methods: ECZTRA 1 and 2 patients (n = 1596 total) were randomized to tralokinumab 300 mg or placebo every 2 weeks (q2w) over 16 weeks. Patients achieving Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) and/or 75% improvement in the Eczema Area and Severity Index (EASI-75) at Week 16, were re-randomized to tralokinumab q2w, every 4 weeks (q4w), or placebo (tralokinumab withdrawal) for another 36 weeks. Patients not achieving the response criteria at Week 16 received open-label tralokinumab q2w plus optional topical corticosteroids (TCS). A pooled, prespecified analysis assessed the proportions of Week 16 responders that maintained IGA 0/1 and/or EASI-75 at Week 52. Pooled data from all patients initiated with tralokinumab, regardless of the response at Week 16 or dosing regimen received thereafter, were analyzed post hoc. Results: In patients who achieved the primary endpoints at Week 16, IGA 0/1 responses were maintained at Week 52 without rescue treatment (including TCS) by 55.9%, 42.4%, and 34.0% of patients re-randomized to tralokinumab q2w, q4w, or placebo (tralokinumab withdrawal), respectively, while EASI-75 responses were maintained by 57.3%, 50.4%, and 26.4%, respectively (prespecified analysis). In a post hoc analysis of all patients initiated with tralokinumab, response rates improved over time with continued tralokinumab treatment beyond Week 16 to Week 52 for EASI-50 (63.1–82.7%), EASI-75 (37.6–61.8%), EASI-90 (20.4–37.3%), and IGA 0/1 (23.0–36.2%). Conclusions: Tralokinumab treatment provides progressive and sustained improvement over 1 year in the extent and severity of AD in patients with moderate-to-severe AD. 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. Infographic: Plain Language Summary: Atopic dermatitis (AD) is a chronic inflammatory disease characterized by excessively dry and itchy skin, resulting in a considerable burden of disease. Patients with AD often require long-term treatment. Tralokinumab is an injectable antibody treatment that targets a protein called interleukin-13, which substantially contributes to the signs and symptoms of AD. In the ECZTRA 1 and 2 phase III clinical trials, funded by LEO Pharma A/S, adults with moderate-to-severe AD treated with tralokinumab every other week for 16 weeks showed significant improvement in disease extent and severity compared with patients receiving placebo. To further explore the long-term efficacy of tralokinumab for AD, we performed a new analysis combining the almost 1600 patients of ECZTRA 1 and 2. A large proportion of patients treated with tralokinumab who achieved clear or almost clear skin at Week 16 were able to maintain clear or almost clear skin at Week 52 with less frequent dosing (every 4 weeks). Additionally, combining all patients treated with tralokinumab, regardless of Week 16 response or dose frequency thereafter, showed that most patients achieved a significant reduction in disease extent and severity at Week 52. These results demonstrate that many tralokinumab-treated patients continue to improve beyond Week 16, and highlight that efficacy results at Week 16 may not be representative of the outcome of longer-term tralokinumab treatment. These findings may help health care providers better advise patients regarding when to modify treatment with tralokinumab. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory disease requiring efficacious and safe long-term therapy. Several new systemic treatments have recently been approved for use in patients with moderate to severe AD. However, head-to-head comparisons have not been conducted for all the currently available treatments for AD. Multiple network meta-analyses have compared efficacy of these different therapies during the initial 16-week treatment period, but not beyond week 16. Therefore, understanding the differences in key trial design and statistical methods is essential for evaluating long-term efficacy, making cross-trial comparisons, and informing treatment decisions. This focused narrative review provides an overview of data and trial methodology to guide clinicians in evaluating longer-term efficacy and safety of currently approved systemic treatments for patients with AD. We discuss important elements of longer-term trial designs and statistical analysis strategies that should be considered based on our experience as clinical trialists. In addition, a summary of key efficacy results of published, longer-term, phase III clinical trials of US Food and Drug Administration-approved, novel systemic treatments (i.e., dupilumab, tralokinumab, abrocitinib, and upadacitinib) is provided, including the design and data handling methods used. Long-term safety considerations and differences in the time-effect and safety profiles of various medications are also noted to help inform clinical decisions for individual patients. Overall, the findings of these trials support efficacy in long-term treatment with novel systemic agents for patients with AD. [ABSTRACT FROM AUTHOR]

Background: Janus kinase (JAK) inhibitors, including upadacitinib, have been recently approved for the treatment of moderate-severe atopic dermatitis (AD) and real-world data on upadacitinib effectiveness and safety are limited. This interim analysis aimed to assess effectiveness and safety of upadacitinib throughout 48 weeks of observation in a real-world adult AD population. Methods: This prospective study collected data on adult patients affected by moderate-to-severe AD and treated with upadacitinib at the dosage of either 15 mg or 30 mg daily based on the physician decision. Upadacitinib was prescribed in the context of a national compassionate use programme. In this interim analysis, within patient comparisons of continuous scores of different scales (namely Eczema Area and Severity Index [EASI], body surface area [BSA], Dermatology Life Quality Index [DLQI], Patient Oriented Eczema Measure [POEM], Numeric Rating Scale [NRS] subtests) were performed. The percentage of patients achieving EASI 75, EASI 90 and EASI 100 at Week 16, 32 and 48 was also evaluated. Results: One hundred and forty-six patients were included in the analysis. Upadacitinib 15 mg or 30 mg daily was prescribed as monotherapy in most cases (127/146, 87.0%). Upadacitinib was initially prescribed at the dosage of 30 mg daily in 118 of 146 (80.8%) patients and 15 mg daily in 28/146 (19.2%) patients. A significant improvement in the clinical signs and symptoms of AD was detected by Week 16 and throughout the study period. EASI 75, EASI 90 and EASI 100 responses were achieved by 87.6%, 69.1% and 44.3% at Week 48, associated with a sustained reduction in the mean values of all physician-reported (EASI and BSA) and patient-reported (Itch- Sleep- and Pain-NRS, DLQI, and POEM) disease severity outcomes, up to 48 weeks of treatment. Treatment response observed in 15 mg upadacitinib-treated patients was comparable with that detected in 30 mg upadacitinib-treated patients, revealing no statistical difference between the two patient sub-cohorts. Through the observation period, dose reduction or escalation was observed in 38/146 (26%) of treated cases. Overall, 26 of 146 (17.8%) patients experienced at least one adverse event (AE) during the treatment period. In total, 29 AEs were recorded and most of them were evaluated as mild to moderate, while in 4 cases the occurrence of AE led to drug discontinuation, for a total of 7/146 (4.8%) dropouts. Conclusion: This study provides strong evidence of a sustained response obtained by upadacitinib in AD patients, who had failed to respond to conventional or biological systemic agents, through 48 weeks of observation. Upadacitinib was also demonstrated to be advantageous in terms of flexibility in dose reduction or escalation as upadacitinib dose was shaped on clinical needs that, in a real-world setting, might frequently change. [ABSTRACT FROM AUTHOR]

Dupilumab is an interleukin (IL)-4/13 inhibitor approved by the US FDA for multiple atopic indications. It is well-known to have favorable efficacy and safety profiles; however, emerging reports of dupilumab-associated arthritis suggest an underrecognized potential adverse effect. In this article, we summarize the literature to date to better characterize this clinical phenomenon. Arthritic symptoms were most commonly peripheral, generalized, and symmetric. Onset was generally within 4 months following initiation of dupilumab, and most patients resolved fully after a matter of weeks following discontinuation. Mechanistic insights suggest that suppression of IL-4 may lead to increased activity of IL-17, a prominent cytokine in inflammatory arthritis. We propose a treatment algorithm that stratifies patients by severity, recommending that patients with more mild disease continue dupilumab and treat through symptoms, while patients with more severe disease discontinue dupilumab and consider switching to another class (e.g., Janus kinase inhibitors). Lastly, we discuss important ongoing questions that should be addressed in future studies. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, heterogeneous inflammatory skin disease that is associated with immense patient burden globally. There is increasing appreciation of disparities among patients identified as having skin of color (SOC), which often refers to patients of non-White race or non-European ancestry, but can broadly include individuals from a number of different racial, ethnic, ancestral, and skin pigmentation groups based on definition. In this narrative review, we discuss key terminology as it relates to AD across shades of skin, including modern definitions of 'race', 'ethnicity', and 'SOC'. We then synthesize the current literature describing disparities in AD prevalence, disease recognition, and burden alongside current data regarding genetic and immunologic findings across SOC populations. In the context of these findings, we highlight key concomitant social determinants of health, including environmental factors, socioeconomic status, and access to care, for which race often serves as a proxy for true biological and genetic differences. Finally, we discuss future efforts to shift to a more inclusive understanding of AD to encompass all shades of skin, to ensure equitable representation of diverse populations in high impact research, and intensify efforts to address the critical upstream factors driving observed disparities. [ABSTRACT FROM AUTHOR]

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. E91VSsKmsTg9JpbJbaReFk Video Abstract: Does dupilumab provide clinically meaningful responses in children 6 to 11 years old with severe atopic dermatitis? (MP4 99484 kb) [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common, heterogeneous, inflammatory skin disorder characterized by chronic or relapsing eczematous lesions with intense pruritus and discomfort. Affected patients often experience significant impairment in their quality of life, and the treatment of moderate-to-severe AD forms remains challenging. In the past few decades, increasing knowledge on the AD pathogenesis has driven the development of novel targeted therapies. Interleukin (IL)-13 plays a central and pleiotropic role in AD pathogenesis, contributing directly or indirectly to epidermal barrier disfunction, type-2 inflammation, dysbiosis, fibrosis, and itch response. For this reason, agents selectively targeting IL-13, such as lebrikizumab, emerged as a potential therapy for AD. This article reviews the current evidence about lebrikizumab in the management of AD. The phase II and phase III trials seem to corroborate efficacy of lebrikizumab in the treatment of moderate-to-severe AD, as shown by significant improvement of Eczema Area and Severity Index, body surface area, and pruritus scores. Also, lebrikizumab demonstrated favorable safety and tolerability profiles, with the majority of patients experiencing no significant adverse events. Lebrikizumab seems to be a promising emerging targeted biological agent for patients with moderate-to-severe AD. More data on the long-term efficacy and safety, head-to-head comparisons with other agents, and real-world evidence will help to clarify its place in therapy in AD. [ABSTRACT FROM AUTHOR]

Importance: The cancer risks associated with treatment with topical calcineurin inhibitors (TCIs) in patients with atopic dermatitis (AD) remain controversial, and limited evidence exists regarding the cancer risks among patients with AD treated with TCIs in Asian populations. Objectives: This study identified the association between TCI use and the risks of developing all cancers, lymphoma, skin cancers, and other cancers. Design: This study was a nationwide, population-based, retrospective cohort study. Setting: Taiwan's National Health Insurance Research Database. Participants: Patients diagnosed at least twice with ICD-9 code 691 or at least one time with ICD-9 codes 691 or 692.9 within 1 year between 1 January 2003 and 31 December 2010 were included and followed until 31 December 2018. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using the Cox proportional hazard ratio model. Exposures: Patients using tacrolimus or pimecrolimus were identified in the National Health Insurance Research Database and compared with patients using topical corticosteroids (TCSs). Main Outcomes and Measures: The main outcomes were hazard ratios (HRs) of cancer diagnoses and associated outcomes obtained from the Taiwan Cancer Registry database. Results: After propensity score (PS) matching, the final cohort included 195,925 patients with AD, including 39,185 who were initial TCI users and 156,740 who were TCS users. Propensity score matching was performed according to age, sex, index year, and Charlson Comorbidity Index using a ratio of 1:4. Except for leukemia, HR and 95% CI showed no significant associations between TCI use and the risk of developing all cancer, lymphoma, skin cancers, and other cancers. Sensitivity analysis showed that the lag time HRs for every cancer subtype continued to show no significant association between TCI use and cancer risk, except for leukemia. Conclusions and Relevance: Our study found no evidence to support an association between TCI use and the risks of almost all cancers compared with TCS use in patients with AD, but physicians should be aware of potentially higher risks of leukemia with TCI use. This study represents the first population-based study focused on the cancer risk of TCI use among patients with AD in an Asian population. [ABSTRACT FROM AUTHOR]

Background: Lebrikizumab is a monoclonal antibody that binds with high affinity to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. Objectives: To report integrated safety of lebrikizumab in adults and adolescents with moderate-to-severe atopic dermatitis from phase 2 and 3 studies. Methods: Five double-blind, randomized placebo-controlled studies; one randomized open-label study; one adolescent open-label, single-arm study; and one long-term safety study were summarized in two datasets: (1) placebo-controlled week 0–16 (All-PC Week 0–16) in patients who received lebrikizumab 250 mg every 2 weeks (LEBQ2W) versus placebo and (2) patients who received any dose of lebrikizumab at any time during the studies (All-LEB). Exposure-adjusted incidence rates (IR)/100 patient-years (PY) are provided. Results: A total of 1720 patients received lebrikizumab (1637.0 PY exposure). In All-PC Week 0–16, the frequency of treatment-emergent adverse events (TEAEs) was similar between treatment groups; most events were nonserious and mild or moderate in severity. The most frequently reported TEAEs were atopic dermatitis (placebo) and conjunctivitis (LEBQ2W). Frequencies of conjunctivitis cluster were 2.5% (placebo) and 8.5% (LEBQ2W), and all events were mild or moderate (All-LEB 10.6%, IR, 12.2). Frequencies of injection site reactions were 1.5% (placebo) and 2.6% (LEBQ2W; All-LEB 3.1%, IR, 3.3). Frequencies of adverse events leading to treatment discontinuation were 1.4% (placebo) and 2.3% (LEBQ2W; All-LEB 4.2%, IR, 4.5). Conclusion: The safety profile for lebrikizumab consisted of TEAEs that were mostly nonserious, mild or moderate in severity, and did not lead to treatment discontinuation. The safety profile was similar in both adults and adolescents. Clinicaltrials.gov: NCT02465606, NCT02340234, NCT03443024, NCT04146363, NCT04178967, NCT04250337, NCT04250350, NCT04392154 87Goioj2s3YFhSk64fjZWv Safety of lebrikizumab in adults and adolescents with moderate-to-severe atopic dermatitis: an integrated analysis of eight clinical trials (MP4 34165 KB) Plain Language Summary: Atopic dermatitis (AD) is a common chronic (persistent) skin disease that occurs in up to 7% of adults and approximately 20% of children. Lebrikizumab is a monoclonal antibody that goes against interleukin-13, which is overexpressed in patients with AD. Lebrikizumab is given by injection and is being studied to treat AD. It has been tested in several studies in both adults and adolescents (patients age ≥ 12 – < 18 years). In some of those studies, patients used lebrikizumab by itself, and in other studies patients used lebrikizumab in combination with low-to-moderate strength topical (rubbed on the skin) corticosteroid medicines. We examined the safety of lebrikizumab by combining the data from eight of those studies and analyzing the data in two datasets. The first dataset compared the safety of lebrikizumab 250 mg injected every 2 weeks with placebo (no drug in the injection) in four 16-week studies in which neither patient nor physician knew whether lebrikizumab or placebo was being injected. The second dataset included four additional studies and examined the safety of lebrikizumab in all patients receiving at least 1 injection of lebrikizumab at any dose. A total of 1720 patients took lebrikizumab. In the first dataset the frequency of adverse events was similar between lebrikizumab and placebo, and most events that did occur were mild or moderate in severity and were not serious. The most common adverse event in patients treated with placebo was atopic dermatitis, and in patients treated with lebrikizumab it was conjunctivitis. Frequencies of adverse events in the conjunctivitis cluster, which included a search for the terms of conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, and giant papillary conjunctivitis, were 2.5% in placebo and 8.5% in lebrikizumab, and all events were mild or moderate. Frequencies of injection site reactions were 1.5% in placebo and 2.6% in lebrikizumab, and frequencies of adverse events that led to patients stopping treatment were 1.4% in placebo and 2.3% in lebrikizumab. In the second dataset, the rate of these adverse events did not increase with longer duration of lebrikizumab. The safety profile for lebrikizumab consisted of adverse events that were mostly nonserious, mild or moderate in severity, and did not lead to stopping treatment. The safety profile was similar in both adults and adolescents. [ABSTRACT FROM AUTHOR]

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. Plain Language Summary: Atopic dermatitis (AD), also known as atopic eczema, is a skin disease that causes itchy and red skin patches. People can be diagnosed with severe and/or difficult-to-treat AD if their signs and symptoms of AD are extremely severe and their AD cannot be adequately treated by common medicines. Abrocitinib is a treatment that has been shown in clinical trials to improve the symptoms of AD. We analyzed data from the JADE COMPARE study, which included 837 people who were treated with abrocitinib, dupilumab (another treatment for AD), or placebo. Many of these people had severe symptoms when they entered the study. Some had AD signs and symptoms that did not improve after they took common medicines for AD. We studied how well abrocitinib worked in these people with severe and/or difficult-to-treat AD. We found that these people achieved clear skin and itch relief at week 16 after treatment with abrocitinib 200 mg compared with placebo (no drug control). Additionally, they achieved significant relief from itch faster with abrocitinib 200 mg compared with abrocitinib 100 mg, dupilumab, or placebo. People reported less severe AD and better quality of life after treatment with abrocitinib compared with placebo. Together, the findings of our study provide important evidence for healthcare providers as they determine a treatment plan for people with severe and/or difficult-to-treat AD. [ABSTRACT FROM AUTHOR]

Background: Topical treatments for atopic dermatitis (AD) used reactively often fail to achieve lasting disease control; many of these therapies are associated with safety concerns that limit long-term use. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD that has potential as a long-term maintenance therapy. Objective: The aim was to evaluate the long-term efficacy and safety of crisaborole once daily (QD) compared to vehicle QD as a maintenance therapy to reduce the incidence of flares in patients with AD who previously responded to crisaborole twice daily (BID). Methods: CrisADe CONTROL was a randomized, double-blind, vehicle-controlled, 52-week, phase III study of patients aged ≥ 3 months with mild-to-moderate AD involving ≥ 5% treatable body surface area. Eligible patients received crisaborole BID during an open-label run-in period of up to 8 weeks. Responders were randomly assigned in the double-blind maintenance period to receive either crisaborole QD or vehicle QD. Responders were defined as patients who achieved Investigator's Static Global Assessment (ISGA) success (ISGA score of 0 [clear] or 1 [almost clear] with a ≥ 2-grade improvement) and ≥ 50% improvement in Eczema Area and Severity Index total score (EASI-50) from baseline. Patients who experienced a flare (ISGA score ≥ 2) during the double-blind maintenance period switched to crisaborole BID for up to 12 weeks. During this period, patients were assessed every 4 weeks; if the flare resolved (ISGA score ≤ 1), patients resumed their assigned treatment. The primary endpoint was flare-free maintenance until onset of the first flare. Key secondary endpoints were number of flare-free days, number of flares, and maintenance of pruritus response until onset of the first flare. The incidence of treatment-emergent adverse events was also analyzed. Results: Overall, 497 patients entered the open-label run-in period with crisaborole BID, of which 270 patients were randomized into the 52-week double-blind maintenance period of the study. Of the 270 patients, 135 were randomly assigned to the crisaborole QD group and 135 were randomly assigned to the vehicle QD group. Median time of flare-free maintenance was longer for patients who received crisaborole versus vehicle (111 vs 30 days, respectively; p = 0.0034). The mean number of flare-free days was higher for patients who received crisaborole versus vehicle (234.0 vs 199.4 days, respectively; p = 0.0346). The mean number of flares was lower for patients who received crisaborole versus vehicle (0.95 vs 1.36, respectively; p = 0.0042). No clear trend was observed in maintenance of pruritus response between crisaborole- and vehicle-treated patients. Crisaborole was well tolerated, with no new or unexpected safety findings when used as maintenance treatment. Conclusions: Crisaborole QD was effective and well tolerated for long-term maintenance treatment and flare reduction in adult and pediatric patients with mild-to-moderate AD. Trial Registration: ClinicalTrials.gov, NCT04040192, 31 July 2019. Plain Language Summary: Atopic dermatitis (AD) is an immuno-inflammatory skin disease that can last a long time. It causes skin lesions and intense itching. Topical AD treatments used reactively often fail to control the disease over a long period of time. Many are associated with safety concerns that limit long-term use. Crisaborole ointment is a nonsteroidal treatment for the skin and is used to treat mild-to-moderate AD. Previous studies showed that using crisaborole twice daily was effective and had few side effects in patients with mild-to-moderate AD. This study evaluated how effective and safe long-term treatment with once-daily crisaborole was compared with an ointment with no drug (vehicle). The study included patients aged ≥ 3 months with mild-to-moderate AD whose AD improved after previous treatment with twice-daily crisaborole. This study was designed to investigate how much crisaborole reduced the incidence of AD flares over 52 weeks in these patients. The study included 270 patients whose AD had improved after treatment with twice-daily crisaborole. Of these patients, 135 were randomly assigned to receive crisaborole once a day and 135 to receive vehicle once a day. Patients who received crisaborole had a significantly longer time before experiencing AD flares than those who received vehicle. Crisaborole was well tolerated, and no new or unexpected side effects were found when used as a once-daily maintenance treatment for 52 weeks. These results indicate that once-daily treatment with crisaborole could be a potential long-term maintenance treatment option in children and adults with mild-to-moderate AD. [ABSTRACT FROM AUTHOR]

Climate change has a pervasive impact on health and is of clinical relevance to every organ system. Climate change-related factors impact the skin's capacity to maintain homeostasis, leading to a variety of cutaneous diseases. Stratospheric ozone depletion has led to increased risk of melanoma and keratinocyte carcinomas due to ultraviolet radiation exposure. Atopic dermatitis, psoriasis, pemphigus, acne vulgaris, melasma, and photoaging are all associated with rising levels of air pollution. Elevated temperatures due to global warming induce disruption of the skin microbiome, thereby impacting atopic dermatitis, acne vulgaris, and psoriasis, and high temperatures are associated with exacerbation of skin disease and increased risk of heat stroke. Extreme weather events due to climate change, including floods and wildfires, are of relevance to the dermatologist as these events are implicated in cutaneous injuries, skin infections, and acute worsening of inflammatory skin disorders. The health consequences as well as the economic and social burden of climate change fall most heavily on vulnerable and marginalized populations due to structural disparities. As dermatologists, understanding the interaction of climate change and skin health is essential to appropriately manage dermatologic disease and advocate for our patients. [ABSTRACT FROM AUTHOR]

Chronic eczematous eruptions of aging (CEEA) refers to a heterogenous group of longstanding, pruritic eczematous dermatoses with an unidentified etiology, or those which do not meet strict disease criteria. The literature has not yet established a single ubiquitous disease or term for these eruptions in adults over the age of 65 years. Instead, CEEA is attributed various names, including immunologic eruption of aging, and eruption of immunosenescence. Atopic dermatitis in the elderly, eczema in the elderly, and late- or adult-onset atopic dermatitis or eczema likely also fall under the umbrella of CEEA, given that older patients often do not meet strict criteria for atopic dermatitis. As a reflection of such terminological heterogeneity, CEEA does not have a standardized workup algorithm. This lack of uniformity can obscure the ability to study and understand appropriate treatments for this condition. Yet, as providers become increasingly aware of CEEA and more comfortable in making this diagnosis in older adults, it is necessary that dermatologists understand the safety and efficacy of common CEEA treatments in this population. Here, we discuss special considerations, challenges, and recommendations for treating older adults with CEEA with topical and systemic therapeutics. We provide an overview of therapeutic strategies and potential barriers to treatment and discuss the essential role of shared decision making when caring for this patient population. [ABSTRACT FROM AUTHOR]

Background: Adults aged ≥ 60 years are often underrepresented in atopic dermatitis (AD) clinical trials; age-related comorbidities may impact treatment efficacy and safety. Objective: The aim was to report dupilumab efficacy and safety in patients aged ≥ 60 years with moderate-to-severe AD. Methods: Data were pooled from four randomized, placebo-controlled dupilumab trials of patients with moderate-to-severe AD (LIBERTY AD SOLO 1 and 2, LIBERTY AD CAFÉ, and LIBERTY AD CHRONOS) and stratified by age (< 60 [N = 2261] and ≥ 60 [N = 183] years). Patients received dupilumab 300 mg every week (qw) or every 2 weeks (q2w), or placebo with/without topical corticosteroids. Post hoc efficacy at week 16 was examined using broad categorical and continuous assessments of skin lesions, symptoms, biomarkers, and quality of life. Safety was also assessed. Results: In the ≥ 60-year-old group at week 16, a greater proportion of dupilumab-treated patients achieved an Investigator's Global Assessment score of 0/1 (q2w: 44.4%; qw: 39.7%) and 75% improvement in Eczema Area and Severity Index (63.0%; 61.6%) versus placebo (7.1% and 14.3%, respectively; P < 0.0001). Type 2 inflammation biomarkers (immunoglobulin E and thymus and activation-regulated chemokine) were also significantly reduced in dupilumab- versus placebo-treated patients (P < 0.01). Results were similar in the < 60-year-old group. The exposure-adjusted incidences of adverse events in dupilumab-treated patients were generally similar to those receiving placebo, with numerically fewer treatment-emergent adverse events in the dupilumab-treated ≥ 60-year-old group versus placebo. Limitations: There were fewer patients in the ≥ 60-year-old group; post hoc analyses. Conclusion: Dupilumab improved AD signs and symptoms in patients aged ≥ 60 years; results were comparable to those in patients aged < 60 years. Safety was consistent with the known dupilumab safety profile. Trial Registration: ClinicalTrials.gov: NCT02277743, NCT02277769, NCT02755649, NCT02260986. DAhitXvUt5z-PjCq13QV7Z Does dupilumab benefit adults aged 60 years and older with moderate-to-severe atopic dermatitis?(MP4 20,787 KB) [ABSTRACT FROM AUTHOR]

Ruxolitinib cream 1.5% (OPZELURA™) is a topical formulation of ruxolitinib, a potent, selective inhibitor of Janus kinase (JAK)1 and JAK2. The targeting of these kinases is associated with therapeutic benefits in patients with atopic dermatitis (AD). In two identically designed, multinational, phase III studies in patients aged ≥ 12 years with mild to moderate AD, ruxolitinib cream 1.5% improved measures of disease severity, pruritus and sleep disturbance relative to vehicle cream when applied twice daily for 8 weeks. Disease severity was controlled for the next 44 weeks when applied as needed to active lesions. Ruxolitinib cream 1.5% was well tolerated in this patient population; its safety profile was similar to that of vehicle cream over the short term, with the types of treatment-emergent adverse events typical of those seen in the vehicle-controlled period over the longer term. Moreover, application site treatment-emergent adverse events indicative of skin tolerability issues (e.g. stinging/burning sensation) were infrequent and no safety findings suggestive of systemic JAK inhibition were identified. Although further longer-term data would be of use, ruxolitinib cream 1.5% provides an alternative to established topical agents (e.g. corticosteroids and calcineurin inhibitors) for the treatment of mild to moderate AD in adults and adolescents. Plain Language Summary: Atopic dermatitis (AD; also known as atopic eczema) is a chronic, relapsing, inflammatory skin disease that most commonly occurs in children but may also affect adults. Ruxolitinib cream 1.5% (OPZELURA™) is a topical therapy that inhibits Janus kinase (JAK)1 and JAK2, which are enzymes that can modify the inflammatory pathways involved in AD. It is approved in the USA for short-term and non-continuous longer-term treatment of mild to moderate AD in non-immunocompromised patients aged ≥ 12 years whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Patients experienced clearer skin and a reduction in itch and disturbed sleep when treated with ruxolitinib cream 1.5% twice daily compared with a non-medicated cream for 8 weeks. Moreover, clearer skin was maintained for a further 44 weeks when using the treatment as needed. The safety profile of ruxolitinib cream 1.5% was similar to that of the non-medicated cream, and stinging/burning sensations following application were infrequent. Thus, ruxolitinib cream 1.5% offers an alternative to established topical agents (e.g. corticosteroids and calcineurin inhibitors) for the treatment of adults and adolescents with mild to moderate AD. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral Janus kinase 1 inhibitor, provided significant itch relief by week 2 in patients with moderate-to-severe atopic dermatitis (AD) in the phase III JADE COMPARE trial. Objectives: This post-hoc analysis of JADE COMPARE aimed to further characterize itch response and determined whether early itch relief could predict subsequent improvements in AD severity. Methods: JADE COMPARE was a randomized, double-blind, double-dummy, placebo-controlled trial. Adult patients (aged ≥ 18 years) with moderate-to-severe AD were randomly assigned to receive oral abrocitinib 200 mg or 100 mg once daily, subcutaneous dupilumab 300 mg every other week (after a 600-mg loading dose), or placebo, plus medicated topical therapy for 16 weeks. Assessments were ≥ 4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) from days 2 to 15, Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA) response, and Dermatology Life Quality Index (DLQI) scores at week 12. Association between week 2 PP-NRS4 and efficacy at week 12 was evaluated by chi-squared tests. The predictive value of early response for later efficacy was assessed by area under the receiver operating characteristic curve. Results: As early as day 4 after treatment, a significantly greater proportion of patients achieved PP-NRS4 response with abrocitinib 200 mg (18.6%) versus dupilumab (5.6%; p < 0.001) and placebo (6.0%; p < 0.003). A similar trend was observed with abrocitinib at the 100-mg dose, with significantly greater PP-NRS4 response rates versus placebo as early as day 9. With both doses of abrocitinib, week 12 IGA 0/1, EASI-75, EASI-90, and DLQI 0/1 response rates were greater in week 2 PP-NRS4 responders than nonresponders; no differences were observed between week 2 PP-NRS4 responders and nonresponders in the dupilumab and placebo groups. Early improvement in PP-NRS at week 2 was associated with skin clearance at week 12 in abrocitinib-treated patients. Conclusions: Abrocitinib resulted in rapid relief from itch in patients with moderate-to-severe AD, with significant improvement in itch as early as day 4 after treatment with abrocitinib 200 mg compared with dupilumab and placebo. Abrocitinib-induced itch relief by week 2 was associated with subsequent improvements at week 12. [Video abstract available.] Trial registration: ClinicalTrials.gov identifier: NCT03720470. 2fQ_82bhGurT9XTD9WAh-8 Early itch response with abrocitinib is associated with later efficacy outcomes in patients withmoderate-to-severe atopic dermatitis: subgroup analysis of the randomized phase III JADE COMPARE trial (MP4 335,375kb) Plain Language Summary: An investigation into whether quick relief from itch with abrocitinib, a new medicine for atopic dermatitis, leads to later improvements in skin rash Atopic dermatitis (AD), also called atopic eczema, is a skin disease that affects people throughout their lives. About 10% of adults worldwide have AD. Itch is the most bothersome symptom reported by people with AD and scratching this itch can damage the skin, resulting in painful sores. It is unknown if relief from itch can influence other symptoms of AD. We analyzed data from the JADE COMPARE study, which included 837 people who received treatment with abrocitinib, dupilumab or placebo. We studied how fast itch relief occurred after people received these treatments. We also wanted to study if rapid itch relief was associated with improvement in other signs of AD later on with continued treatment. We found that as early as 4 days after treatment, abrocitinib 200 mg provided significant relief from itch compared with dupilumab or placebo. People who had rapid itch relief within 2 weeks of treatment with abrocitinib were more likely to have clear or almost clear skin and improved quality of life after 12 weeks of continued treatment with abrocitinib. Rapid itch relief did not appear to increase the likelihood of clear skin at week 12 in people who received dupilumab. Larger studies are needed to confirm this result. This study provides important evidence for physicians as they analyze itch relief and determine treatment options for people with AD. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis is a chronic inflammatory skin disease that can negatively impact work productivity and daily activities. Ruxolitinib cream, a Janus kinase inhibitor, demonstrated efficacy and safety in patients with atopic dermatitis in two phase III studies (TRuE-AD1 and TRuE-AD2). Objective: This post hoc analysis sought to describe the effects of ruxolitinib cream on work productivity and activity impairment from pooled data from the phase III studies, to estimate indirect costs due to atopic dermatitis, and to estimate the incremental cost savings with ruxolitinib cream versus vehicle cream. Methods: Patients in both studies were ≥ 12 years old with atopic dermatitis for ≥ 2 years, an Investigator's Global Assessment score of 2 or 3, and a 3–20% affected body surface area at baseline. Patients were randomized 2:2:1 to receive ruxolitinib cream (0.75% or 1.5%) or vehicle cream for 8 weeks. Patient self-reported productivity in the efficacy-evaluable population was assessed at weeks 2, 4, and 8 using the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem version 2.0. Statistical significance for the two doses versus vehicle was calculated using an analysis of covariance. Work Productivity and Activity Impairment overall work impairment scores were converted to a model of costs per employed patient due to lost productivity and incremental cost savings from ruxolitinib cream treatment using a human capital approach. Results: Of 1249 patients enrolled (median age, 32 years; female sex, 61.7%), 1208 were included in the efficacy-evaluable population. Patients applying 0.75% or 1.5% ruxolitinib cream had significant changes in overall work impairment (− 17.9% [0.75% strength] and − 15.0% [1.5% strength] vs − 5.7% for vehicle; p < 0.0001 for both) and daily activity impairment (− 20.6% [0.75% strength] and − 21.5% [1.5% strength] vs − 10.6% for vehicle; p < 0.0001 for both). These corresponded to estimated lost productivity costs in 2021 US dollars of $1313 (0.75% strength) and $1242 (1.5% strength) versus $2008 (vehicle) over the 8-week trial period. Compared with a patient receiving vehicle, incremental annual indirect cost savings were estimated to be $5302 with 0.75% ruxolitinib cream and $4228 with 1.5% ruxolitinib cream. Conclusions: Ruxolitinib cream therapy is associated with improved work productivity and daily activity compared with vehicle and is estimated to reduce the indirect cost burden on the patient. Clinical trial registration: ClinicalTrials.gov identifiers: NCT03745638 (registered 19 November, 2018) and NCT03745651 (registered 19 November, 2018) [ABSTRACT FROM AUTHOR]

The article provides an overview of the recent World Congress of Dermatology held in Singapore with the theme "Dermatology Beyond Borders.It mentions the notable studies discussed at the congress include the results of clinical trials for novel treatments for psoriasis, atopic dermatitis, and alopecia areata, showcasing advancements in dermatological research and potential treatment options.

Background: Numerous systematic reviews and meta-analyses have examined the effects of probiotics used perinatally on prevention or treatment of atopic disease in infants and children. However, to date, no review has examined randomized controlled trials of Lactobacillus rhamnosus, specifically, administered both prenatally and postnatally and its effect over a long period of time. Objective: The objective was to determine if L. rhamnosus either used solely or in conjunction with other probiotics demonstrates a long-term preventive effect on atopic disease in pediatric patients when used perinatally. Methods: A systematic review was undertaken to identify those studies where L. rhamnosus was used (either solely or in conjunction with other probiotics). The following databases were searched from the year 2000 through December 8, 2021: PubMed, Cochrane Reviews and Cochrane Central Database of Controlled Trials; systematic reviews were hand searched to identify randomized controlled trials (RCTs). Meta-analytic statistical techniques were then employed. Evaluation of the incidence of atopic eczema was also examined longitudinally based on timeframe. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessments were employed to determine the quality of the evidence. Results: Eleven randomized controlled trials were identified which examined L. rhamnosus in its effect on atopy. Risk of bias was low on the majority of the domains assessed. Meta-analysis of the timeframes ≤ 2 years (RR 0.60, 95% CI 0.47–0.75; p < 0.00001) and 6–7 years (RR 0.62, 95% CI 0.50–0.75; p < 0.00001) demonstrated statistically significant reductions in atopic eczema with use of L. rhamnosus. For the 4 to 5-year (RR 0.74, 95% CI 0.55–1.00; p = 0.05) and 10–11-year (RR 0.68, 95% CI 0.37–1.27; p = 0.23) timeframes there was no statistically significant reduction. GRADE assessment for each timeframe was considered moderate in two, owing to high attrition rates in all of the studies, and low in two due to imprecision. Conclusion: Based on the meta-analysis and GRADE assessments, the use of L. rhamnosus with or without other probiotics appears to have a positive effect in reducing the incidence of atopic eczema in pediatric patients at least out to 7 years. Attrition rates temper these findings. [ABSTRACT FROM AUTHOR]

Background: There is a clear link between skin disease and psychological factors and this relationship works both ways: skin diseases can cause psychological distress and psychological issues can worsen skin disease. There are a number of therapies that approach this problem from the psychological side and may be useful, especially as adjunctive therapies in select patients. Objective: The aim of this review was to determine the efficacy of various psychological therapies and mind–body techniques in the management of common dermatologic diseases in individuals of all ages. Methods: A systematic review of PubMed, Elsevier, and Wiley was performed for studies investigating psychological and mind–body interventions in the management of various skin diseases. Both physical and non-physical treatment outcomes were considered. Studies were evaluated for both risk of bias and overall quality of evidence. Results: A total of 40 articles studying unique sets of dermatological patients receiving psychological therapies or mind–body interventions were identified. Of the 40 included articles encompassing 3112 patients, 18 investigated these interventions in psoriasis management while 15 focused on atopic dermatitis. The remaining studies investigated vitiligo (2), pruritus (2), acne vulgaris (2), and acne excoriée (1). Conclusions: Based on the analysis of included studies and an assessment of their quality of evidence, the most promising interventions are cognitive behavioral therapy, mindfulness-based interventions, and habit reversal therapy. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin condition that can have tremendous impact on quality of life for affected children and adults. First-line therapy for acute management of AD includes topical therapies such as corticosteroids, calcineurin inhibitors, and, more recently, the phosphodiesterase inhibitor crisaborole. Topical agents have remained the mainstay therapy for decades; however, there has been a longstanding need for topical therapies with high efficacy and low risk of adverse effects with long-term use. Given the ongoing advances in understanding the pathogenesis of AD, there are novel targets for pharmacological intervention. We are now in an unprecedented time with more than 40 topical treatments in the pipeline for AD in addition to many developments and treatments on the horizon. This review summarizes selected therapeutic topical agents in later phases of development that target various aspects in the pathogenesis of AD such as Janus kinase inhibition (ruxolitinib and delgocitinib), phosphodiesterase-4 inhibition (roflumilast and difamilast), aryl hydrocarbon modulation (tapinarof), and modulation of the microbiome. We also review novel targeted therapies that are in early phase clinical trials, including AMTX-100, BEN-2293, and PRN473. Preliminary findings on efficacy and tolerability of most of these agents are promising, but further studies are warranted to evaluate the long-term safety and efficacy of these novel agents against the current standard of care. [ABSTRACT FROM AUTHOR]

Janus kinase (JAK) inhibitors are immunomodulatory agents with broad potential for use within dermatology. However, the US Food and Drug Administration has recently placed additional warning labels on JAK inhibitors given concern for an increased risk of major adverse cardiovascular events, malignancy, venous thromboembolism, and mortality. Here, we summarize recent efficacy and safety data of multiple JAK inhibitors including tofacitinib, upadacitinib, baricitinib, and abrocitinib. JAK inhibitors have high efficacy in treating psoriatic arthritis and atopic dermatitis, but carry an increased risk of venous thromboembolism and cardiovascular events relative to other approved treatments. Here, we provide current considerations on balancing the benefits of JAK inhibitors with potentially serious, but low-absolute risk, safety concerns. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of tralokinumab, a fully human monoclonal antibody that specifically neutralizes interleukin-13, plus topical corticosteroids (TCS) as needed were evaluated over 32 weeks in the phase III ECZTRA 3 trial. Significantly more tralokinumab- versus placebo-treated patients achieved the primary endpoints of Investigator's Global Assessment (IGA) score of 0/1 and 75% improvement in Eczema Area and Severity Index (EASI-75) and all confirmatory endpoints at Week 16. Objective: This post hoc analysis investigated the impact of tralokinumab plus TCS on atopic dermatitis (AD) severity, symptoms, and health-related quality of life (QoL) over the entire 32-week treatment period of ECZTRA 3, including all patients initiated on tralokinumab irrespective of the response achieved at Week 16. Methods: Patients were randomized 2:1 to receive subcutaneous tralokinumab 300 mg or placebo every 2 weeks (q2w) with TCS as needed for an initial 16 weeks. At Week 16, patients who achieved the clinical response criteria (IGA 0/1 and/or EASI-75) with tralokinumab were re-randomized 1:1 to tralokinumab q2w or every 4 weeks (q4w), with TCS as needed, for another 16 weeks. Patients not achieving the clinical response criteria with tralokinumab received tralokinumab q2w plus TCS from Week 16. All patients randomized to tralokinumab in the initial treatment period were pooled for this analysis, irrespective of response at Week 16 or dosing regimen beyond Week 16. Results: Continued tralokinumab (q2w, N = 164; q4w, N = 69) plus TCS treatment provided progressive improvements from Week 16 onwards in AD signs, with 70.2% (177/252) of patients achieving EASI-75 and 50.4% (127/252) achieving EASI-90 at Week 32. Improvements in patient-reported outcomes were observed within the first few weeks of tralokinumab q2w plus TCS treatment and were sustained throughout the 32-week period. At Week 32, patients initiated on tralokinumab q2w plus TCS achieved a relative improvement versus baseline of 70.8% (standard error (SE), 2.4) in eczema-related sleep interference numeric rating scale (NRS) and 66.8% (SE, 3.1) in Dermatology Life Quality Index (DLQI). Mean TCS use during Weeks 16–32 ranged from 9.2 to 13.6 g (SE, 1.2–2.0) q2w. Most patients (89.9% (222/247)) initiated on tralokinumab q2w plus TCS achieved a meaningful improvement in at least one of the three disease domains, including AD signs (EASI-50), symptoms (pruritus NRS improvement ≥ 3), and QoL (DLQI improvement ≥ 4) at Week 16. Of patients initiated on tralokinumab q2w plus TCS, 53.4% (132/247) achieved a clinically meaningful improvement in all three domains at Week 16 (vs. placebo, 28.5% (35/123); p < 0.001). Conclusions: Continued tralokinumab treatment plus TCS as needed provides progressive and sustained improvements in AD signs, symptoms, and health-related QoL over 32 weeks. Clinical trial registration: NCT03363854; study start date: 22 February 2018; primary completion date: 8 March 2019; study completion date: 26 September 2019. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is characterized by a heterogenous longitudinal course with varying severity, flares, and persistence. However, AD course is not routinely assessed in clinical practice or controlled trials. Our objective was to review the longitudinal course of AD in children and adults and discuss implications for routine practice and clinical trials. We conducted a focused review of the published literature, including retrospective, prospective, and interventional studies, clinical trials, and consensus guidelines. Estimates of AD persistence varied widely across studies but suggested that AD can indeed persist through childhood and into adulthood. Predictors of persistence are broad and include both disease-intrinsic and disease-extrinsic (i.e., environmental) factors. In real-world practice, most individuals with AD experience fluctuations in the signs and symptoms over time and do not experience persistent clearance of skin lesions. Clinical trials use mainly static measurements that do not take into account fluctuations in course, which may confound treatment effects. The heterogenous temporal pattern of AD can be incorporated into routine practice to better set expectations and offer a realistic prognosis. AD course should be routinely incorporated into clinical decision making. Future studies are needed to develop a standardized approach to AD assessment and treatment that includes longitudinal course. [ABSTRACT FROM AUTHOR]

Background: Moderate‐to‐severe atopic dermatitis (AD) often requires long-term management with systemic therapies. Objective: Our objective was to report the safety and efficacy of dupilumab treatment up to 4 years in adults with moderate-to-severe AD and efficacy in a subgroup of patients who transitioned from dupilumab once-weekly (qw) to administration every other week (q2w). Methods: This interim analysis of the open-label extension study (NCT01949311) evaluated dupilumab 300 mg qw or q2w in adults previously enrolled in dupilumab trials for moderate-to-severe AD. Patients switched from qw to q2w following protocol amendment. The primary outcome was safety; efficacy was also assessed. Results: Of 2677 patients enrolled and treated, 352 (13.1%) completed week 204 (end of efficacy assessments) and 202 (7.5%) completed safety follow-up through week 244. Self-reported compliance was 98.1%. Dupilumab's safety profile was consistent with previous reports. Common treatment-emergent adverse events (≥5%) included nasopharyngitis, AD, upper respiratory tract infection, oral herpes, conjunctivitis, injection-site reaction, and headache. At week 204, mean ± standard deviation (SD) Eczema Area and Severity Index was 2.46 ± 3.98, and mean percent change from parent study baseline (PSBL) was −91.07%; mean ± SD Pruritus Numerical Rating Scale score was 2.10 ± 1.83, and mean percent change from PSBL was −68.74%. Efficacy was maintained in patients (n = 226) who transitioned from qw to q2w dosing. Limitations of this study included its open-label design, the lack of control arm, and smaller subsets of patients at later timepoints and receiving the approved q2w regimen. Conclusion: These results support dupilumab as continuous long-term treatment for adults with moderate-to-severe AD; efficacy was sustained following transition from qw to q2w dosing. Trial Registration ClinicalTrials.gov: NCT01949311. Plain Language Summary: Atopic dermatitis is a chronic skin disease associated with inflamed skin and intense itching. People with moderate-to-severe atopic dermatitis often need long-term treatment, but many available treatments do not have demonstrated long-term safety data. In multiple clinical trials, dupilumab treatment resulted in significant improvements in signs and symptoms of atopic dermatitis. This study examined the safety and efficacy of up to 4 years of dupilumab treatment in adults with moderate-to-severe atopic dermatitis, and whether dupilumab continued to be effective in patients who switched from receiving treatment each week to treatment every other week. To address these questions, we collected data from adults who received 300 milligrams of dupilumab every week or every other week. In this study, safety findings were consistent with the known dupilumab safety profile. Patients' signs and symptoms were evaluated before and during treatment with evaluation tools including the Eczema Area and Severity Index (EASI), which indicates the extent and severity of disease, and the Pruritus Numerical Rating Scale (NRS), which indicates the intensity of itching. Reductions of 91% in EASI scores and 69% in Pruritus NRS scores showed that the improvement in signs and symptoms persisted for 204 weeks (almost 4 years) of treatment, and these effects were sustained following the switch from weekly treatment to the approved every other week treatment with dupilumab. The safety and efficacy data presented here support the use of dupilumab as a continuous, long-term treatment for up to 4 years for adults with moderate-to-severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Baricitinib (Olumiant®) is an oral small molecule inhibitor of Janus kinase (JAK)1 and JAK2, which have been implicated in the pathogenesis of atopic dermatitis (AD). In phase III studies in adults with moderate to severe AD who were inadequately controlled with topical corticosteroids (TCS) or systemic treatments (e.g. ciclosporin), or for whom these therapies were not advisable, baricitinib, alone or in combination with TCS, achieved significant and/or clinically relevant improvements in multiple measures of disease severity, pruritus, skin pain, sleep disturbance and health-related quality of life (HR-QOL) over 16 weeks. Benefit onset was rapid, with efficacy generally sustained over the longer term (treatment duration ≤ 68 weeks). In this patient population, the safety profile of baricitinib was consistent with that established in the moderate to severe rheumatoid arthritis (RA) population. Although further longer-term data would be beneficial, current evidence indicates that baricitinib, alone or in combination with TCS, provides an oral alternative to subcutaneous biologics for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. Plain Language Summary: A better understanding of the multiple factors that cause atopic dermatitis (AD; a chronic, relapsing, inflammatory skin disease often known as eczema) has led to the development of novel therapies that target various inflammatory pathways involved in the disease process. Baricitinib (Olumiant®), a Janus kinase (JAK)1 and JAK2 inhibitor that targets inflammatory pathways in AD, is a once-daily oral treatment approved in the EU for moderate to severe AD in adults who are candidates for systemic therapy. In such patients, baricitinib, alone or in combination with topical corticosteroids, improved disease severity, pruritus, skin pain, sleep disturbance and health-related quality of life compared with placebo over 16 weeks. Benefit onset was rapid and generally sustained over the longer term (treatment duration ≤ 68 weeks). The safety profile of baricitinib in patients with moderate to severe AD is consistent with that seen in adults with moderate to severe rheumatoid arthritis treated with the drug. Thus, baricitinib provides a convenient oral alternative to subcutaneous biologics for the treatment of moderate to severe AD. [ABSTRACT FROM AUTHOR]

Background: For adolescent patients (aged ≥ 12 to < 18 years) with uncontrolled moderate-to-severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo, with an acceptable safety profile. However, long-term data on the approved dose regimens of dupilumab in adolescents with AD are lacking. Objectives: This open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in adolescents with moderate-to-severe AD who had participated in dupilumab parent trials. Methods: Patients enrolled under the original study protocol received subcutaneous dupilumab according to a weight-based regimen (2 or 4 mg/kg every week). Following protocol amendment, patients were switched to subcutaneous dupilumab 300 mg every 4 weeks (q4w) irrespective of weight, and newly enrolled patients were started on dupilumab 300 mg q4w. Patients with an inadequate clinical response (Investigator's Global Assessment [IGA] score of 0/1 was not reached) to the q4w regimen could be uptitrated to the approved dupilumab dose regimens of 200 or 300 mg every 2 weeks (body weight < 60 or ≥ 60 kg, respectively). Patients whose IGA score of 0/1 was maintained continuously for a 12-week period after week 40 were discontinued from dupilumab, monitored for relapse, and re-initiated on dupilumab if required. Results: Data for 294 patients (mean age 14.7 years) were analyzed, 102 (34.7%) of whom had completed the 52-week visit at the database lock. The dupilumab long-term safety profile was comparable to that seen in adults and consistent with the known safety profile. Most treatment-emergent adverse events were mild/moderate. By week 52, 42.7% of patients had an IGA score of 0/1 (clear/almost clear), and 93.1%, 81.2%, and 56.4%, respectively, had at least a 50%, 75%, or 90% improvement in Eczema Area and Severity Index (EASI). Most (70.9%) patients required uptitration to the approved dupilumab dose regimen. The proportions of uptitrated patients with an IGA score of 0/1 or 75% improvement in EASI increased over time, reaching 35.7% and 51.9%, respectively, 48 weeks after the first uptitration visit. By week 52, 29.4% of patients had clear/almost clear skin sustained for 12 weeks and had stopped medication; 56.7% relapsed and were subsequently re-initiated on treatment, with a mean time to re-initiation of 17.5 (± standard deviation 17.3) weeks. Conclusions: Consistent with results seen with short-term treatment, long-term treatment with dupilumab showed an acceptable safety profile while providing incremental clinical benefit with continued treatment over time. The high proportion of patients who needed uptitration because of inadequate response to q4w dosing supports the q2w dose regimen as optimal for this age group. Finally, the majority of patients who stopped medication after having clear/almost clear skin sustained over 12 weeks experienced disease recurrence, suggesting the need for continued dupilumab dosing to maintain efficacy. Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454, NCT02407756, NCT03054428, and NCT03050151. Infographic: EYru5bYjcUouUcQrkiC3DM Video abstract: What is the long-term safety and efficacy profile in adolescents with moderate-to-severe atopic dermatitis treated with the approved dupilumab dose regimen? (MP4 40,966 KB) Plain Language Summary: Atopic dermatitis, or eczema, is a common chronic skin disease that can cause intense and persistent itching and rashes. Atopic dermatitis remains a problem for many adolescent patients, even if they use a number of different treatments. Dupilumab is a newer treatment for atopic dermatitis. In short-term clinical studies, dupilumab improved the disease with acceptable safety. In this study, adolescents with moderate-to-severe atopic dermatitis who had completed one of the short-term studies continued dupilumab treatment for 1 year. The patients started treatment with dupilumab once every 4 weeks. But if their atopic dermatitis did not improve sufficiently, they were given dupilumab every 2 weeks. Through a year of treatment, there were no unexpected side effects. The side effects that did occur were mild or moderate in severity and in most cases did not lead to interruption of treatment. Almost half of the patients achieved skin that was clear or almost clear of atopic dermatitis during the study. But their atopic dermatitis often returned if they stopped being treated, and about half of them needed to start treatment again. Most patients needed to be treated every 2 weeks. The positive effects of dupilumab generally increased the longer patients were treated. [ABSTRACT FROM AUTHOR]

Background: Ruxolitinib cream is a topical formulation of ruxolitinib, an inhibitor of Janus kinase 1 and Janus kinase 2. Objective: We aimed to determine the safety, tolerability, and bioavailability of 1.5% ruxolitinib cream under maximum-use conditions in patients with atopic dermatitis. Efficacy was evaluated as an exploratory objective. Methods: Eligible patients aged ≥ 12–65 years with atopic dermatitis, an Investigator's Global Assessment score ≥ 2, and ≥ 25% affected body surface area were enrolled in an open-label, maximum-use phase I study conducted in the USA and Canada. Patients applied 1.5% ruxolitinib cream twice daily to lesions identified at baseline for the first 28 days and continued use only on active lesions for an additional 28 days (extension period). Safety was assessed by frequency, duration, and severity of treatment-emergent adverse events. Plasma concentrations of ruxolitinib and pharmacokinetic parameters were assessed as secondary endpoints. Results: Overall, 41 patients (median age, 17 years; 51% male) were enrolled and 37 (90.2%) entered the extension period, all of whom completed the study. Treatment-emergent adverse events were reported in 13 patients (31.7%). Treatment-related adverse events were reported in four patients (9.8%). The mean (standard deviation) steady-state plasma concentration was 104 (309) nM during the first 28 days, well below the half-maximal inhibitory concentration of Janus kinase-mediated myelosuppression in the bone marrow (281 nM), and decreased further during the extension period. Higher plasma concentrations were detected in a few patients who were treated for a very high affected body surface area. At day 56, 94.6% of patients achieved ≥ 75% improvement in the Eczema Area and Severity Index. Conclusions: Under maximum-use conditions, ruxolitinib cream was generally well tolerated, with approximately one-third of patients experiencing treatment-emergent adverse events and few treatment-related adverse events. The mean steady-state plasma concentration of ruxolitinib was well below the level expected to affect bone marrow production of blood cells, with a small number of patients exhibiting higher plasma concentrations. In addition, ruxolitinib cream showed a high level of efficacy in patients with atopic dermatitis involving ≥ 25% affected body surface area. ClinicalTrials.gov Identifier: NCT03920852. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of messenger RNA coronavirus disease 2019 (COVID-19) vaccines in patients with atopic dermatitis (AD) is yet to be delineated. It remains largely unknown how AD-related immunosuppressive medications affect the development of vaccine-induced immunity. Objective: We aimed to evaluate the prevalence of the BNT162b2 messenger RNA vaccine among patients with AD and to assess its effectiveness in protecting against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19-associated hospitalization, and mortality. A specific analysis additionally examined whether AD-related immunosuppressive drugs influenced the effectiveness of the vaccine. Methods: A population-based cohort study was performed using the database of Clalit Heath Services, Israel, to follow adult patients with AD. Multivariate Cox and logistic regression analyses were utilized to calculate the adjusted hazard ratio (HR) and odds ratio (OR) of the incident outcomes. Results: As of 26 June, 2021, 58,582 (75.4%) out of 77,682 adult patients with AD completed two BNT162b2 vaccine doses in Israel. Adulthood-onset AD (adjusted OR, 1.34; 95% CI 1.28–1.40; p < 0.001) and moderate-to-severe AD (adjusted OR, 1.13; 95% CI 1.05–1.21; p = 0.001) predicted an increased vaccination rate. Vaccinated patients with AD demonstrated a significantly decreased risk of SARS-CoV-2 infection (adjusted HR, 0.20; 95% CI 0.16–0.26; p < 0.001), COVID-19-associated hospitalization (adjusted HR, 0.08; 95% CI 0.04–0.18; p < 0.001), and COVID-19-associated mortality (adjusted HR, 0.04; 95% CI 0.01–0.20; p < 0.001). Exposure to immunosuppressive drugs (n = 597; 0.8% of patients) did not impair the protection against SARS-CoV-2 infection after vaccination (adjusted HR, 0.95; 95% CI 0.13–6.81; p = 0.958). Conclusions: In patients with AD, COVID-19 vaccination is highly effective for a wide range of COVID-19-related outcomes. Immunosuppressive drugs did not impair the effectiveness of the vaccine in preventing SARS-CoV-2 infection in this retrospective analysis. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that serum 25-hydroxyvitamin D (25(OH)D) may be associated with atopic dermatitis (AD), and that vitamin D (VD) supplementation may decrease AD severity. Objective: The aim of this study was to investigate the association between serum 25(OH)D level and AD, and the effect of VD supplementation on AD severity, while providing stratified analyses based on latitude and region. Methods: A systematic review was performed on all published studies in MEDLINE, Embase, and Cochrane Library databases that analyzed effects of serum 25(OH)D and VD supplementation on AD. Results: This systematic review and meta-analysis includes 20 studies with 1882 cases of AD. We found significantly lower 25(OH)D levels in AD patients compared with healthy controls (HC) (p < 0.001), significantly lower 25(OH)D levels in severe AD compared with both mild and moderate AD (p < 0.001), and VD supplementation improved AD symptoms (p < 0.001). Limitations: Factors like seasonal and environmental changes, sunlight exposure, and cultural practices may confound the relationship between serum 25(OH)D and AD severity. There are limited randomized controlled trials that assess this association. Conclusion: Overall, lower serum 25(OH)D is associated with more severe AD, and VD supplementation may help lower AD severity. Further research is needed to confirm the presence and direction of causality of the relationship between VD and AD pathogenesis. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target" which appeared in the previous issue of the periodical.

Diet has long been understood to have an intricate association with atopic dermatitis, although much remains unelucidated. Skin barrier dysfunction with dysbiosis and consequent impairment of immune tolerance likely underly the pathogenesis of coincident atopic dermatitis and food allergy. There is a wide range of possible skin reactions to food, complicating the diagnosis and understanding of food allergies. Many patients, parents, and providers incorrectly suspect diet as causative of atopic dermatitis symptoms and many have tried elimination diets. This frequently leads to inaccurate labeling of food allergies, contributing to a dangerous spiral of inappropriate testing, referrals, and dietary changes, while neglecting established atopic dermatitis treatment essentials. Alternatively, certain dietary supplements or the introduction of certain foods may be beneficial for atopic dermatitis management or prevention. Greater consensus on the role of diet among providers of patients with atopic dermatitis is strongly encouraged to improve the management of atopic dermatitis. [ABSTRACT FROM AUTHOR]

The recent advent of numerous clinical trials for the treatment of moderate-to-severe atopic dermatitis has led to new and emerging therapeutic options for this chronic inflammatory skin disease. With this rapid development has come a lack of consistency in study designs, trial conduct, and statistical analyses. Healthcare providers are challenged to interpret how variations in study parameters may influence clinical trial results. Based on literature review and our experience as clinical trialists, we compiled a list of 22 key study parameters of contemporary clinical trials in moderate-to-severe atopic dermatitis and ranked the top study parameters that may have a significant effect on efficacy results. The top parameters included study comparators, rules for rescue treatment, washout periods for topical and systemic treatments, inclusion criteria such as disease severity by Eczema Area and Severity Index and/or Investigator Global Assessment scores, and the duration of the screening period. We describe considerations for these key parameters, with a focus on between-parameter interactions and effect on efficacy results. This may serve to inform the interpretation of atopic dermatitis clinical trials and raise the profile of the need to harmonize the clinical trial design. Plain Language Summary: Atopic dermatitis (AD) is a skin disease characterized by red, itchy skin that is highly burdensome for patients. Patients with moderate-to-severe disease have large, inflamed skin areas with frequent itching. Recently, the number of clinical trials for drugs that treat moderate-to-severe AD has rapidly increased, with differences in how these trials are designed. There is a need for healthcare providers examining results from different clinical trials to understand how trial design factors might influence study outcomes. In this article, we identify key trial design factors that impact study outcomes, detail how these factors can impact clinical trial results, and explore how these factors interact with one another to affect study outcomes. The five most important design factors, as determined via author surveys, were study comparators (a placebo and/or another drug to which the drug being studied is compared); the rules for the use of rescue treatment (a form of treatment given if an enrolled participant has uncontrolled AD symptoms); washout periods (the time before the trial when previous treatments are stopped to allow them to be cleared from a patient's system); inclusion criteria (that determine which participants are included); and the length of the screening period (the time when patients are assessed to determine if they qualify for participation). By understanding how these key trial design factors impact on study outcomes, healthcare providers may be equipped to better interpret different AD clinical trials. This work also emphasizes the value of harmonizing the AD clinical trial design. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis is a chronic, inflammatory condition causing a substantial burden to patients and caregivers. SHR0302 is an oral, highly selective, Janus kinase 1 inhibitor under investigation for inflammatory skin diseases. Objective: The aim of this study was to investigate the efficacy and safety of SHR0302 in Chinese patients with moderate to severe atopic dermatitis. Design and Setting: A randomized, double-blind, placebo-controlled, multicenter, phase II trial was conducted in China between October 2019 and August 2020. Participants: Patients (n = 105) aged 18–75 years with moderate to severe dermatitis and nonresponsive or intolerant to topical or conventional systemic treatments were included. Interventions: Patients were randomly assigned in a ratio of 1:1:1 to receive SHR0302 4 mg once daily, SHR0302 8 mg once daily, or placebo for 12 weeks. Main Outcome Measures: The primary efficacy endpoint was the proportion of patients achieving Investigator's Global Assessment (IGA) response (IGA of 0 [clear] or 1 [almost clear] with improvement of ≥2 grades) at week 12. Secondary efficacy assessments included Eczema Area and Severity Index (EASI) and pruritus Numerical Rating Scale (NRS) scores. Results: At week 12, IGA response was achieved in nine patients (25.7%; 90% confidence interval [CI] 13.6–37.9%; p = 0.022) in the SHR0302 4 mg group, 19 patients (54.3%; 90% CI 40.4–68.1%; p < 0.001) in the SHR0302 8 mg group, and two patients (5.7%; 90% CI 0.0–12.2%) in the placebo group. EASI75 was achieved in 51.4% (p = 0.013), 74.3% (p < 0.001), and 22.9% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively, while an NRS ≥3-point improvement occurred in 65.7% (p < 0.001), 74.3% (p < 0.001), and 22.9% of patients, respectively. Treatment-emergent adverse events were reported in 60.0%, 68.6%, and 51.4% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively. The adverse events were mild in most cases. Three serious adverse events were reported, all being worsening of atopic dermatitis. No serious infection was reported. Conclusions and Relevance: Oral SHR0302 was effective and well tolerated in Chinese adult patients with moderate to severe atopic dermatitis. Trial Registration: ClinicalTrials.gov identifier: NCT04162899; URL: https://clinicaltrials.gov/. Date first registered: 14 November 2019. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a common inflammatory skin disease that can affect both children and adults. It is a chronic disease with recurrent, highly pruritic eczematous lesions. Topical treatment with anti-inflammatory agents is the mainstay of treatment for atopic dermatitis, either in a reactive or proactive approach according to severity of the disease and always in combination with daily application of an emollient cream. Several studies have shown that proactive therapy with either topical corticosteroids or topical calcineurin inhibitors is significantly superior at reducing the number of flares and increasing the interval between flares compared with reactive therapy in patients with moderate and severe disease. The risk of side effects is considered low, and there seem to be no extra economic costs related to this treatment approach. Proactive therapy is an advisable treatment option for patients with moderate and severe atopic dermatitis to gain prolonged disease control; however, long-term safety data and data on when to stop do not yet exist. [ABSTRACT FROM AUTHOR]