Practical Management of the JAK1 Inhibitor Abrocitinib for Atopic Dermatitis in Clinical Practice: Special Safety Considerations.

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

Emollient application from birth to prevent eczema in high-risk children: the BEEP RCT.

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

Eczema is a troublesome itchy skin condition affecting 1 in 5 children and 1 in 10 UK adults. There is no cure and affected children are more likely to develop food allergies. We wanted to see if we could prevent eczema by protecting the skin of babies at higher risk of developing eczema (with an immediate relative with eczema, asthma or hay fever) with moisturisers used to treat dry skin. Previous research suggested that protecting the skin barrier might also prevent food allergy. One thousand three hundred and ninety-four families took part in a study; half of them were asked to apply moisturiser every day to their newborn baby for the first year and half to look after their baby's skin in the normal way. At the age of 2 years, we did not see any difference in how common eczema was between the two groups: 23% had eczema in the moisturiser group and 25% in the normal care group. It did not matter how we defined eczema ­ whether examined by a researcher or parent report. We did not find any differences in related conditions like asthma or hay fever either. We found that children using moisturisers had seen their doctor slightly more often for mild skin infections. There was a hint that food allergy might have been increased in the moisturiser group, but there was not enough data to be sure. We followed up the children to age 5 years, but we still did not find any benefits from using moisturisers in early life. Since this study, other similar research has been done using newer types of moisturisers, but their results are the same. This study shows that using daily moisturisers on healthy babies with a high risk of eczema does not prevent eczema. It is one less thing for busy families to worry about.

Ruxolitinib Cream in Adolescents/Adults with Atopic Dermatitis Meeting Severity Thresholds for Systemic Therapy: Exploratory Analysis of Pooled Results from Two Phase 3 Studies.

INTRODUCTION: Standard therapy for patients with mild to moderate atopic dermatitis (AD) typically includes topical therapies; however, patients with more extensive AD and/or AD refractory to topical therapy may benefit from systemic treatment. Ruxolitinib cream monotherapy has demonstrated superior antipruritic and anti-inflammatory effects versus vehicle in patients with mild to moderate AD, and long-term disease control with as-needed use. Here, efficacy/safety of 1.5% ruxolitinib cream through 52 weeks was assessed in a subset of patients with moderate and/or more extensive disease. METHODS: This post hoc analysis of TRuE-AD1/TRuE-AD2 included patients who, at baseline, had Investigator's Global Assessment (IGA) score of 3, Eczema Area and Severity Index (EASI) ≥ 16, and affected body surface area (BSA) ≥ 10% (higher severity of disease threshold subgroup). Disease control and safety were assessed. RESULTS: Of 1249 patients in the overall population, 78 (6.2%) met all higher severity of disease threshold criteria (continuous-use vehicle-controlled period: 1.5% ruxolitinib cream, n = 32; vehicle, n = 13); 28 and 4 of these patients, respectively, continued as-needed 1.5% ruxolitinib cream during the long-term safety (LTS) period. At week 8 (continuous-use), IGA-treatment success (IGA 0/1, with ≥ 2-grade improvement from baseline) was achieved by 19/32 (59.4%) patients applying 1.5% ruxolitinib cream versus no patients applying vehicle. In the LTS period, those achieving clear/almost clear skin increased from 19/28 patients (67.9%; continuous-use: week 8) to 18/23 patients (78.3%; as-needed use: week 52) in patients applying ruxolitinib cream from day 1. Ruxolitinib cream was well tolerated, with few application site reactions, regardless of disease severity threshold. Efficacy and safety results were similar to the overall study population. CONCLUSION: Patients with AD who meet standard disease severity eligibility criteria for systemic therapy may achieve IGA-treatment success with clear/almost clear skin with continuous-use ruxolitinib cream, and maintain long term-disease control with as-needed ruxolitinib cream monotherapy. TRIAL REGISTRATION NUMBER: NCT03745638/NCT03745651.

Atopic dermatitis (AD) is a skin condition that causes itchy, dry, and inflamed skin. For many people AD is controlled with medication that is applied to the skin. However, for some people medication that is taken orally or injected (i.e., systemic treatment) may be needed. Systemic treatment can sometimes be challenging. Doctors use a variety of tools to measure AD severity and apply standard criteria to help determine if a person should receive systemic treatment. In the TRuE-AD1/TRuE-AD2 clinical trials, itch and inflammation improved in people with mild to moderate AD after they applied ruxolitinib cream twice daily for 8 weeks. When people then applied ruxolitinib cream to areas of AD only when it was needed for another 44 weeks, ruxolitinib cream provided long-term control of their AD. The aim of this analysis was to assess disease control with ruxolitinib cream in people with AD severe enough to meet the standard criteria indicating a need for systemic treatment. In this group, the majority had clear or almost clear skin after applying ruxolitinib cream twice daily for 8 weeks. After 44 weeks of as-needed application of ruxolitinib cream, most people still had clear or almost clear skin. In this group of people who may have otherwise needed treatment with systemic therapy, ruxolitinib cream twice daily for 8 weeks and then as-needed was generally well tolerated. These results show that as-needed ruxolitinib cream may provide long-term control of AD in people who may otherwise have needed systemic therapy.

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.

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).

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. 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).

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

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

Efficacy, Safety, and Long-Term Disease Control of Ruxolitinib Cream Among Adolescents with Atopic Dermatitis: Pooled Results from Two Randomized Phase 3 Studies.

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).

Dupilumab Safety and Efficacy up to 1 Year in Children Aged 6 Months to 5 Years with Atopic Dermatitis: Results from a Phase 3 Open-Label Extension Study.

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).

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. What is the long-term safety and efficacy profile in young children with moderate-to-severeatopic dermatitis treated with dupilumab?

Treatment satisfaction in adults with atopic dermatitis: a cross-sectional, population-based study examining patient and physician perspectives in the US.

Studies examining the real-world treatment satisfaction in adults with atopic dermatitis (AD) and the physicians who treat adults with AD are scarce. We sought to characterize treatment satisfaction of adults with AD and physicians' perceived patient satisfaction with AD treatment. We performed a cross-sectional study of adults > = 18 years of age (modified AD UK Working Party Criteria, age onset < = 18 [N = 767]) with AD and a parallel-physician survey among allergists/immunologists [N = 148], dermatologists [N = 149] and primary care medicine [N = 104]. Logistic regression models were used to examine factors associated with patient treatment satisfaction (PTS) or physician-perceived patient treatment satisfaction (pPTS). Factors associated with increased PTS included female, older age, and receiving a written eczema action plan (EAP). Severe AD, itch, pain, and insomnia, greater impact on partner relationships, feeling not adequately informed about AD causes, and being separated, never married, or living with a partner was associated with less PTS. From the physician's perspective, mild AD and development of EAP was associated with increase pPTS, whereas being in practice longer was associated with less pPTS. Limitations include the potential for misclassification of AD and the inability to match AD patients to individual physicians. Recognizing which factors are associated with treatment satisfaction can help inform counseling and decision-making strategies, including the use of an eczema action plan, and support patient-physician outcomes alignment.

Upadacitinib Rapidly Improves Patient-Reported Outcomes in Atopic Dermatitis: 16-Week Results from Phase 3 Clinical Trials (Measure Up 1 and 2).

INTRODUCTION: Atopic dermatitis (AD) is characterized by intense itch and other symptoms that negatively impact quality of life (QoL). This study evaluates the effect of upadacitinib (an oral selective Janus kinase inhibitor) monotherapy on patient-reported outcomes (PROs) among adults and adolescents with moderate-to-severe AD over 16 weeks. METHODS: This integrated analysis of the double-blind, placebo-controlled periods of phase 3 monotherapy clinical trials Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) assessed itch (Worst Pruritus Numerical Rating Scale [WP-NRS] and SCORing Atopic Dermatitis [SCORAD]), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient-Oriented Eczema Measure), sleep (AD Impact Scale [ADerm-IS] and SCORAD), daily activities and emotional state (ADerm-IS), QoL (Dermatology Life Quality Index [DLQI] and Children's DLQI), mental health (Hospital Anxiety and Depression Scale), and patient impressions (Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment). RESULTS: Data from 1683 patients (upadacitinib 15 mg, n = 557; upadacitinib 30 mg, n = 567; placebo, n = 559) were analyzed. A greater proportion of patients receiving upadacitinib versus placebo experienced improvements in itch (≥ 4-point improvement on WP-NRS) by week 1 (upadacitinib 15 mg, 11.2%; upadacitinib 30 mg, 17.7%; placebo, 0.5%; P < 0.001), with response rates sustained through week 16 (upadacitinib 15 mg, 47.1%; upadacitinib 30 mg, 59.8%; placebo, 10.4%; P < 0.001). Improvements were similar for PROs assessing skin pain/symptoms, sleep, daily activities, QoL, emotional state, mental health, and patient impressions of disease severity and treatment. Responses generally improved rapidly (within 1-2 weeks), increased through weeks 4-6, and were maintained through week 16. CONCLUSIONS: Once-daily oral upadacitinib monotherapy improved response rates across PROs compared with placebo. Upadacitinib therapy resulted in rapid, sustained improvements in PROs measuring symptom burden and QoL in adults and adolescents with moderate-to-severe AD. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT03569293 and NCT03607422.

Atopic dermatitis, or eczema, is characterized by itchy, dry, inflamed skin. These symptoms often make it difficult for patients to get adequate sleep. Patients with atopic dermatitis may also experience anxiety, depression, reduced self-confidence, social isolation, disruption to daily activities like school and work, and decreased quality of life. Many atopic dermatitis symptoms, including itch and psychological impact, are difficult for doctors to assess. Thus, it is important to consider patients' descriptions of their symptoms and quality of life, particularly when assessing treatment benefit. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. We investigated how upadacitinib (15 mg or 30 mg) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis in the Measure Up 1 and 2 clinical trials impacts their symptoms and quality of life over a 16-week period. We compared changes in patient-reported itch, pain, sleep, daily activities, emotional state, mental health, and overall quality of life among patients in the clinical trials who received upadacitinib with those in the same studies who received a dummy (placebo) treatment. Upadacitinib improved patient-reported symptoms and quality of life early in the clinical trials, often within the first 1­2 weeks. The extent of the improvements increased through weeks 4­6 of treatment and lasted through week 16. Patients who received upadacitinib reported greater improvements in symptoms and quality of life than did patients who received placebo. Upadacitinib treatment resulted in rapid and lasting improvements in the well-being of patients with atopic dermatitis.

Lebrikizumab Provides Rapid Clinical Responses Across All Eczema Area and Severity Index Body Regions and Clinical Signs in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) affects multiple areas of the body, some of which may be more refractory to treatment. We evaluated improvements in the Eczema Area and Severity Index (EASI) by body region and clinical signs for each body region in lebrikizumab-treated patients with moderate-to-severe AD. METHODS: ADvocate 1 and ADvocate 2 compared lebrikizumab 250 mg as monotherapy every 2 weeks versus placebo for 16 weeks. Efficacy measures included EASI, which rates the extent and severity of four clinical signs (erythema, edema/papulation, excoriation, lichenification) in four body regions (head/neck, upper extremities, trunk, lower extremities). Analyses are post hoc. RESULTS: Mean baseline EASI, body region EASI subscores, and the severity of clinical signs were consistent across both studies (EASI ranging from 16.0 to 72.0). At week 16 in both studies, patients treated with lebrikizumab showed significantly greater percent improvement in EASI across all body regions versus placebo (p ≤ 0.001), with improvements as early as week 2. In ADvocate 1, all clinical signs significantly improved across all body regions at week 16 with lebrikizumab (51.4-71.6% improvement) versus placebo (23.1-43.5%, p ≤ 0.001), with significant improvements as early as week 2 for all signs. Significant improvements for all clinical signs at week 16 were also seen in ADvocate 2 for lebrikizumab (53.5-75.6%) versus placebo (28.5-41.2%, p ≤ 0.001) and as early as week 2 for all body regions and signs except head/neck erythema and lower extremity erythema, edema/papulation, and lichenification, which showed significant improvement by week 4. CONCLUSIONS: Lebrikizumab as monotherapy consistently and rapidly reduced the extent of involvement and severity of AD in all EASI clinical signs and body regions, including the head and neck region and clinical sign of lichenification, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ADvocate 1 (NCT04146363) and ADvocate 2 (NCT04178967).

Measuring Signs of Atopic Dermatitis in Clinical Practice: A HOME-CP Consensus Statement.

Importance: Outcome measurement is an essential component of value-based health care and can aid patient care, quality improvement, and clinical effectiveness evidence generation. The Harmonising Outcome Measures for Eczema Clinical Practice initiative aims to identify a list of validated, feasible, outcome measurement instruments recommended to measure atopic dermatitis (AD) in the clinical practice setting. The clinical practice set is a list of instruments that clinicians can pick and choose from to suit their needs in the context of clinical care. Objective: To recommend instruments to measure clinical signs of AD in clinical practice. Evidence Review: Following the predefined roadmap, a mixed methods design was implemented and incorporated systematic reviews and qualitative consensus methods. Previous systematic reviews identified few clinical signs instruments with sufficient validation for recommendation. An updated systematic review evaluating the validity of clinical signs instruments informed an international meeting to reach consensus on recommended instruments to measure AD clinical signs in clinical practice. Consensus was defined as less than 30% disagreement. An in-person consensus exercise was held in Montreal, Canada, on October 16, 2022. The 34 attendees included patient and patient advocate research partners, health care professionals, researchers, methodologists, and industry representatives. Findings: The updated systematic review found that the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis, and objective Scoring Atopic Dermatitis were the only instruments that demonstrated sufficient performance in all assessed measurement properties. The modified EASI and Signs Global Assessment × Body Surface Area instruments were also recommended. The EASI, Validated Investigator Global Assessment, and Investigator's Global Assessment multiplied by or measured concurrently with a body surface area measure achieved consensus in criteria and were adopted. Conclusions and Relevance: This consensus statement by the Harmonising Outcome Measures for Eczema initiative suggests that when assessing and documenting clinical signs of AD, there are several valid and feasible instruments that can best fit a clinician's specific practice needs. These instruments should improve and standardize the documentation of signs severity, help determine the effect of treatment, facilitate the generation of clinical effectiveness evidence, and enhance the implementation of value-based health care.

Ruxolitinib cream monotherapy demonstrates rapid improvement in the extent and signs of mild to moderate atopic dermatitis across head and neck and other anatomic regions in adolescents and adults: pooled results from 2 phase 3 studies.

Purpose: Ruxolitinib (selective Janus kinase [JAK] 1 and JAK2 inhibitor) cream demonstrated efficacy and safety in patients with atopic dermatitis (AD) in the phase 3 TRuE-AD studies. In TRuE-AD1/TRuE-AD2 (NCT03745638/NCT03745651), adults and adolescents with mild to moderate AD were randomized to apply twice-daily ruxolitinib cream or vehicle for eight weeks. Here, we evaluated the efficacy and tolerability of ruxolitinib cream by anatomic region, focusing on head/neck (HN) lesions that are typically difficult to manage and disproportionately affect quality of life (QoL).Materials and methods: Eczema Area and Severity Index (EASI) responses in anatomic regions were evaluated in the pooled population (N = 1208) and among patients with baseline HN involvement (n = 663). Itch, Investigator's Global Assessment (IGA), QoL, and application site tolerability were also assessed.Results: By Week 2 (earliest assessment), ruxolitinib cream application resulted in significant improvements across all EASI anatomic region subscores and AD signs versus vehicle, with further improvements through Week 8. Significantly more patients with HN involvement who applied ruxolitinib cream versus vehicle achieved clinically meaningful improvements in itch, IGA, and QoL. Application site reactions with ruxolitinib cream were infrequent (<3%), including in patients with HN involvement.Conclusions: These results support the use of ruxolitinib cream for AD treatment across all anatomic regions, including HN.

Dupilumab treatment improves signs, symptoms, quality of life, and work productivity in patients with atopic hand and foot dermatitis: Results from a phase 3, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Despite high disease burden, systemic treatment options for patients with atopic hand and/or foot dermatitis (H/F AD) are limited. OBJECTIVES: To evaluate efficacy and safety of dupilumab in H/F AD using specific instruments for assessing disease severity on hands and feet. METHODS: In this multicenter phase 3 trial, adults and adolescents with moderate-to-severe H/F AD were randomized to dupilumab monotherapy (regimen approved for generalized AD), or matched placebo. The primary endpoint was proportion of patients achieving Hand and Foot Investigator's Global Assessment score 0 or 1 at week 16. Secondary prespecified endpoints assessed the severity and extent of signs, symptom intensity (itch, pain), quality of life, and sleep. RESULTS: A total of 133 patients (adults = 106, adolescents = 27) were randomized to dupilumab (n = 67) or placebo (n = 66). At week 16, significantly more patients receiving dupilumab (n = 27) than placebo (n = 11) achieved Hand and Foot Investigator's Global Assessment score 0 or 1 (40.3% vs 16.7%; P = .003). All other prespecified endpoints were met. Safety was consistent with the known AD dupilumab profile. LIMITATIONS: Short-term, 16-week treatment period. CONCLUSION: Dupilumab monotherapy resulted in significant improvements across different domains of H/F AD with acceptable safety, supporting dupilumab as a systemic treatment approach for this often difficult to treat condition.

Real-World Effectiveness of Dupilumab in Adult and Adolescent Patients with Atopic Dermatitis: 2-Year Interim Data from the PROSE Registry.

INTRODUCTION: There is a scarcity of data beyond 1 year for the use of dupilumab to treat atopic dermatitis (AD) in a real-world setting. This study aimed to evaluate the 2-year effectiveness of dupilumab among adult and pediatric patients with moderate-to-severe AD included in a real-world, longitudinal database study. METHODS: PROSE is an ongoing, prospective, observational, multi-center registry in the USA and Canada, designed to collect real-world data from patients aged ≥ 12 years with moderate-to-severe AD who initiate dupilumab in accordance with country-specific prescribing information. Assessments include body surface area affected by AD (BSA), Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), Pruritus Numerical Rating Scale (P-NRS), Patient-Oriented Eczema Measure (POEM), Patient Global Assessment of Disease (PGAD) questionnaire score, and occurrence of adverse events (AEs). RESULTS: Of 764 patients who enrolled in PROSE, 632 (83%) remained in the study at the time of this interim analysis. Improvements were observed at the first post-baseline clinic visit (approximately 3 months) in the clinician-assessed measures (mean BSA and EASI scores); improvements were sustained throughout the 2-year period covered in the present study. Consistent and sustained improvements were also observed over the 2-year period in the patient-reported measures of P-NRS, POEM, and DLQI, and in the proportion of patients reporting "very good/excellent" in answer to the question in the PGAD questionnaire: "Considering all the ways in which your eczema affects you, indicate how well you are doing". Dupilumab treatment was well tolerated, with safety findings consistent with those previously reported in studies of dupilumab for the treatment of AD. CONCLUSIONS: In the real-world PROSE registry, patients with moderate-to-severe AD experienced sustained improvement in disease control, symptoms, and quality of life up to 2 years after initiating dupilumab treatment. Safety data were consistent with the known safety profile of dupilumab. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03428646. Video abstract (MP4 20,717 kb).

Atopic dermatitis (AD) is a long-term disease that affects the skin of patients, causing rash, inflammation, and intense itching, all leading to profound negative effects on their quality of life. In short-term studies, dupilumab has been shown to improve the signs and symptoms of AD, and to improve patients' quality of life. However, there is currently little information about the effectiveness of dupilumab when patients use it over the long term in the real world. This study used data from the ongoing PROSE registry, which is collecting information on 764 adults and adolescents (aged ≥ 12 years) with moderate-to-severe AD who are using dupilumab in the real world; patients were allowed to use other AD treatments and could even stop using dupilumab. Most patients (83%) were evaluated after 2 years of treatment. The study looked at how physicians judged changes over time in the severity of patients' AD. Importantly, it also used measures to allow patients themselves to report how they felt treatment affected their AD, the amount of itch they experienced, and their quality of life. Improvements in the severity of AD were already seen at 3 months, and they were maintained over the 2-year period. Patients also reported consistent and sustained improvements in their AD symptoms and quality of life during the 2 years of treatment. This analysis shows that patients with AD who began dupilumab treatment can have sustained long-term improvements.

Summary of Research: An Anti-OX40 Antibody to Treat Moderate-to-Severe Atopic Dermatitis: A Multicentre, Double-Blind, Placebo-Controlled Phase 2b Study.

This is a summary of the original article "An Anti-OX40 Antibody to Treat Moderate-to-Severe Atopic Dermatitis: a Multicentre, Double-blind, Placebo-Controlled Phase 2b Study". Atopic dermatitis (AD) is an inflammatory skin disease caused by a complex interplay of genetic factors, alterations to the skin microenvironment, and immune dysregulation, including T cells that have become uncontrolled. Rocatinlimab is an investigational agent that blocks OX40, a receptor on activated T cells that has an important role in inflammatory conditions such as AD. This summary of research provides an overview of a previously published article on the results of a phase 2b study of patients with moderate-to-severe AD who were treated with different doses of rocatinlimab or placebo and followed for up to 56 weeks. Rocatinlimab significantly improved the symptoms of AD and was well tolerated. The most common adverse events were fever, nasopharyngitis, and chills. This study supports rocatinlimab as a potentially safe and effective treatment for moderate-to-severe AD.