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Additional long-term treatments are needed for moderate-to-severe atopic dermatitis (AD). An ongoing, open-label, 5-year extension trial, ECZTEND (NCT03587805), assesses tralokinumab plus optional topical corticosteroids in participants from previous tralokinumab parent trials (PTs) with moderate-to-severe AD.To evaluate the safety and efficacy of up to 2 years tralokinumab treatment in a post hoc interim analysis.Safety analyses included adults from completed PTs enrolled in ECZTEND, regardless of tralokinumab exposure duration. Efficacy analyses included adult participants treated with tralokinumab in ECZTEND for ≥1 year and subgroup analyses of those on tralokinumab for 2 years (1 year from PT, 1 year in ECZTEND). Primary end point was the number of adverse events with additional efficacy end points.Participants on tralokinumab had an exposure-adjusted rate of 237.8 adverse events/100 patient-years' exposure (N = 1174) in the safety analysis set. Exposure-adjusted incidence rates of common adverse events were comparable to PTs, although at lower rates. With 2 years of tralokinumab, improvements in extent and severity of AD were sustained, with Eczema Area and Severity Index (EASI-75) in 82.5% of participants (N = 345).Possible selection bias; no placebo arm; some participants experienced treatment gaps between PTs and ECZTEND.Over 2 years, tralokinumab was well tolerated and maintained long-term control of AD signs and symptoms.

We carried out a critical appraisal of the literature to assess whether Janus kinase inhibitors are an effective treatment for palmoplantar pustulosis, a rare and debilitating form of psoraisis. Our appraisal identified case reports and case series of 16 patients who have been treated to good effect with tofacitinib, indicating this may be a promising therapeutic option. However, routine use of janus kinase inhibitors cannot be recommended outside the context of a clinical trial given the current low-quality of evidence available and the uncertain safety profile of Janus kinase inhibitors.

Background The European Prospective Observational Study in Patients Eligible for Systemic Therapy for Atopic Dermatitis (EUROSTAD) is an ongoing observational study aiming to describe characteristics of patients with atopic dermatitis (AD) treated with systemic therapy over time and the management of their disease in a real-world setting. Methods Data from patients enrolled in EUROSTAD between March 2017 and April 2019 were analyzed for systemic therapy use and treatment change over 12 months. Results 288 patients reported taking systemic medications; 42.7% received cyclosporine, 35.3% dupilumab, 28.1% methotrexate, 25.4% oral corticosteroids, 6.8% azathioprine, 6.1% injectable corticosteroids, and 3.4% mycophenolate. The median duration of treatment was 1.1 months for oral systemic corticosteroids, 3.2 months for injectable corticosteroids, 4.8 months for cyclosporine, 7.3 months for methotrexate, and 14.9 months for dupilumab. The most frequent reasons for stopping treatment included lack of efficacy, patient decision, adverse events, and disease well controlled. Conclusion The 12-month interim EUROSTAD study analysis highlights the current trends and outcomes of systemic treatments for moderate-to-severe AD. Among all systemic treatments for AD, dupilumab was the least likely to be discontinued, whereas cyclosporine and corticosteroids, whilst effective, were primarily limited to episodic flare management consistent with treatment guidelines.

Inconsistent criteria are used to identify patients with atopic dermatitis (AD) who are candidates for systemic therapy and assess their response to systemic therapy. This may lead to undertreatment and treatment dissatisfaction. A treat-to-target (T2T) framework was previously proposed to guide systemic treatment decisions in patients with moderate-to-severe AD.1 While patient representatives were included in the T2T consensus voting process, no patient or caregiver stakeholders were included in the development of the T2T recommendations. Additionally, a recent analysis of the cross-sectional, 28-country MEASURE-AD study suggests that the treatment targets in the T2T criteria may be insufficient to ensure optimal treatment outcomes.2 To develop optimized and practical criteria for identifying patients who should receive systemic therapy, including definitions of treatment goals, treatment failure and disease severity. An executive steering committee (ESC) of seven international experts was formed in January 2021 to provide insights and perspectives on how to optimize the identification of patients who would most benefit from systemic therapy for AD. After discussing the gaps and needs in current AD management, the ESC agreed that there was a lack of evidence on patients’ treatment goals, needs, and expectations. The ESC, therefore, initiated a global, ethically and culturally diverse patient research study (N = 88) to collect these insights. Subsequently, nine regional sub-committees (SCs) were created to gain clinical perspectives from different regions worldwide (covering the USA and Puerto Rico, Latin America, Western Europe and Canada, Eastern Europe and Russia, the Middle East, Asia, and Australia and New Zealand). Overall, 87 experts from 44 countries contributed to the initiative, and 46 virtual ESC and SC meetings took place to discuss how to improve the lives of patients with AD. A virtual secure platform allowed discussions and contributions to continue outside these meetings. In April 2022, all experts rated their agreement with a series of recommendations regarding the identification and monitoring of patients eligible for systemic therapy, using a 10-point Likert scale in a modified eDelphi voting process. The consensus was pre-defined as ≥70% of all respondents rating agreement as 7 (‘mildly agree’), 8 (‘moderately agree’), 9 (‘agree’) or 10 (‘strongly agree’) with a recommendation. A strong consensus was defined as ≥90% agreement. Expert perspectives and patient insights led to the development of 34 patient-focused clinical recommendations on disease severity assessments, treatment goals and targets for clinician- and patient-reported outcomes, long-term disease control and a novel minimal disease activity (MDA) concept. A consensus of ≥80% was reached for all recommendations in one round of voting, with 88% of the recommendations reaching a ‘strong’ consensus. The MDA concept combines T2T principles with shared patient/clinician treatment decision-making principles. Patients are asked to select 1–3 feature(s) of AD which are most important to them (from the itch, skin appearance/condition, sleep disturbance, mental health, skin pain and impact on daily life). The clinician is asked to choose an objective measure of disease (from the Eczema Area and Severity Index [EASI], SCORing AD and/or the Investigator’s Global Assessment and body surface area). Treatment targets are then chosen from a list of ‘moderate’ and ‘optimal’ targets based on discussions between the clinician and patient. Optimal treatment targets include ≥90% improvement in EASI and a numeric rating scale of ≤ 1 for peak pruritus, sleep, and pain. Achievement of ‘optimal’ targets is defined as MDA. This international group of AD experts developed a novel MDA concept and criteria, which builds upon existing T2T work by providing a patient-centric approach to the optimal treatment of AD. The criteria and patient-focused clinical recommendations will help to identify and monitor patients with AD who could benefit from systemic therapy.

Atopic dermatitis (AD) is a common, chronic inflammatory skin disease often associated with a significant long-term disease burden. AD can profoundly impact a patient’s physical and mental health. Current AD management recommendations do not capture patient perspectives on their treatment needs, expectations and drivers of decision-making. Qualitative patient research is needed to support the creation of patient-centric recommendations for AD assessment and management. To study a large, international, ethnically diverse population of patients with AD that will enable the creation of patient-centric recommendations for AD management. Adult patients (≥18 years old) receiving treatment for AD were recruited from patient market research databases, clinician referrals, and local advertising. All patients were screened via a questionnaire to ensure a balanced and diverse range of ages, gender, educational levels, geographic locations, and AD severities, and to confirm that they were currently receiving treatment for AD. Patients participated in a 45-minute, 1 : 1 telephone interview conducted in their native language by the research team. These interviews explored the impact of AD on patients’ lives, patients’ most troublesome symptoms, how patients make treatment decisions and patients’ treatment expectations. Patients were also questioned on their current knowledge of AD scoring systems and what they thought was most important to include in AD scoring systems. A large ethnically diverse global patient population (N = 88; 15 countries) was included in the study. AD was reported to have a substantial, broad impact on patients’ lives, with patients being affected by AD at all times of the day and night. Itch, skin redness, dry/flaky skin and sleep disturbance were the most frequently reported signs and symptoms, with over 75% of patients experiencing them every 1–3 days. The itch was cited by 37% of patients as being the primary reason for changing AD treatments. In addition, the research revealed that mental health issues such as anxiety and depression are common in patients suffering from AD, and these features have the greatest negative impact on patients’ daily lives. Patients reported that AD impairs their quality of life, with many perceiving that clinicians underestimate this burden; this was reported more often for non-specialists compared with dermatologists. Patients also felt they were often not given enough time to express themselves in medical appointments and reported an inability to optimally communicate with their clinicians. Patients had little awareness of AD severity scoring systems, with almost no survey respondents reporting their use during previous healthcare encounters. When questioned about their preferences for different AD scoring systems, patients favoured using a combination of patient-reported outcomes to reflect disease burden and clinician-reported outcomes to ensure consistency across different physicians and patient populations. These preferences indicate that an optimal scoring system would consider a diverse range of symptoms, and the variable nature of AD, and be accessible regardless of education level. No single AD scoring system was preferred by all patients. Patients indicated that they would like AD scoring systems to be incorporated into clinical practice, to help them communicate their AD burden to clinicians, and to provide a clear framework for monitoring treatment response. This global patient study generated insights into the burden of AD on patients’ lives, their expectations of treatment, and their views on AD scoring methods. Results provided an evidence base for the development of patient-centric recommendations for AD management.

Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, had a superior efficacy vs. dupilumab in head-to-head randomized trials in moderate-to-severe atopic dermatitis (AD). Data on patients who switched from dupilumab to abrocitinib have been limited. To evaluate abrocitinib response in patients with moderate-to-severe AD who were responders or nonresponders to dupilumab. Dupilumab-treated patients from the JADE DARE trial (NCT04345367), which was designed to compare the efficacy and safety of 26-week abrocitinib (200 mg daily) vs. dupilumab (300 mg bi-weekly) in patients receiving topical medicated therapy, had the option to switch to abrocitinib 200 mg by enrolling to an open-label JADE EXTEND trial (NCT03422822). In this analysis, we evaluated the response to abrocitinib 200 mg at week 12 of JADE EXTEND of responders and nonresponders to dupilumab at week 26 of JADE DARE. Response and nonresponse were defined as patients’ achievement and nonachievement, respectively, of ≥50%, ≥ 75% or ≥90% improvement from the JADE DARE baseline in Eczema Area and Severity Index (EASI-50, EASI-75 or EASI-90), ≥ 4-point improvement from JADE DARE baseline in Peak Pruritus Numerical Rating Scale (PP-NRS4), and PP-NRS score of 0 or 1 (PP-NRS 0/1) at week 26 of JADE DARE. In addition, changes in individual EASI and PP-NRS scores were evaluated in dupilumab-treated patients with significant skin lesions (EASI ≥16) or itch burden (PP-NRS ≥7) at week 26 of JADE DARE. Patients who withdrew from JADE EXTEND were considered nonresponders after withdrawal. Additionally, adverse events (AEs) of dupilumab-treated patients from JADE DARE occurring during JADE EXTEND were assessed. Out of 365 dupilumab-treated patients in JADE DARE, 312 received treatment in JADE EXTEND. After 12 weeks of switching to abrocitinib, EASI-50 response was maintained in 98% of patients (277/282) who had attained EASI-50 after 26 weeks of dupilumab. Those values were 95% (232/245) for EASI-75, 88% (143/162) for EASI-90, 91% (192/210) for PP-NRS4 and 79% (86/109) for PP-NRS 0/1. Conversely, among patients who did not attain EASI-50 after 26 weeks of dupilumab, switching to abrocitinib for 12 weeks resulted in 75% (12/16) of patients attaining this level of response. Those values were 77% (41/53) for EASI-75, 62% (85/136) for EASI-90, 51% (46/90) for PP-NRS4 and 45% (86/192) for PP-NRS 0/1. Among dupilumab-treated patients with EASI ≥16 at week 26 of JADE DARE, 91% (10/11) experienced improvements (i.e. EASI

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.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.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.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).Continued tralokinumab treatment plus TCS as needed provides progressive and sustained improvements in AD signs, symptoms, and health-related QoL over 32 weeks.NCT03363854; study start date: 22 February 2018; primary completion date: 8 March 2019; study completion date: 26 September 2019.Atopic dermatitis (AD) is a chronic inflammatory disease that causes excessively dry and itchy skin that can negatively impact sleep and overall quality of life for patients. Topical corticosteroids (TCS) are the most common medication used for AD, but they are not able to control the most severe cases. Tralokinumab is a treatment injected under the skin that targets an immune messenger protein called interleukin 13, which plays a key role in driving the signs and symptoms of AD. The ECZTRA 3 clinical trial, funded by LEO Pharma, compared the use of TCS as needed with either tralokinumab or placebo in over 350 adult patients with moderate-to-severe AD over a 32-week period. After 16 weeks, more patients taking tralokinumab plus TCS had clear or almost clear skin compared with patients taking placebo plus TCS. Patients taking tralokinumab also used less TCS than patients taking placebo. In new analyses presented here, we found that the proportion of patients with clear or almost clear skin continued to increase with on-going treatment from Week 16 to Week 32. Tralokinumab plus TCS treatment also led to clinically meaningful improvements in outcomes important to patients, including itch, sleep, and quality of life. Improvements occurred early, within the first few weeks of therapy, and lasted through Week 32. Our assessment of multiple outcomes over time clearly demonstrates the positive impact of tralokinumab on different aspects of AD.

The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited.In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16.A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Nausea occurred in 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group, and acne occurred in 6.6% and 2.9%, respectively.In this trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.).