Interpreting the Relationship Among Itch, Sleep, and Work Productivity in Patients with Moderate-to-Severe Atopic Dermatitis: A Post Hoc Analysis of JADE MONO-2.

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.

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.

Efficacy and Safety of Abrocitinib in Patients with Severe and/or Difficult-to-Treat Atopic Dermatitis: A Post Hoc Analysis of the Randomized Phase 3 JADE COMPARE Trial.

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.

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.

Efficacy and safety of abrocitinib monotherapy in adolescents and adults: a post hoc analysis of the phase 3 JAK1 atopic dermatitis efficacy and safety (JADE) REGIMEN clinical trial.

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

Early Itch Response with Abrocitinib Is Associated with Later Efficacy Outcomes in Patients with Moderate-to-Severe Atopic Dermatitis: Subgroup Analysis of the Randomized Phase III JADE COMPARE Trial.

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. 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).

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.

Real-World Effectiveness of Newly Initiated Systemic Therapy for Atopic Dermatitis in the United States: A Claims Database Analysis.

INTRODUCTION: Atopic dermatitis (AD) is associated with significant quality-of-life and economic burdens. Real-world evidence is needed to identify optimal treatment pathways for AD. Here we evaluate real-world effectiveness of systemic therapies for moderate-to-severe AD in the USA. METHODS: Data (September 2016 to December 2019) were from the IQVIA Health Plan Claims data set (IQVIA, Danbury, CT) from patients aged 12 years or older with AD (ICD-9/10-CM, 691.8/L20.x) initiating a systemic immunosuppressive (SIS) agent (methotrexate, cyclosporine, mycophenolate, or azathioprine) or dupilumab and continuously enrolled for at least 6 months before and after the index date. Indicators of non-response (i.e., adding on/switching systemic therapy, AD-related inpatient/emergency room visits, or incident staphylococcal/streptococcal skin infection) and predictors of non-response were evaluated. Descriptive statistics and Kaplan-Meier rates and times were obtained; Cox regression models were used. RESULTS: In 3249 patients, 45.4% exhibited at least one indicator of non-response, with median time to non-response being longer for dupilumab than for any SIS therapy (27.0 vs 4.0-7.7 months, respectively). Key non-response predictors were age, geographic region, and baseline number of annual AD-related medical visits. CONCLUSION: Non-response was common in patients with AD who required systemic treatment, and non-response indicators occurred significantly more frequently with SIS treatment than with dupilumab treatment.

Predictors of nonresponse to dupilumab in patients with atopic dermatitis: A machine learning analysis.

BACKGROUND: Many patients with atopic dermatitis (AD) have a suboptimal response to systemic therapy. OBJECTIVE: This study assessed predictors of nonresponse to dupilumab in patients with AD. METHODS: Data (April 2017 through June 2019) for patients aged 12 years and above with AD (International Classification of Diseases-9/10-Clinical Modification: 691.8/L20.x) who initiated dupilumab on or after April 1, 2017 (index date) were collected from an electronic health record and insurance claims database. Nonresponse indicators (dupilumab discontinuation, addition of another systemic therapy or phototherapy, addition of a high-potency topical corticosteroid, AD-related hospital visit, AD-related emergency department visit, incident skin infection) were predicted from available demographic and clinical variables using machine learning. RESULTS: Among 419 patients (mean age: 45 years), 145 (35%) experienced at least 1 indicator of nonresponse in the 6-month postindex period. In patients with at least 1 indicator, the most common was dupilumab discontinuation (47% [68/145]). Of note, this analysis could not capture nonmedical reasons for dupilumab discontinuation (eg, cost, access). The most common predictors of nonresponse were a claim for ibuprofen (in 69% of patients with a nonresponse indicator) and a Quan-Charlson Comorbidity Index value of 3 to 4 (59%). CONCLUSION: Systemic dupilumab therapy for AD can be associated with a relatively high prevalence of nonresponse indicators. Factors associated with these indicators-that is, predictors of nonresponse-may be used to optimize disease management.

Atopic dermatitis and risk of autoimmune conditions: Population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) is associated with immune dysregulation, but epidemiologic data on the pattern of autoimmune comorbidity in people with AD are limited. OBJECTIVE: We sought to determine the risk of autoimmune conditions in people newly diagnosed with AD. METHODS: Retrospective cohort analysis (January 2009 to December 2018), using the UK-based Oxford-Royal College of General Practitioners Research and Surveillance Centre primary care database. We compared baseline prevalence and incidence after diagnosis of autoimmune conditions in 173,709 children and adults with new-onset AD and 694,836 age-, sex-, and general practitioner practice-matched controls. Outcomes were a composite of any autoimmune condition (Crohn disease, ulcerative colitis, celiac disease, pernicious anemia, type 1 diabetes, autoimmune hypothyroidism, Graves disease, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, Sjögren syndrome, vitiligo, alopecia areata, and multiple sclerosis) and each individual autoimmune condition. RESULTS: Preexisting autoimmune conditions were more common in people diagnosed with AD compared to controls (composite 5.8% vs 4.3%). Excluding people with preexisting autoimmune disease, there was an association between AD and incidence of new-onset autoimmune disease (composite adjusted hazard ratio [aHR] 1.28; 95% confidence interval [CI] 1.23-1.34). Risk was highest for more severe AD (aHR 1.99; 95% CI 1.77-2.23) than moderate AD (aHR 1.33; 95% CI 1.19-1.49) or mild AD (aHR 1.22; 95% CI 1.16-1.28). People with AD were at significantly increased risk of developing psoriatic arthritis, Sjögren syndrome, Crohn disease, vitiligo, alopecia areata, pernicious anemia, ulcerative colitis, rheumatoid arthritis, and hypothyroidism (aHR range 1.17-2.06), but not other autoimmune conditions. CONCLUSION: People with AD have an increased risk of multiple autoimmune conditions, especially those with more severe AD.

Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial.

BACKGROUND: The heterogeneous course of moderate-to-severe atopic dermatitis necessitates treatment flexibility. OBJECTIVE: We evaluated the maintenance of abrocitinib-induced response with continuous abrocitinib treatment, dose reduction or withdrawal, and response to treatment reintroduction following flare (JAK1 Atopic Dermatitis Efficacy and Safety [JADE] REGIMEN: National Clinical Trial 03627767). METHODS: Patients with moderate-to-severe atopic dermatitis responding to open-label abrocitinib 200 mg monotherapy for 12 weeks were randomly assigned in a 1:1:1 ratio to blinded abrocitinib (200 or 100 mg) or placebo for 40 weeks. Patients experiencing flare received rescue treatment (abrocitinib 200 mg plus topical therapy). RESULTS: Of 1233 patients, 798 responders to induction (64.7%) were randomly assigned. The flare probability during maintenance was 18.9%, 42.6%, and 80.9% with abrocitinib 200 mg, abrocitinib 100 mg, and placebo, respectively. Among patients with flare in the abrocitinib 200 mg, abrocitinib 100 mg, and placebo groups, 36.6%, 58.8%, and 81.6% regained investigator global assessment 0/1 response, respectively, and 55.0%, 74.5%, and 91.8% regained eczema area and severity index response, respectively, with rescue treatment. During maintenance, 63.2% and 54.0% of patients receiving abrocitinib 200 and 100 mg, respectively, experienced adverse events. LIMITATIONS: The definition of protocol-defined flare was not established, limiting the generalizability of findings. CONCLUSION: Induction treatment with abrocitinib was effective; most responders continuing abrocitinib did not flare. Rescue treatment with abrocitinib plus topical therapy effectively recaptured response.

Symptom burden of patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with intense and persistent pruritus. OBJECTIVES: To examine associations between AD symptoms and health-related quality of life (HRQoL) in adults (aged ≥18 years) with moderate-to-severe AD. MATERIALS & METHODS: Patient chart and survey data from physicians within Europe were derived from the Adelphi AD Disease Specific Programme (Q3 2019-Q2 2020). HRQoL measures included Euro-Qol 5-dimension, 3-level, questionnaire; Dermatology Life Quality Index; and Work Productivity and Activity Impairment-Atopic Dermatitis questionnaire. Data were evaluated using descriptive statistics and generalized linear models. RESULTS: Of 631 patients, 90.1%, 49.3%, 18.5% and 17.7% reported pruritus, sleep disruption, anxiety and depression, respectively. Adjusted analyses indicated an increased frequency of symptoms associated with worse HRQoL and greater work/activity impairments, particularly for patients with pruritus and sleep disruption. CONCLUSION: Reductions in symptom frequency may have important implications for improving the overall health of patients with moderate-to-severe AD.

Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial.

Importance: Dupilumab subcutaneous injection is approved for treating moderate-to-severe atopic dermatitis (AD) in adolescents, but there has been too little research on an efficacious systemic oral treatment with a favorable benefit-risk profile for adolescents with moderate-to-severe AD. Objective: To investigate the efficacy and safety of oral abrocitinib plus topical therapy in adolescents with moderate-to-severe AD. Design, Setting, and Participants: The phase 3, randomized, double-blind, placebo-controlled study JADE TEEN was conducted in countries of the Asia-Pacific region, Europe, and North America in patients aged 12 to 17 years with moderate-to-severe AD and an inadequate response to 4 consecutive weeks or longer of topical medication or a need for systemic therapy for AD. The study was conducted between February 18, 2019, and April 8, 2020. The data were analyzed after study completion. Interventions: Patients were randomly assigned 1:1:1 to receive once-daily oral abrocitinib, 200 mg or 100 mg, or placebo for 12 weeks in combination with topical therapy. Main Outcomes and Measures: Coprimary end points were achievement of an Investigator's Global Assessment (IGA) response of clear (0) or almost clear (1) with improvement of 2 or more grades from baseline (IGA 0/1) and 75% or greater improvement from baseline in Eczema Area and Severity Index (EASI-75) response at week 12. Key secondary end points included 4-point or greater improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 12. Adverse events (AEs) were monitored. Results: This study included 285 adolescents with moderate-to-severe AD (145 boys [50.9%] and 140 girls [49.1%]), of whom 160 (56.1%) were White and 94 (33.0%) were Asian; the median age was 15 years (interquartile range 13-17 years). Substantially more patients treated with abrocitinib (200 mg or 100 mg) vs placebo achieved an IGA response of 0/1 (46.2%; 41.6% vs 24.5%; P < .05 for both), EASI-75 (72.0%; 68.5% vs 41.5%; P < .05 for both), and PP-NRS4 (55.4%; 52.6% vs 29.8%; P < .01 for 200 mg vs placebo) at week 12. Adverse events were reported for 59 (62.8%), 54 (56.8%), and 50 (52.1%) patients in the 200 mg, 100 mg, and placebo groups, respectively; nausea was more common with abrocitinib, 200 mg (17 [18.1%]) and 100 mg (7 [7.4%]). Herpes-related AEs were infrequent; 1 (1.1%), 0, and 2 (2.1%) patients had serious AEs. Conclusions and Relevance: This randomized clinical trial found that oral abrocitinib combined with topical therapy was significantly more effective than placebo with topical therapy in adolescents with moderate-to-severe AD, with an acceptable safety profile. Trial Registration: ClinicalTrials.gov identifier: NCT03796676.

A 'Real Life' Service Evaluation Model for Multidisciplinary Thyroid Eye Services.

Background/Aims: There is no universal consensus on the practical implementation and evaluation of the Amsterdam Declaration on Graves Orbitopathy in a Multidisciplinary Thyroid Eye Disease (MDTED) pathway. Recent recommendations from the UK TEAMeD-5 and BOPSS initiative highlight the importance of prevention, screening, and prompt referral of patients with moderate to severe and sight-threatening thyroid eye disease to multidisciplinary (MDTED) clinics and recommends annual auditing. We propose a practical service evaluation model with Key Performance Indicators (KPI) that are achievable and could be implemented across most TED pathways. Material and Methods: We conducted a service evaluation from an integrated TED pathway in London with three MDTED clinics. Data was collected retrospectively from consecutive TED patients included: 1) Patient demographics, 2) Referral to first appointment time, 3) Documented smoking cessation and selenium supplementation advice, 4) Presenting disease activity and severity, 5) Investigations and treatments, including radio-iodine, 6) Time from decision to treatment initiation, 7) Initial and subsequent thyroid status. Results: The median age was 49.0 yrs, 77.5% (183/236) were female and 49.5% (101/204) Afro-Caribbean or Asian. At their first clinic attendance, 47.6% (110/231) were biochemically euthyroid and 76.7% (79/103) at discharge. All 23.1% (52/225) current smokers received smoking cessation advice and 64.8% (153/236) received selenium supplementation advice. Intravenous methylprednisolone was given to 33.9% (80/236) patients and 12.7% (30/236) received second-line immunosuppression. All 7.2% (17/236) patients with sight-threatening disease received treatment within two weeks of diagnosis. Conclusions: This study forms a waymark for other units using TEAMeD-5 and BOPSS audit criteria. Dedicated electronic patient records with ongoing data capture, including quality of life assessments, and diagnostic coding would significantly aid future auditing, improve patient care, and facilitate a national audit of TED management. A future survey when the TED standards have become embedded would be instructive to see whether this has improved TED care.

Impact of Oral Abrocitinib Monotherapy on Patient-Reported Symptoms and Quality of Life in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis: A Pooled Analysis of Patient-Reported Outcomes.

BACKGROUND: Atopic dermatitis imparts a substantial patient burden, including itch, sleep disturbance, and decreased health-related quality of life. OBJECTIVE: This analysis evaluated changes in patient-reported outcomes of disease-specific signs/symptoms and health-related quality of life in adult and adolescent patients with moderate-to-severe atopic dermatitis treated with once-daily oral abrocitinib 200-mg or 100-mg monotherapy. METHODS: Pooled data from one phase IIb (NCT02780167) and two phase III (NCT03349060, JADE MONO-1; NCT03575871, JADE MONO-2) monotherapy trials in adult and adolescent patients with moderate-to-severe atopic dermatitis were analyzed. Patient-reported outcome assessments included: global severity, itch, and multi-item measures that assess other signs and symptoms of atopic dermatitis. Additional patient-reported outcome assessments measured depression, anxiety, fatigue, disease-specific and general health-related quality of life, and work and general productivity among employed patients. RESULTS: Overall, 942 patients were included in this analysis. Improvements were observed from the first post-baseline assessment to week 12 across all patient-reported outcomes, including Patient Global Assessment (PtGA) score of 0/1 (35.5%, 19.8%, and 5.9% for 200 mg, 100 mg, and placebo, respectively), ≥ 4-point improvement in Night Time Itch Scale (NTIS; 57.0%, 42.7%, and 12.7%), change from baseline in Patient-Oriented Eczema Measure (POEM) score (- 11.4, - 8.2, and - 3.4), 1-point improvement in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD; 75.2%, 65.1%, and 33.5%), Hospital Anxiety and Depression Scales (HADS) anxiety (- 2.0, - 1.7, and - 1.0) and depression (- 1.7, - 1.3, and - 0.1). CONCLUSIONS: Abrocitinib monotherapy improved disease-specific signs/symptoms and health-related quality of life across multiple domains as reported by adult and adolescent patients with moderate-to-severe atopic dermatitis, complementing clinician-reported efficacy and safety outcomes. CLINICAL TRIAL REGISTRATION: NCT02780167 (registered 23 May, 2016), NCT03349060 (registered 21 November, 2017), NCT03575871 (registered 3 July, 2018).

Association of Other Autoimmune Diseases With Thyroid Eye Disease.

Background: Thyroid eye disease (TED) is a potentially disfiguring and sight-threatening autoimmune (AI) orbitopathy, affecting up to 400,000 people in the UK. There are no accurate early predictors of TED severity. Although polyautoimmunity has been shown to affect AI disease severity, its influence on TED severity has never been investigated. The prevalence of polyautoimmunity among TED patients is also unclear, with discordant results reported in the literature. This study evaluates the prevalence of non-thyroid/"other" AI (OAI) conditions in an ethnically diverse TED cohort and assesses how polyautoimmunity affects TED severity and activity. Methods: A retrospective study of patients presenting to multidisciplinary TED clinics across three North-West London hospitals between 2011 and 2019. Data collected included: 1) demographics; 2) OAI conditions and management; 3) endocrine management of thyroid dysfunction; 4) details of TED and clinical activity score at presentation. Results: Two hundred and sixty-seven patients with a median age of 46 (35-54) years were included, 79.4% were female and 55% were Black, Asian and minority ethnic (BAME). Thirty-seven patients (13.9%) had OAI conditions, with rheumatoid arthritis (3.7%), vitiligo (3.0%) and psoriasis (3.0%) among the most prevalent. Of patients with OAI conditions, 43.2% (16/37) required immunosuppression prior to TED onset. Non-immunosuppressed patients with OAI conditions had a significantly higher clinical activity score at presentation than TED-only and previously immunosuppressed patients (p=0.02). No significant differences were observed in thyroid receptor antibody titers between these groups. Conclusions: This study finds a 13.9% prevalence of OAI conditions among TED patients. Patients with OAI conditions overall have a tendency for more severe and significantly more clinically active TED than those without OAI conditions. Larger, prospective studies are warranted to further evaluate polyautoimmunity as an early predictor of TED severity.

The epidemiology of eczema in children and adults in England: A population-based study using primary care data.

BACKGROUND: Whilst eczema is a common inflammatory skin condition, we lack contemporary estimates of disease incidence and prevalence across the lifespan. OBJECTIVE: To estimate the incidence and prevalence of eczema in children and adults in England and variation by sociodemographic factors (sex, socio-economic status, ethnicity, and geography). METHODS: We used the Royal College of General Practitioners Research and Surveillance Centre primary care research database of 3.85 million children and adults registered with participating general practitioner practices between 2009 and 2018 inclusive. Eczema incidence was defined as the first-ever diagnosis of eczema recorded in the primary care record, and eczema prevalence was defined as fulfilment of criteria for active eczema (two eczema records appearing in the primary care record within any one-year period). RESULTS: Eczema incidence was highest in infants younger than 1 year (15.0 per 100 person-years), lowest in adults aged 40-49 (0.35 p/100 person-years), and increased from middle age to a second smaller peak in people 80 years or older (0.79 p/100 person-years). Eczema prevalence was highest in children aged 2 (16.5%) and lowest in adults aged 30-39 (2.8%). Eczema incidence was higher in male infants (<2) and male adults older than 70; for all other ages, incidence was higher in females. Eczema was more common in Asian and black ethnic groups than in people of white ethnicity. Higher socio-economic status was associated with a greater incidence of eczema in infants younger than 2, but the reverse was seen for all other age groups. Both incidence and prevalence of eczema were greater in urban settings and in North-West England. CONCLUSIONS AND CLINICAL RELEVANCE: Eczema has a bimodal distribution across the lifespan. We observed differences in incidence and prevalence of eczema by ethnicity, geography, sex, and socio-economic status, which varied in magnitude throughout life.

Epidemiology and management of atopic dermatitis in England: an observational cohort study protocol.

INTRODUCTION: Atopic dermatitis (AD) is one of the most common inflammatory skin conditions in both children and adults. Despite this, contemporary descriptions of the incidence, prevalence and current management of the condition in the UK are lacking. METHODS AND ANALYSIS: We will perform a series of retrospective studies using a large population-based cohort derived from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database to explore two key research themes: AD epidemiology and AD management.In the epidemiology theme, we will describe the incidence and prevalence of AD in children and adults in England from 2009 to 2018 inclusive. We will stratify findings by age, national Index of Multiple Deprivation (IMD), ethnicity, urban-rural environment and geographic location; and explore independent associations of these features with AD in multivariable models.In the management theme, we will explore healthcare utilisation and treatment in people with AD. Regarding healthcare utilisation, we will evaluate rates of AD-associated primary care visits and specialist dermatology referrals in people with AD. Rates will be stratified by age, gender, socioeconomic IMD quintile and ethnicity. We will describe contemporary treatment by estimating prescribing rates across medication classes used in AD (emollients, topical corticosteroids by potency, topical calcineurin inhibitors, topical antimicrobials, antihistamines, oral corticosteroids and systemic immunomodulatory therapies) overall, and by age and sociodemographic groupings. We will also examine trends in prescribing over the study period. In people first diagnosed with AD during the study period, we will describe differences in treatment escalation by sociodemographic factors using time-to-event analysis. ETHICS AND DISSEMINATION: The Health Research Authority decision tool classed this a study of 'usual practice', ethics approval was not required. Study approval was granted by the RCGP RSC Study Approval Committee. Results will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03823794.

Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis. METHODS: In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060. FINDINGS: Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported. INTERPRETATION: Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis. FUNDING: Pfizer.

Efficacy and Safety of Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial.

Importance: Abrocitinib, an oral, once-daily Janus kinase 1 selective inhibitor, was effective and well tolerated in a phase 3 monotherapy trial of patients with moderate-to-severe atopic dermatitis (AD). Objective: To investigate the efficacy and safety of abrocitinib in adolescents and adults with moderate-to-severe AD in an identically designed trial. Design, Setting, and Participants: This phase 3, double-blinded, placebo-controlled, parallel-group randomized clinical trial included patients 12 years or older with a clinical diagnosis of moderate-to-severe AD for at least 1 year and inadequate response to topical medications given for at least 4 weeks within 6 months. Patients were enrolled from 115 centers in Australia, Bulgaria, Canada, China, Czechia, Germany, Hungary, Japan, South Korea, Latvia, Poland, United Kingdom, and the United States from June 29, 2018, to August 13, 2019. Data were analyzed from September 13 to October 25, 2019. Interventions: Patients were randomly assigned (2:2:1) to receive once-daily oral abrocitinib in 200- or 100-mg doses or placebo for 12 weeks. Main Outcomes and Measures: The coprimary end points were the proportion of patients achieving Investigator Global Assessment (IGA) response (ie, clear [0] or almost clear [1], with improvement of ≥2 grades) and the proportion of patients achieving at least 75% improvement in Eczema Area and Severity Index score (EASI-75) at week 12. Key secondary end points included the proportion of patients achieving a Peak Pruritus Numerical Rating Scale (PP-NRS) response (ie, improvement of ≥4 points) at week 12. Other secondary end points included the proportion of patients achieving at least 90% improvement in EASI score (EASI-90). Safety was assessed via adverse events and laboratory monitoring. Results: A total of 391 patients (229 male [58.6%]; mean [SD] age, 35.1 [15.1] years) were included in the analysis; of these, 155 received abrocitinib, 200 mg/d; 158, abrocitinib, 100 mg/d; and 78, placebo. Among patients with available data at week 12, greater proportions of patients in the 200- and 100-mg abrocitinib groups vs the placebo group achieved IGA (59 of 155 [38.1%] and 44 of 155 [28.4%] vs 7 of 77 [9.1%]; P < .001) and EASI-75 (94 of 154 [61.0%] and 69 of 155 [44.5%] vs 8 of 77 [10.4%]; P < .001), greater estimated proportions achieved PP-NRS (55.3% [95% CI, 47.2%-63.5%] and 45.2% [95% CI, 37.1%-53.3%] vs 11.5% [95% CI, 4.1%-19.0%]; P < .001), and/or greater proportions achieved EASI-90 (58 of 154 [37.7%] and 37 of 155 [23.9%] vs 3 of 77 [3.9%]) responses. Adverse events were reported for 102 patients (65.8%) in the 200-mg group, 99 (62.7%) in the 100-mg group, and 42 (53.8%) in the placebo group; serious adverse events were reported for 2 patients (1.3%) in the 200-mg group, 5 (3.2%) in the 100-mg group, and 1 (1.3%) in the placebo group. Decreases in platelet count (2 [1.3%]) and laboratory values indicating thrombocytopenia (5 [3.2%]) were reported in the 200-mg group. Conclusions and Relevance: Monotherapy with once-daily oral abrocitinib was effective and well tolerated in adolescents and adults with moderate-to-severe AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03575871.

Cognitive impairment and health-related quality of life following traumatic brain injury.

BACKGROUND: Cognitive impairment is a common and disabling consequence of traumatic brain injury (TBI) but its impact on health-related quality of life is not well understood. OBJECTIVE: To investigate the relationship between cognitive impairment and health-related quality of life (HRQoL) after TBI. METHODS: Retrospective, cross-sectional study of a specialist TBI outpatient clinic patient sample. OUTCOME MEASURES: Addenbrooke's Cognitive Examination Tool - Revised (ACE-R), and SF-36 quality of life, Beck Depression Inventory II (BDI-II), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaires. RESULTS: 240 adults were assessed: n = 172 (71.7%) moderate-severe, 41 (23.8%) mild, 27 (11.3%) symptomatic TBI, 174 (72.5%) male, median age (range): 44 (22-91) years. TBI patients reported poorer scores on all domains of SF-36 compared to age-matched UK normative data. Cognitively impaired patients reported poorer HRQoL on the physical, social role and emotional role functioning, and mental health domains. Cognitive impairment predicted poorer HRQoL on the social and emotional role functioning domains, independently of depressive symptoms, sleep disturbance, daytime sleepiness and TBI severity. Mediation analysis revealed that the effect of depressive symptoms on the emotional role functioning domain of HRQoL was partially mediated by cognitive dysfunction. CONCLUSION: Cognitive impairment is associated with worse health-related quality of life after TBI and partially mediates the effect of depressive symptoms on emotional role functioning.