Interim analyses of a first-in-human phase 1/2 mRNA trial for propionic acidaemia.

Propionic acidaemia is a rare disorder caused by defects in the propionyl-coenzyme A carboxylase α or ß (PCCA or PCCB) subunits that leads to an accumulation of toxic metabolites and to recurrent, life-threatening metabolic decompensation events. Here we report interim analyses of a first-in-human, phase 1/2, open-label, dose-optimization study and an extension study evaluating the safety and efficacy of mRNA-3927, a dual mRNA therapy encoding PCCA and PCCB. As of 31 May 2023, 16 participants were enrolled across 5 dose cohorts. Twelve of the 16 participants completed the dose-optimization study and enrolled in the extension study. A total of 346 intravenous doses of mRNA-3927 were administered over a total of 15.69 person-years of treatment. No dose-limiting toxicities occurred. Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period.

A systematic review of real-world evidence (RWE) supportive of new drug and biologic license application approvals in rare diseases.

BACKGROUND: Real-world evidence (RWE) generated using real-world data (RWD) presents the potential to contextualize and/or supplement traditional clinical trials for regulatory approval of rare diseases (RDs). This systematic review evaluated the use of RWD for non-oncologic RD therapies with orphan drug designation (ODD) to support efficacy outcomes in regulatory application packages to the US Food and Drug Administration (FDA). New drug applications (NDAs) and biologic license applications (BLAs) submitted between January 2017 and October 2022 were obtained from publicly available FDA drug approval websites. NDAs and BLAs of non-oncologic RD therapies were screened, and manually reviewed using RWE-related keywords. Quantitative summary of number/proportion of study types was provided, whereas qualitative synthesis focused on key categories of output assessing the use of RWD in overall drug approval process, including agency's feedback on its strengths and key challenges. RESULTS: A total of 868 NDAs and BLAs were identified, of which 243 were screened for non-oncologic RDs with ODD, and 151 were subsequently reviewed for the RWD used to support efficacy outcomes. Twenty (12 NDAs, 8 BLAs) applications met the review inclusion criteria. Most (19; 95%) applications used only retrospective RWD, while one (5%) collected RWD both retrospectively and prospectively. RWD studies included natural history including registry-based/retrospective historical controls (14; 70%), retrospective medical chart-reviews (4; 20%), and external RWD controls from other studies (2; 10%). The FDA generally accepted RWD studies demonstrating a large effect size despite the noted concerns and criticisms. However, the agency expressed concerns about overall quality and comparability of RWD with trial data for some applications, including RWD study designs with respect to differences in patients' baseline characteristics, missing information, and potential bias and measurement errors. CONCLUSIONS: This systematic review highlights potential benefits of appropriately conducted RWE studies in RD, which can strengthen the clinical evidence for efficacy comparison and contextualization to support product approval efforts, particularly when a large magnitude of effect is observed for the new intervention. Nonetheless, quality and completeness of RWD and its comparability with trial data remain areas of concern that can serve as valuable learnings for advancing future science and regulatory approvals.

Retrospective study of propionic acidemia using natural language processing in Mayo Clinic electronic health record data.

BACKGROUND: Propionic acidemia (PA) is a rare autosomal recessive organic acidemia that classically presents within the first days of life with a metabolic crisis or via newborn screening and is confirmed with laboratory tests. Limited data exist on the natural history of patients with PA describing presentation, treatments, and clinical outcomes. OBJECTIVE: To retrospectively describe the natural history of patients with PA in a clinical setting from a real-world database using both structured and unstructured electronic health record (EHR) data using novel data extraction techniques in a unique care setting. DESIGN/METHODS: This retrospective study used EHR data to identify patients with PA seen at the Mayo Clinic. Unstructured clinical text (medical notes, pathology reports) were analyzed using augmented curation natural language processing models to enhance analysis of data extracted by structured data fields (International Classification of Diseases 9th or 10th revision [ICD-9/-10] codes, Current Procedural Terminology [CPT] codes, and medication orders). De-identified health records were also manually reviewed by clinical scientists to ensure data accuracy and completeness. The index date was defined as the patient's date of PA diagnosis at the Mayo Clinic. Results were reported as aggregate descriptive statistics relative to patients' index dates. Complications, therapeutic interventions, laboratory tests, procedures, and hospitalization encounters related to PA were described at and within 6 months of the patient's index date, and from medical history available before the index date. RESULTS: In total, 13 patients with PA were identified, with visits occurring from 1998 to 2022. Age at diagnosis ranged from birth to 3 years; age at initial evaluation at the Mayo Clinic ranged from 3 days to 28 years. The mean number of Mayo Clinic outpatient visits was 31 (median duration of care, 2 years). PA-related complications were documented in 85% of patients and included nutritional difficulties (46%), metabolic decompensation events (MDEs; 38%), neurologic abnormalities (38%), and cardiomyopathy (7%). One pair of affected siblings had mild symptoms and no complications or MDEs. All 5 patients with a history of MDEs presented with developmental delays. Among patients with MDEs, the mean frequency of outpatient clinical care visits was 10 per year, and 3 patients required inpatient hospitalization (mean duration, 16 days). The incidence of severe complications was higher among patients with MDEs than those without MDEs. Of the patients with MDEs, 2 experienced crises while receiving treatment at the Mayo Clinic, with 9 total MDEs occurring between the 2 patients. Symptoms at presentation included hyperammonemia (78%), fever and/or decreased nutritional intake (67%), hyperglycemia/hypoglycemia (56%), intercurrent upper respiratory infection and/or lethargy (44%), constipation (33%), altered mental status (33%), and cough (33%). CONCLUSIONS: This study highlights the range and frequency of clinical outcomes experienced by patients with PA and demonstrates the clinical burden of MDEs.

Systematic literature review of the epidemiology of glycogen storage disease type 1a.

Glycogen storage disease (GSD) type 1a is an inherited autosomal recessive metabolic disease caused by a deficiency in glucose-6-phosphatase activity. The objectives of this research were to systematically review the published literature on the epidemiology of GSD 1a and to assess the performance of reported epidemiology measures in a simulation model. In this systematic literature review 2,539 record titles and abstracts were screened. Of these, only 11 studies contained relevant data on GSD 1a disease epidemiology. Reported disease frequency ranged from 0.085/100,000 to 10.3/100,000 newborns when considering all the GSD literature. When this was narrowed to GSD 1 and GSD 1a, the range was tightened to 0.25-3.02/100,000 and 0.085-4.9/100,000 newborns, respectively. Most of the identified studies counted the number of diagnoses in a defined period and related to the number of births in the same (Dx method) or different time period (DoB method). The simulation model results indicate that in most of the situations, the Dx method provides a closer estimate to the true disease incidence than the DoB method. Despite the scarcity of epidemiology data, the results of this systematic review strongly support that GSD 1a and its parent disease groups (GSD and GSD 1) are rare diseases.

Efficacy and Safety of the TYK2/JAK1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial.

OBJECTIVE: Brepocitinib is a TYK2/JAK1 inhibitor in development for the treatment of several immunologic diseases. The efficacy and safety of oral brepocitinib were assessed in participants with moderately-to-severely active psoriatic arthritis (PsA) for up to 52 weeks. METHODS: In this placebo-controlled, dose-ranging, phase IIb study, participants were randomized to receive 10 mg, 30 mg, or 60 mg of brepocitinib once daily or placebo, advancing to 30 mg or 60 mg of brepocitinib once daily at week 16. The primary endpoint was the response rate according to the American College of Rheumatology criteria for 20% improvement (ACR20) in disease activity at week 16. Secondary endpoints included response rates according to the ACR50/ACR70 response criteria, 75% and 90% improvement in the Psoriasis Area and Severity Index (PASI75/PASI90) score, and minimal disease activity (MDA) at weeks 16 and 52. Adverse events were monitored throughout the study. RESULTS: Overall, 218 participants were randomized and treated. At week 16, the brepocitinib 30 mg and 60 mg once daily groups had significantly greater ACR20 response rates (66.7% [P = 0.0197] and 74.6% [P = 0.0006], respectively), versus the placebo group (43.3%), and significantly higher ACR50/ACR70, PASI75/PASI90, and MDA response rates. Response rates were maintained or improved through week 52. Adverse events were mostly mild/moderate; serious adverse events (15) in 12 participants (5.5%) included infections in 6 participants (2.8%) in the brepocitinib 30 mg and 60 mg once daily groups. No major adverse cardiovascular events or deaths occurred. CONCLUSION: Treatment with brepocitinib at dosages of 30 mg and 60 mg once daily was superior to placebo at reducing signs and symptoms of PsA. Brepocitinib was generally well tolerated throughout the 52-week study, with a safety profile consistent with those found in other brepocitinib clinical trials.

Patient characteristics associated with all-cause healthcare costs of alopecia areata in the United States.

Evidence on the factors of medical costs involved in the care of people with alopecia areata (AA) is limited, but mounting evidence points to significant variation in financial impact for patients with AA in the absence of effective treatments. This study explored drivers of medical costs among privately insured adults and adolescents with AA in the United States. The study found that patients of middle age (45­64 years), located in the Northeast region, with comprehensive health insurance, with greater extent of hair loss, or with other health disorders face greater all-cause medical costs. Adult females of young (18­44 years) and older (65+ years) age also faced greater costs on average. This research confirms high variability in the burden of AA, pointing to population subgroups that may be more affected by the disease and its commonly associated disorders.

Prevalence of Vitiligo among Children and Adolescents in the United States.

BACKGROUND: Vitiligo is an autoimmune disorder that causes patchy loss of skin pigmentation. Up to 2.16% of pediatric patients may have vitiligo. This study estimated vitiligo point prevalence in children and adolescents (ages: 4-11 and 12-17 years) in the United States (US). METHODS: An online, population-based survey of a nationally representative sample of individuals based on 2017 US Census Bureau estimates for age, race, Hispanic origin, income, and geographic region was conducted from December 2019 to March 2020. Parent/legal guardian proxies responded on behalf of their children or adolescents to vitiligo screening questions. Proxy-reported vitiligo status was adjudicated by expert dermatologists who reviewed photographs of vitiligo lesions uploaded by proxies using a teledermatology application. Estimated point prevalence (including diagnosed and undiagnosed vitiligo and its subtypes) was calculated for proxy-reported and clinician-adjudicated vitiligo. RESULTS: There were 9,118 eligible proxy responses (5,209 children, mean age 7.7 years; 3,909 adolescents, mean age 14.4 years). The proxy-reported vitiligo prevalence (95% confidence interval) for children and adolescents was 1.52% (1.11-1.93) and 2.16% (1.66-2.65), respectively. The clinician-adjudicated prevalence (sensitivity analysis bounds) was 0.84% (0.83-1.23) and 1.19% (1.18-1.74), respectively. Approximately 69% of children and 65% of adolescents had nonsegmental vitiligo (clinician adjudicated) and up to 50% may be undiagnosed. CONCLUSION: Based on the clinician-adjudicated prevalence estimates, there were more than 591,000 cases of vitiligo in children and adolescents in the US in 2020. More than two-thirds had nonsegmental vitiligo and nearly half may be undiagnosed. Future studies should confirm these findings.

Healthcare Utilization and Costs Among US Adolescents With Alopecia Areata.

Background: Alopecia areata (AA) is an autoimmune disease of hair loss affecting people of all ages. Alopecia totalis (AT) and universalis (AU) involve scalp and total body hair loss, respectively. AA significantly affects quality of life, but evidence on the economic burden in adolescents is limited. Objectives: To assess healthcare resource utilization (HCRU) and all-cause direct healthcare costs, including out-of-pocket (OOP) costs, of US adolescents with AA. Methods: IBM MarketScan® Commercial and Medicare databases were used to identify patients aged 12-17 years with ≥2 claims with AA/AT/AU diagnosis (prevalent cases), from October 1, 2015, to March 31, 2018, enrolled for ≥12 months before and after the first AA diagnosis (index). Patients were matched 1:3 to non-AA controls on index year, demographics, plan type, and Charlson Comorbidity Index. Per patient per year HCRU and costs were compared post-index. Results: Patients comprised 130 AT/AU adolescents and 1105 non-AT/AU adolescents (53.8% female; mean age, 14.6 years). Post-index, AT/AU vs controls had more outpatient (14.5 vs 7.1) and dermatologist (3.6 vs 0.3) visits, higher mean plan costs ($9397 vs $2267), including medical ($7480 vs $1780) and pharmacy ($1918 vs $487) costs, and higher OOP costs ($2081 vs $751) (all P<.001). The non-AT/AU cohort vs controls had more outpatient (11.6 vs 8.0) and dermatologist (3.4 vs 0.4) visits, higher mean plan costs ($7587 vs $4496), and higher OOP costs ($1579 vs $805) (all P<.001). Discussion: This large-sample, real-world analysis found that adolescents with prevalent AA had significantly higher HCRU and all-cause costs than matched controls. The greater burden was driven by more frequent outpatient visits, and higher payer medical and pharmacy costs in comparison with controls. Oral corticosteroid use was higher among patients with AT/AU; topical and injectable corticosteroid use was higher for non-AT/AU. Although the data preclude the identification of AA-attributable costs, the matched-control design allows an estimation of incremental all-cause costs associated with AA. Conclusions: Adolescents with AA incurred substantial incremental healthcare costs, with greater costs incurred among those with AT/AU. Study findings suggest that AA incurs costs as a medical condition with a high burden on adolescent patients and health plans.

Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: a phase IIb, randomized, double-blind, vehicle-controlled, dose-ranging and parallel-group study.

BACKGROUND: Atopic dermatitis (AD) is a prevalent inflammatory, pruritic skin disease. The Janus kinase (JAK) pathway is a treatment target. OBJECTIVES: To assess the efficacy, safety and pharmacokinetics of topical cream brepocitinib, a small-molecule tyrosine kinase 2 (TYK2)/JAK1 inhibitor, in participants with mild-to-moderate AD. METHODS: In this phase IIb, double-blind, dose-ranging study, participants were randomized to receive one of eight treatments for 6 weeks: brepocitinib 0·1% once daily (QD), 0·3% QD or twice daily (BID), 1·0% QD or BID, 3·0% QD, or vehicle QD or BID. The primary endpoint was the percentage change from baseline in the Eczema Area and Severity Index (EASI) total score at week 6. Adverse events (AEs) were monitored. RESULTS: Overall, 292 participants were enrolled and randomized. The brepocitinib 1% QD and 1% BID groups achieved statistically significantly greater (with multiplicity-adjusted P < 0·05 due to Hochberg's step-up method) percentage reductions from baseline in EASI total score at week 6 [least squares mean (90% confidence interval, CI): QD: -70·1 (-82·1 to -58·0); BID: -75·0 (-83·8 to -66·2)] compared with respective vehicle [QD: -44·4 (-57·3 to -31·6); BID: -47·6 (-57·5 to -37·7)]. There was not a dose-dependent trend in AE frequency, and there were no serious AEs or deaths. CONCLUSIONS: Topical brepocitinib is effective and well tolerated in participants with mild-to-moderate AD. What is already known about this topic? Janus kinase (JAK) inhibitors are in development for treatment of atopic dermatitis (AD). The tyrosine kinase 2 and JAK 1 inhibition by brepocitinib may bring a new profile for topical JAK inhibitors for treatment of mild-to-moderate AD. What does this study add? Topical brepocitinib can provide rapid, effective symptom reduction, and could offer a novel alternative to current topical treatments for mild-to-moderate AD.

Economic Burden and Healthcare Resource Use of Alopecia Areata in an Insured Population in the USA.

INTRODUCTION: Comparative data on the economic burden of alopecia areata relative to the general population are limited. The objective of this retrospective database analysis was to evaluate healthcare resource utilization and direct medical costs among patients with alopecia areata from the US payer perspective compared with matched controls. METHODS: Validated billing codes were used to identify patients with alopecia areata from the IQVIA PharMetrics Plus (2016-2018) who had continuous pharmacy and medical enrollment for 365 days both before (baseline period) and after (evaluation period) the index date. Demographic and clinical characteristics were characterized, and baseline comorbidities were assessed with the Quan Charlson Comorbidity Index. RESULTS: Using the exact matching feature from Instant Health Data, 14,340 patients with alopecia areata were matched with 42,998 control patients aged ≥ 12 years. Patients with alopecia areata had higher healthcare resource utilization and adjusted total all-cause mean medical costs versus matched controls ($8557 versus $6416; p < 0.0001), because of higher inpatient costs, emergency department visits, ambulatory visits, number of prescriptions and prescription costs, and other costs such as durable medical equipment and home healthcare. The number of inpatient visits did not significantly differ between the two groups. Mean ambulatory costs were $3640 for patients with alopecia areata and $2062 for controls, and mean pharmacy costs were $3287 and $1843, respectively (p < 0.0001 for both). Pharmacy costs related to immunologic agents represented 50.0% of the total difference in pharmacy spending between patients with alopecia areata and controls. Surgery on the integumentary system accounted for 9.5% of the total difference in ambulatory costs. CONCLUSION: Alopecia areata is associated with significant incremental healthcare resource utilization and costs relative to matched controls due to increased spending in areas such as surgical procedures and psychological and pharmacological interventions. Costs are primarily driven by ambulatory and pharmacy spending.

All-cause health care resource utilization and costs among adults with alopecia areata: A retrospective claims database study in the United States.

BACKGROUND: Alopecia areata (AA) is an autoimmune disorder characterized by hair loss. Patients may present with hair loss of the scalp, eyelashes, eyebrows, and/or body. Alopecia totalis (AT), total scalp hair loss, or alopecia universalis (AU), total body hair loss, are extensive forms. Although the impact of AA on quality of life is understood, evidence of its economic burden is limited. A better understanding of the all-cause health care costs for health plans and patients with AA is critical to comprehend disease burden. OBJECTIVE: To evaluate all-cause health care resource utilization and direct health care costs in US adults with AA with or without AT or AU, vs matched control subjects. METHODS: Patients (≥ 18 years) with AA with no less than 2 claims of AA at diagnosis (October 31, 2015, to March 3, 2018) were identified in the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental databases. Patients were enrolled no less than 12 months before and after first diagnosis (index). Patients were grouped according to AT or AU status (AT/AU group) or AA without AT/AU (non-AT/AU group) and matched 1:3 to control subjects without AA/AT/AU. Summary statistics were calculated for demographic and clinical characteristics at baseline and follow-up. RESULTS: At baseline, there were 14,972 adult patients with AA and 44,916 control subjects. Of patients with AA, 1,250 and 13,722 were in the AT/AU and non-AT/AU groups, respectively. A significantly greater proportion of patients with AA had atopic and autoimmune comorbidities vs control subjects. After index, patients with AA used significantly more corticosteroid treatments (injectable/oral/topical) than control subjects. A greater mean number of annual outpatient and dermatologist visits was observed for both AA groups vs control subjects (outpatient visits: AT/AU group: 17.8 vs 11.8; non-AT/AU group: 15.4 vs 11.2; dermatologist visits: AT/AU group: 3.4 vs 0.4; non-AT/AU group: 3.4 vs 0.4; P < 0.001 for all). Mean total all-cause medical and pharmacy costs (2018 US$) were higher in both AA groups vs control subjects (AT/AU group: $18,988 vs $11,030; non-AT/AU group: $13,686 vs $9,336; P < 0.001 for both). Patient out-of-pocket costs were higher for AA vs control subjects (AT/AU group: $2,685 vs $1,457; non-AT/AU group: $2,223 vs $1,341; P < 0.001 for both). CONCLUSIONS: Compared with control subjects, patients with AA are more likely to have atopic and autoimmune comorbidities, to use corticosteroids, and to make outpatient visits. Patients with AA have greater all-cause medical (including pharmacy) and out-of-pocket costs. The difference in total medical costs for patients with AT/AU vs control subjects is higher than the difference for patients with non-AT/AU vs control subjects. DISCLOSURES: This study was sponsored by Pfizer Inc. Pfizer Inc was involved in the study design; collection, analysis, and interpretation of data; writing of the report; and the decision to submit this report for publication. A. Mostaghimi reports consulting fees from Pfizer Inc, Concert, Lilly, AbbVie, hims, and Digital Diagnostics; reports equity from Lucid and hims; and is an associate editor at JAMA Dermatology. K. Gandhi, M. Ray, and V. Sikirica are former employees of Pfizer Inc and held stock and/or stock options with Pfizer Inc at the time of writing. N. Done, W. Gao, C. Carley, T. Wang, and E. Swallow are employees of Analysis Group, Inc, a consultancy that received payment from Pfizer Inc for participation in this analysis.

Prevalence of Vitiligo Among Adults in the United States.

IMPORTANCE: Vitiligo can have profound effects on patients and is often associated with other autoimmune comorbid conditions. It is important to understand the current prevalence of vitiligo, including diagnosed, undiagnosed, and subtypes (nonsegmental and segmental). OBJECTIVE: To estimate the point prevalence of vitiligo in the US. DESIGN, SETTING, AND PARTICIPANTS: For this population-based study of adults in the US, a cross-sectional online survey was administered between December 2019 and March 2020 to obtain participant self-reported vitiligo status. A representative sample of the US adult general population, aged 18 to 85 years, was recruited using a stratified proportional, sampling design from general population research panels. Additionally, 3 expert dermatologists adjudicated participants' self-reported vitiligo diagnosis by reviewing photographs uploaded by the participants using a teledermatology app designed and tested specifically for this study. MAIN OUTCOMES AND MEASURES: The main outcomes were the point prevalence estimates of overall vitiligo, as well as diagnosed, undiagnosed, nonsegmental, and segmental vitiligo. RESULTS: Among the 40 888 eligible adult participants, the mean (SD) age was 44.9 (17.4) years, 23 170 (56.7%) were female, 30 428 (74.4%) were White, and 4225 (10.3%) were of Hispanic, Latino, or Spanish origin. Self-reported vitiligo prevalence was 1.38% (95% CI, 1.26%-1.49%), with 0.77% (95% CI, 0.68%-0.85%) for diagnosed and 0.61% (95% CI, 0.54%-0.69%) for undiagnosed. Based on expert dermatologist review of 113 photographs of participants with self-reported vitiligo, clinician-adjudicated vitiligo prevalence (sensitivity bounds) was 0.76% (0.76%-1.11%), with 0.46% (0.46%-0.61%) for diagnosed and 0.29% (0.29%-0.50%) for undiagnosed. Self-reported nonsegmental vitiligo prevalence was 0.77% (95% CI, 0.68%-0.85%), with 0.48% (95% CI, 0.41%-0.55%) for diagnosed and 0.29% (95% CI, 0.23%-0.34%) for undiagnosed. Clinician-adjudicated nonsegmental vitiligo prevalence (sensitivity bounds) was 0.58% (0.57%-0.84%), with 0.37% (0.37%-0.49%) for diagnosed and 0.21% (0.20%-0.36%) for undiagnosed. Self-reported segmental vitiligo prevalence was 0.61% (95% CI, 0.53%-0.69%), with 0.28% (95% CI, 0.23%-0.33%) for diagnosed and 0.33% (95% CI, 0.27%-0.38%) for undiagnosed. Clinician-adjudicated segmental vitiligo prevalence (sensitivity bounds) was 0.18% (0.18%-0.27%), with 0.09% (0.09%-0.12%) for diagnosed and 0.08% (0.08%-0.15%) for undiagnosed. CONCLUSIONS AND RELEVANCE: Results of this survey study demonstrated that the current US population-based prevalence estimate of overall (diagnosed and undiagnosed combined) vitiligo in adults is between 0.76% (1.9 million cases in 2020) and 1.11% (2.8 million cases in 2020). Additionally, this study suggests that approximately 40% of adult vitiligo in the US may be undiagnosed. Future studies should be performed to confirm these findings.

Patient-Reported Symptoms and Disease Impacts in Adults With Moderate-to-Severe Atopic Dermatitis: Results From a Phase 2b Study With Abrocitinib.

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) is inadequately controlled with current treatments for many patients. Abrocitinib is an oral Janus kinase 1 selective inhibitor under investigation for the treatment of AD. OBJECTIVE: The aim of the study was to evaluate patient-reported outcomes in a phase 2b study of abrocitinib in adults with moderate-to-severe AD inadequately controlled by topical therapy (NCT02780167). METHODS: Patients (N = 267) were randomly assigned 1:1:1:1:1 to 12-week, once-daily abrocitinib (200, 100, 30, 10 mg) or placebo. Patient-reported outcomes included pruritus numeric rating scale (average), Patient Global Assessment, Patient-Oriented Eczema Measure, Pruritus and Symptoms Assessment for AD, Dermatology Life Quality Index, and Hospital Anxiety and Depression Scale (HADS). RESULTS: Abrocitinib 200 or 100 mg resulted in significantly greater improvements from baseline versus placebo in peak pruritus numeric rating scale (by days 2 and 3, respectively), Patient-Oriented Eczema Measure, Pruritus and Symptoms Assessment for AD, Dermatology Life Quality Index, and HADS (200 mg only, by week 1 or 2), and proportions of the patients with Patient Global Assessment clear/almost clear with 2-point or greater improvement (by weeks 1 and 4, respectively) that continued through week 12 (except HADS). CONCLUSIONS: Abrocitinib treatment resulted in rapid (2 days to 2 weeks) and persistent improvements in AD symptoms and impacts in moderate-to-severe disease.

Patient Perspectives of the Social, Emotional and Functional Impact of Alopecia Areata: A Systematic Literature Review.

INTRODUCTION: Alopecia areata (AA) is a chronic, autoimmune disease of hair loss, which can significantly affect the emotional and psychological well-being of patients. A systematic literature review was conducted to better understand the burden of AA from the patient perspective. METHODS: Embase, MEDLINE and Cochrane databases were searched for published studies (2008-2018) reporting on assessments of health-related quality of life (HRQoL) for patients with AA. Qualitative, and quantitative data were collected. RESULTS: The review included 37 studies encompassing a range of clinical outcome assessment (COA) tools. None of the COA tools were specific for AA, and only one study used the Hairdex scale, which was designed to evaluate HRQoL in patients with disorders of the hair and scalp. All studies reported substantial impact on HRQoL due to AA, both overall and in domains related to personality (i.e. temperament and character), emotions and social functioning. Acute stress was also noted, and several studies identified lack of emotional awareness (alexithymia) in 23-50% of the patients with AA. CONCLUSIONS: Although it is well-established that patients with AA experience anxiety and depression, they also experience a decrease in HRQoL in many other areas, including personality, emotions, behaviors and social functioning, and these changes may be accompanied by acute stress and alexithymia. There is a need to achieve consensus on a core set of measures for AA and to develop and validate AA-specific measurement tools for use in future studies, to attain a clearer understanding of the impact of AA on patients. TRIAL REGISTRATION: PROSPERO registration number; CRD42019118646.

STUDY DESIGN: We reviewed published studies to better understand how AA affected people socially, emotionally and in their day-to-day functioning. We also looked at how healthcare providers measured these social, emotional and day-to-day effects on people with AA. Our review included 37 published studies that used several evaluation tools to measure the impacts of AA. These included a variety of questionnaires that were answered by people with AA. RESULTS: The studies reported that AA negatively affected the personality, emotions, behaviors and/or social functioning of many people with AA. However, none of the evaluation tools that were used in those studies were specific for AA, and most of the evaluation tools did not include questions about the hair or scalp. CONCLUSIONS: We recommend that a group of people familiar with AA (practitioners, researchers and patients) work together to develop an evaluation tool that is designed specifically for people with AA. This evaluation tool can then be used in future studies to better understand how AA affects people socially, emotionally and in their day-to-day functioning.

Alopecia areata (AA) is a disease in which a person's immune system attacks their hair follicles, from which hairs grow, causing hair loss. Studies have shown that people with AA may have a lower quality of life, and studies have reported higher rates of depression and anxiety in people with AA than in people without AA.

Correction to: Development of a conceptual model and patient-reported outcome measures for assessing symptoms and functioning in patients with heart failure.

The article Development of a conceptual model and patient-reported outcome measures for assessing symptoms and functioning in patients with heart failure.

Costs and Treatment Patterns Among Patients with Atopic Dermatitis Using Advanced Therapies in the United States: Analysis of a Retrospective Claims Database.

INTRODUCTION: For many, atopic dermatitis (AD) is not adequately controlled with topical regimens. This analysis examined treatment using advanced therapies and associated costs. METHODS: The IQVIA Health Plan Claims data set was analyzed. Patients aged ≥ 12 years with AD who newly initiated advanced therapy after the availability of dupilumab (March 28, 2017) and had ≥ 6 months continuous enrollment before and after their first advanced therapy claim (index date) were included. Advanced therapies included dupilumab, systemic corticosteroids (SCSs), systemic immunosuppressants (SISs), and phototherapy. A multivariate regression model was used to predict annualized follow-up healthcare costs. RESULTS: In total, 1980 patients were included (61.1% female; mean age, 41.2 years [SD, 17.4]; 11.3% < 18 years). Pre-index date, 65.2% of patients used topical corticosteroids (TCSs; 40.7% and 32.1% used medium and high potency, respectively). The most common advanced therapy was SCSs (N = 1453 [73.4%]; 69.2% prednisone) followed by dupilumab (N = 265 [13.4%]), SISs (N = 99 [5.0%]; 47.5% methotrexate), and phototherapy (N = 163 [8.2%]). Of patients treated with dupilumab, SISs, and phototherapy, 17.4%, 26.3%, and 14.1%, respectively, were prescribed SCSs post-index date. Overall, 62.6% of patients initiating SCSs, 49.1% initiating dupilumab, 64.6% initiating SISs, and 36.2% initiating phototherapy were prescribed TCSs post-index date. Mean annualized total costs (SD) post-index date were $20,722 ($47,014): $11,196 ($41,549) in medical costs ($7973 [$35,133] in outpatient visit costs) and $9526 ($21,612) in pharmacy costs. Mean annualized total cost (SD) varied significantly (P < 0.05) by index treatment: dupilumab, $36,505 ($14,028); SCSs, $17,924 ($49,019); SISs, $24,762 ($47,583); phototherapy, and $17,549 ($57,238). CONCLUSIONS: Switching to combination therapy with SCSs and TCSs was common within 6 months of initiating advanced therapy in patients with AD. Patients also incurred significant pharmacy and outpatient costs. These results highlight the difficulty of managing AD with these existing treatment options.

Symptoms and impacts in anemia of chronic kidney disease.

BACKGROUND: Anemia is a frequent complication of chronic kidney disease (CKD) that negatively affects patients' health-related quality of life. METHODS: We conducted qualitative concept elicitation (CE) and cognitive debriefing (CD) interviews to assess the frequency, duration, and severity of symptoms and impacts associated with anemia of CKD and to facilitate the development of a new patient-reported outcome (PRO) measure. We interviewed 36 patients with CKD and hemoglobin levels ≥8.0 to <12.0 g/dL using a semi-structured interview guide developed specifically for this study until saturation was reached. We used MAXQDA to perform qualitative analysis of interview transcripts to determine the most relevant symptoms and impacts (based on the frequency of concept mentions) experienced by participants. RESULTS: Most participants had stage 4/5 CKD (81%) and were being treated with an erythropoietin stimulating agent (69%). Spontaneously reported symptoms included feeling tired (79%), shortness of breath (39%), and weak/lacking strength (36%). We developed the Chronic Kidney Disease and Anemia Questionnaire (CKD-AQ), which includes 23 items assessing frequency and severity of the most relevant symptoms and impacts identified by patients with anemia of CKD. The CD interviews confirmed the clarity and relevance of the concepts identified in the CE phase. CONCLUSION: The CKD-AQ is a novel PRO measure that captures the frequency and severity of the most relevant symptoms and impacts associated with anemia of CKD. Future studies will evaluate its psychometric properties and its potential utility in anemia management.

Elicitation of disease concepts in patients with diabetic foot ulcers: a qualitative study.

OBJECTIVE: To identify in-depth information directly from patients with diabetic foot ulcers (DFU) on DFU symptoms, impacts on functioning and effects on health-related quality of life (HRQoL). METHOD: Semi-structured, qualitative concept elicitation interviews were conducted with patients with DFUs (Wagner grade 1 or 2) until saturation was reached. Qualitative analysis (using MAXQDA, VERBI GmbH, Germany) of interview transcripts was conducted to identify concepts relevant to patients with DFUs, based on the frequency of mentions, and elucidate themes regarding impacts on HRQoL. RESULTS: Of the 18 participants, most were male (n=14; 78%) and 10 (56%) presented with a Wagner grade of 1. Frequently reported symptoms were pain/discomfort (n=15; 83%), weeping/discharge (n=10; 56%), bleeding (n=10; 56%) and swelling (n=8; 44%). Overall, patients reported more impacts than symptoms-wound care/treatment burden (n=14; 78%), limitations on exercise/physical activity (n=13; 72%), mobility limitations (n=12; 67%), and offloading (n=12; 67%) were the most frequently mentioned. Based on findings from the patient interviews, a draft conceptual model was developed outlining interrelationships between DFU symptoms, impacts, and HRQoL from the patient perspective. CONCLUSION: Qualitative interviews captured the breadth of disease-related concepts of direct importance to patients. The draft conceptual model developed from the analysis can help identify measures or instruments for use in assessing patient-reported symptoms or HRQoL in clinical practice and may have wider research applicability, including evaluation of treatment benefits in patients with DFUs.