Abrocitinib monotherapy in Investigator's Global Assessment nonresponders: improvement in signs and symptoms of atopic dermatitis and quality of life.

BACKGROUND: Abrocitinib, a once-daily, oral Janus kinase 1 selective inhibitor, was shown to be an effective treatment for moderate-to-severe atopic dermatitis in phase 2 b/3 monotherapy trials. METHODS: These analyses included data for Investigator's Global Assessment responder (clear [0] or almost clear [1] with ≥2-grade improvement) and nonresponder patients with moderate-to-severe atopic dermatitis who received abrocitinib (200 mg or 100 mg) or placebo in three abrocitinib monotherapy trials (phase 2 b, NCT02780167; two phase 3, NCT03349060/JADE MONO-1 and NCT03575871/JADE MONO-2). Outcomes measuring skin clearance, itch, and quality of life were evaluated. RESULTS: Both nonresponders (n = 548) and responders (n = 260) treated with abrocitinib had rapid and clinically meaningful improvement in skin clearance, itch, and quality of life compared with placebo. CONCLUSION: Patients with moderate-to-severe atopic dermatitis treated with abrocitinib who did not achieve an Investigator's Global Assessment 0/1 response at week 12 still experienced rapid, clinically meaningful improvements across several other validated measures of efficacy and quality of life. CLINICALTRIALS.GOV: NCT02780167, NCT03349060, NCT03575871.

Health Utility Scores of Atopic Dermatitis in US Adults.

BACKGROUND: The impact of atopic dermatitis (AD) on health-related quality of life and health utility in the US adult population is not well established. OBJECTIVE: To determine the health utilities and quality-adjusted life-years (QALYs) lost in adults with AD versus without AD in the US population. METHODS: A cross-sectional, population-based study of 3495 adults was performed. AD was determined using modified UK diagnostic criteria for AD. AD severity was assessed using self-reported global AD severity, the Patient-Oriented Eczema Measure, the Patient-Oriented Scoring AD, and the Patient-Oriented Scoring AD itch and sleep. Six-dimensional health state short form (SF-6D) health utility scores and total QALY loss were assessed. RESULTS: The mean SF-6D score was lower in adults with AD compared with healthy adults (0.69 [95% CI, 0.68-0.70] versus 0.79 [95% CI, 0.77-0.79]). In particular, those with moderate-to-severe AD (mean, 0.53-0.66) had similar or lower SF-6D scores compared with those with all other self-reported disorders examined, except autoimmune disorders. Adults with AD and atopic comorbidities had significantly lower SF-6D scores compared with those without atopic comorbidities. Among the 7 disorders examined, AD was associated with higher total QALY loss than autoimmune disorders, diabetes, food allergy, and heart disease in both males and females. The largest QALY loss was for moderate AD in females and mild AD in males. CONCLUSIONS: Moderate-to-severe AD is associated with significant decrements of health utility in the US population. These data illustrate the heavy societal burden of moderate and severe AD and provide important insight for prioritization of resource allocation and cost-effectiveness research.

Atopic Dermatitis in America Study: A Cross-Sectional Study Examining the Prevalence and Disease Burden of Atopic Dermatitis in the US Adult Population.

Population-based estimates on the prevalence of atopic dermatitis in adults vary widely. The objectives of this study were to determine the prevalence of atopic dermatitis in the population of the United States, the distribution of disease severity, and its impact on health-related quality of life. Among 1,278 participating adults, the prevalence (95% confidence interval) of atopic dermatitis was 7.3% (5.9-8.8). Overall, 60.1% (56.1-64.1) of participants were classified as having mild, 28.9% (25.3-32.7) as having moderate, and 11% as having severe (8.6-13.7) disease. Patients with atopic dermatitis and those with more severe disease had higher scores in the dermatology life quality index (mean [standard deviation] for AD patients = 4.71 [6.44] vs. control individuals = 0.97 [2.12]) (P < 0.001) and the hospital anxiety (mean [standard deviation] for AD patients = 7.03 [4.80] vs. control individuals = 4.73 [4.8]) and depression (mean, [standard deviation] for AD patients = 5.83 [4.54] vs. control individuals = 3.62 [3.61]) scales, indicating a worse impact on quality of life and an increased likelihood of anxiety or depression. Based on our prevalence estimates, 16.5 million adults would have a diagnosis of atopic dermatitis, with 6.6 million meeting criteria for moderate to severe disease. Our study confirms the high prevalence and disease burden of atopic dermatitis in this population.

Major Comorbidities of Atopic Dermatitis: Beyond Allergic Disorders.

The consequences of atopic dermatitis reach beyond the skin and past childhood. Patients with atopic dermatitis are at risk of developing allergic comorbidities, but less is known about the associations between atopic dermatitis and non-allergic conditions. Understanding these non-allergic comorbidities has the potential to improve patient outcomes and to help mitigate the cost and burdens associated with these conditions. Atopic dermatitis is associated with cutaneous bacterial infections, more severe forms/courses of cutaneous viral infections, and extra-cutaneous infections. Atopic dermatitis is also associated with several mental health comorbidities particularly attention-deficit hyperactivity disorder, anxiety, and depression. Data are largely inconsistent for specific cancers, but atopic dermatitis appears to protect against malignancy overall; severe long-term atopic dermatitis is associated with adult lymphomas. Atopic dermatitis may also be associated with obesity, cardiovascular disease, and autoimmune disease, particularly alopecia areata and gastrointestinal immune-mediated disorders. Although the causative mechanisms underlying these associations are poorly understood, treating physicians should be aware of associations in seeking to alleviate the burden for patients with atopic dermatitis.

Developing drugs for treatment of atopic dermatitis in children (≥3 months to <18 years of age): Draft guidance for industry.

Atopic dermatitis is the most common chronic skin disease, and it primarily affects children. Although atopic dermatitis (AD) has the highest effect on burden of skin disease, no high-level studies have defined optimal therapy for severe disease. Corticosteroids have been used to treat AD since the 1950s and remain the only systemic medication with Food and Drug Administration approval for this indication in children, despite published guidelines of care that recommend against this option. Several clinical trials with level 1 evidence have supported the use of topical treatments for mild to moderate atopic dermatitis in adults and children, but these trials have had little consistency in protocol design. Consensus recommendations will help standardize clinical development and trial design for children. The Food and Drug Administration issues guidance documents for industry as a source for "the Agency's current thinking on a particular subject." Although they are nonbinding, industry considers these documents to be the standard for clinical development and trial design. Our consensus group is the first to specifically address clinical trial design in this population. We developed a draft guidance document for industry, Developing Drugs for Treatment of Atopic Dermatitis in Children (≥3 months to <18 years of age). This draft guidance has been submitted to the Food and Drug Administration based on a provision in the Federal Register (Good Guidance Practices).

Economic Burden of Atopic Dermatitis in High-Risk Infants Receiving Cow's Milk or Partially Hydrolyzed 100% Whey-Based Formula.

OBJECTIVE: To estimate the health and economic impact of feeding partially hydrolyzed formula-whey (PHF-W) instead of standard cow's milk formula (CMF) for the first 4 months of life among US infants at high risk for developing atopic dermatitis (AD). STUDY DESIGN: A Markov model was developed integrating published data, a survey of US pediatricians, costing sources and market data, and expert opinion. Key modeled outcomes included reduction in AD risk, time spent post AD diagnosis, days without AD flare, and AD-related costs. Costs and clinical consequences were discounted at 3% annually. RESULTS: An estimated absolute 14-percentage point reduction in AD risk was calculated with the use of PHF-W compared with CMF (95% CI for difference, 3%-22%). Relative to CMF, PHF-W decreased the time spent post-AD diagnosis by 8.3 months (95% CI, 2.78-13.31) per child and increased days without AD flare by 39 days (95% CI, 13-63) per child. The AD-related, 6-year total cost estimate was $495 less (95% CI, -$813 to -$157) per child with PHF-W ($724 per child; 95% CI, $385-$1269) compared with CMF ($1219 per child; 95% CI, $741-$1824). CONCLUSION: Utilization of PHF-W in place of CMF as the initial infant formula administered to high-risk US infants not exclusively breastfed during the first 4 months of life may reduce the incidence and economic burden of AD. Broad implementation of this strategy could result in a minimum savings of $355 million per year to society.

A multiple-domain framework of clinical, economic, and patient-reported outcomes for evaluating benefits of intervention in atopic dermatitis.

Atopic dermatitis (AD) increases health care utilization, affects patient quality of life, places a burden on caregivers, decreases patient/parent productivity, and adds to health care costs. Few studies have examined the effect of specific treatment modalities across a variety of AD-related outcomes. This prospective, multicenter, open-label longitudinal study of adult and pediatric patients with moderate to severe AD was conducted to evaluate the effect of a specific therapeutic intervention on AD-related outcomes over a period of 6 months. Surveys collected physician clinical assessments and patient- and caregiver-reported data across the following domains: clinical outcome, health care utilization/costs, quality of life, physical appearance, productivity/absenteeism, and medication compliance. This study is intended to help guide future research efforts on the net costs and benefits of different interventions across a diverse set of domains and in larger populations.

The economics of topical immunomodulators for the treatment of atopic dermatitis.

Atopic dermatitis is a common, chronic, relapsing inflammatory skin disease frequently affecting infants and children. The worldwide prevalence of atopic dermatitis is estimated to be 5--20% of the paediatric population. First-line therapy has generally consisted of dry skin care, avoidance of triggers, application of topical corticosteroids, and administration of antihistamines and oral antibacterials. Topical corticosteroids improve the lesions of atopic dermatitis; however, concern on the part of physicians and patients regarding adverse effects has led to reluctance to utilise topical corticosteroids early and especially for prolonged periods. Topical immunomodulators (TIMs), including tacrolimus ointment and pimecrolimus cream, were recently introduced for the treatment of atopic dermatitis. Clinical data show that TIMs are effective in atopic dermatitis, yet do not cause the significant adverse effects associated with topical corticosteroids. Questions remain regarding the place of TIMs as a treatment for atopic dermatitis and how to use them most effectively, from both therapeutic and pharmacoeconomic standpoints. Specifically, two major issues remain unresolved: (i) how TIMs measure up to other therapies, especially topical corticosteroids; and (ii) how members of the TIM drug class compare against each other. Previous research has established that atopic dermatitis has a significant impact on quality of life (QOL) and carries a substantial economic burden. Some studies have also measured the utility of various atopic dermatitis disease states. While there is a need for further research, early economic studies provide evidence that TIMs positively affect the QOL of patients and families. In certain patients, TIMs may be cost effective and have an acceptable incremental cost utility compared with topical corticosteroids.Making cost-effectiveness comparisons between tacrolimus and pimecrolimus is challenging because there are limited head-to-head comparative data. Given currently available efficacy data, the results of one study suggest that tacrolimus may be more cost effective than pimecrolimus in paediatric patients with moderate atopic dermatitis. The full economic and QOL benefits of both agents are yet to be completely understood. The studies reviewed herein are the first to delineate the pharmacoeconomic benefits of TIMs in atopic dermatitis, and lay the foundation for future analyses. TIMs represent an exciting advance in the treatment of atopic dermatitis. Additional research will help determine the proper place of TIMs among the current array of therapeutic options for atopic dermatitis.

Look beyond financial conflicts of interest in evaluating industry-academia collaborations in burden-of-illness and outcomes research studies in dermatology.

Financial relationships exist among industry, scientific investigators, and academic medical centers. These relationships can foster research in the basic sciences, clinical trials, health economics evaluations, and other outcomes assessment studies. To govern the conduct of burden-of-illness and outcomes research studies involving collaborations between industry and academia, we propose voluntary standards related to: 1) the development of and adherence to standards for research conduct and reporting; 2) disclosure, discussion, and management of potential impacts of financial conflicts of interest; and 3) transparency in research methods and open access to study results.

Validation of expert opinion in identifying comorbidities associated with atopic dermatitis/eczema.

BACKGROUND: The use of expert opinion is widespread in economic studies of healthcare utilisation; however, few studies have attempted to assess the validity of assumptions derived from such sources. OBJECTIVE: To examine the use of such expert opinion in determining comorbidities associated with atopic dermatitis/eczema (AD/E), which were assessed as part of a recent third-party payer cost-of-illness study. DESIGN: To identify the disease-related comorbidities that would represent costs associated with AD/E, physicians on an expert panel were asked individually and then collectively to group all International Classification of Diseases, 9(th) Edition-Clinical Modification (ICD-9-CM) diagnosis codes as 'most likely', 'possibly' or 'definitely not' related to the costs of identifying and treating patients with AD/E. Claims representing $US464 million in payer reimbursements from nearly 125 000 patients with AD/E were identified within two separate claims databases (1997 values). Over 850 ICD-9-CM diagnosis codes were identified in the first-listed position from these claims. For each group of 'most likely', 'possibly' and 'definitely not' related diagnosis codes, prevalence rates were compared within AD/E and non-AD/E populations from the two historical payer claims databases. Adjusted and non-adjusted odds ratios were calculated by comparing prevalence rates between AD/E and non-AD/E patients in the same payer population. RESULTS: The mean prevalence rate of any diagnosis code in the AD/E population was 0.65 +/- 1.82% (SD) with a mean odds ratio of 1.81 +/- 0.96. Comorbidities considered by the expert panel 'most likely' to be associated with AD/E had higher prevalence rates (3.28 +/- 3.63%) and odds ratios (2.14 +/- 1.14). Comorbidities considered to be 'possibly' related to AD/E had prevalence rates and odds ratios of 3.01 +/- 5.06% and 1.84 +/- 0.82, respectively. Comorbidities considered to be 'definitely not' related to AD/E had the lowest prevalence rates (0.45 +/- 1.09%) and odds ratios (1.80 +/- 0.97). CONCLUSIONS: Comparing the result of consensus panels with actual claims histories validated the use of expert opinion in determining comorbidities associated with AD/E. Expert opinion yielded valid results in terms of identifying comorbidities that manifested frequently and disproportionately in the AD/E population. Limited statistical measurements of comorbidities would have been less specific than expert opinion. Future cost-of-illness studies should consider alternative data sources and methodologies to enhance the validity and importance of expert opinion and to corroborate their findings.

Cost-effectiveness analysis of tacrolimus ointment versus high-potency topical corticosteroids in adults with moderate to severe atopic dermatitis.

BACKGROUND: Few cost-effectiveness analyses have been conducted on topical therapies for atopic dermatitis. OBJECTIVE: We sought to compare cost-effectiveness of high-potency topical corticosteroids (HPTCs) and tacrolimus ointment for the treatment of moderate to severe atopic dermatitis for patients who are not responsive to or not well controlled with mid-potency topical corticosteroids. METHODS: A Markov model represented the cyclic nature of atopic dermatitis. Clinical outcomes were derived from published literature. "Efficacy" was defined as disease-controlled days on which patients experienced a greater than 75% improvement in their disease. Resource use and changes in management were on the basis of opinions of a physician panel; secondary treatment was an oral antibiotic with topical corticosteroids. Sensitivity analyses were conducted for all variables. RESULTS: The model was sensitive to duration of continuous treatment with HPTCs. HPTCs, when limited to 2-week treatment cycles, were associated with the highest total costs ($1682 per year) and the least efficacy (185 disease-controlled days). HPTCs in 4-week treatment intervals and tacrolimus ointment were similar in total costs and efficacy ($1317 vs $1323 for 194 vs 190 disease-controlled days, respectively). Although primary drug costs were higher for patients treated with tacrolimus ointment, patients treated with regimens of HPTCs incurred higher secondary drug costs. CONCLUSION: In the base case analyses, tacrolimus ointment was more cost-effective than HPTCs administered in 2-week treatment cycles, and similar in cost-effectiveness to 4-week cycles of HPTCs.

Cost of atopic dermatitis and eczema in the United States.

BACKGROUND: Atopic dermatitis/eczema (AD/E) is a common disease. Few studies have attempted to quantify the cost to third-party payers. OBJECTIVE: Our purpose was to identify the annual cost of medical services and prescription drugs for the treatment of AD/E to private insurance and Medicaid payers in the United States. METHODS: We used a retrospective study design employing claims data from 1997 and 1998 from a private insurer and a state Medicaid program to analyze costs incurred. Beneficiaries were considered to have AD/E if they had at least one claim in 1997 with a primary or secondary listing of 1 of 3 diagnosis codes: 691.8, other atopic dermatitis and related conditions; 692.9, contact dermatitis and other eczema when no cause is specified; or 373.3, noninfectious dermatoses of eyelid. Patients who did not meet the diagnosis criteria served as a control group in each payer for comparisons of expenditures with the AD/E group. RESULTS: Disease prevalence was 2.4% (private insurer) to 2.6% (Medicaid) of all eligible beneficiaries, and 3.5% to 4.1% of patients submitted at least one health care claim during the study period. Medicaid-insured patients used outpatient hospital visits and hospitalizations at a greater rate than did privately insured patients; neither used emergency departments extensively. The third-party payer cost of illness for AD/E ranged from $0.9 billion to $3.8 billion when projected across the total number of persons younger than 65 years insured by private insurers and Medicaid in the United States. More than one fourth of all health care costs for patients with AD/E may be attributed to AD/E and co-morbid conditions. CONCLUSIONS: Annual costs of AD/E are similar to those of other diseases such as emphysema, psoriasis, and epilepsy. Patients incur significant costs associated with AD/E and co-morbid conditions.