Economic burden of alopecia areata: A study of direct and indirect cost in Japan using real‐world data

Alopecia area (AA) is a common autoimmune disorder, characterized by hair loss. Although its impact on quality of life is fairly well understood, studies on the economic impact of AA are limited. The aim of this study was to quantify the personal and nationwide economic burden of AA in Japan. Data were drawn from the Adelphi AA Disease Specific Programme (DSP)™, a real‐world, cross‐sectional survey with retrospective data collection, of Japanese physicians and patients with AA. The study was conducted in 2021, before the approval of Janus kinase inhibitors for AA. Physicians and their consulting AA patients completed questionnaires regarding disease severity, treatment, and AA‐related costs. The Work Productivity and Activity Impairment questionnaire was used to evaluate the impact of AA on patients' work and activity. Nationwide estimates of cost and productivity loss were extrapolated from collected patient data. A total of 50 physicians provided data on 235 patients; 58.7% were female, mean ± SD age was 41.1 ± 11.8 years, and mean physician‐estimated scalp hair loss was 40.4% ± 30.2%. Prescription medication use was high (92.3% of patients), but the use of over‐the‐counter medication was low, at 8.7%. Mean cost to patients for medication was ¥ 4263 (US$ 32.42) per month. Productivity while at work (presenteeism) was significantly impaired (23.9% ± 25.7%), but absenteeism was low (0.9% ± 2.8%). The total nationwide cost of AA was estimated at 112.7 billion yen (US$ 857 million), of which 88.1 billion yen (78.2%) was due to productivity loss. Over 2 million days per year of activity time were estimated to be lost due to AA. Thus, despite not being a physically limiting disease, AA has a significant impact in terms of cost and time, both on a personal and national level. These data highlight the need for more targeted interventions to reduce the effects of AA on the Japanese economy.

HRQoL experienced by patients with AA is similar to that seen in patients with other chronic skin diseases including atopic dermatitis and psoriasis. 5,6Patients with AA report a high incidence of stress and low self-esteem, 7 and the disease is associated with high levels of anxiety and depression. 5,8,9Systemic autoimmune/allergic diseases, including thyroid disease, vitiligo, and atopic dermatitis, may also be associated with AA. 10,11 Recently, the Japanese AA population was reported to have lower HRQoL scores compared with Japanese population norms (i.e., national standard values for Japanese), especially for psychological components, and the presence of comorbidities further decreased the HRQoL of patients with AA. 5 Current treatment options for AA are limited, 1,12,13 with the most commonly used treatment being topical corticosteroids. 3,14In 2017, the Japanese Dermatological Association (JDA) updated its AA management guidelines and ranked local steroid injections, topical corticosteroids, and topical immunotherapies as level B (recommended to perform), based on a systematic literature search. 15Topical immunotherapy with squaric acid dibutylester (SADBE) or diphenylcyclopropenone (DPCP) has been demonstrated to be an effective treatment for AA, 16 but it is not covered by health insurance in Japan.The recommendation levels for other treatment options are C1 (can be considered for use) or C2 (not recommended for use), 15 indicating a lack of efficacious treatment options.New therapies are under development for AA 17 and a Janus kinase inhibitor, baricitinib, was approved in Japan for use in severe AA in 2022. 18veral studies have addressed both overall health-care costs and out of pocket (OOP) costs of those with AA in the United States.
5][26] The majority of US patients surveyed rated their financial burden as moderate or serious. 24However, the impact on patients and the wider society goes beyond the direct health-care cost as AA can impact on all aspects of personal life, finances, and may lead to significant productivity losses. 27,28th the costs to patients likely to increase as new treatments are approved, it is important to assess the overall financial impact of AA on the individual as well as the nation.To the best of our knowledge, few studies have estimated the economic burden due to AA in Japan.The objective of this study was, therefore, to investigate the personal economic burden of AA -including the cost of productivity loss -and estimate its burden at the national level in Japan by analyzing a real-world, cross-sectional survey of JDA board-certificated dermatologists and their consulting patients with AA.

| Study design
Data were drawn from the Adelphi Alopecia Areata Disease Specific Programme (DSP)™, a cross-sectional survey with elements of retrospective data analysis of dermatologists and their consulting patients, conducted in Japan between January and March 2021.0][31] The AA DSP was submitted to the Western International Review Board (protocol number AG8446) and an exemption from ethical approval was granted.
Each survey was performed in full accordance with relevant legislation at the time of data collection, including the declaration of Helsinki and the US Health Insurance Portability and Accountability Act 1996. 32 be eligible, physicians had to be JDA board-certified dermatologists and personally responsible for the drug management for at least three patients with AA per month.One of these patients was required to have mild AA, and at least one was required to have severe AA based on the physician's subjective assessment of disease severity (i.e., mild, moderate, or severe).All other patients included were required to have either moderate or severe AA at the time of consultation.Physicians were recruited by a local fieldwork agency and their eligibility was confirmed based on the criteria described above.
Patients whose physician completed a questionnaire were then invited to voluntarily complete a survey at the time of consultation.
Patients were eligible for inclusion if they were aged 15 years or older, had a physician-confirmed diagnosis of ongoing AA and were not participating in an AA clinical trial at the time of survey.

| Physician reported data
Following recruitment, physicians were asked to provide data for their next three to 10 consecutively consulting patients with AA.
Physicians completed a questionnaire that included patient demographics and scalp hair loss range.

| Patient reported data
Patients were asked about the financial burden of their prescription AA medication, use and cost of their over-the-counter (OTC) medication, and use and cost of wigs.Costs are reported in Japanese yen, with conversions to US dollars based on 2022 average exchange rates (1US$ = ¥ 131.498). 33Patients reported on their daily productivity and activities of the 7 days prior to the survey through the Work Productivity and Activity Impairment questionnaire (WPAI) (http://www.reillyasso ciates.net/Index.html). 34The WPAI measures impairment over the last 7 days in four domains: absenteeism (work time missed), presenteeism (impairment at work/ reduced on-the-job effectiveness), work productivity loss (overall work impairment), and activity impairment (regular activities other than work).Those in employment reported on all four domains and all patients reported on the activity impairment domain.Scores range from 0 to 100 and are expressed as impairment percentages, with higher scores indicating greater impairment.Individual costs of productivity losses were estimated by multiplying the mean percentage of the overall work impairment score from the WPAI and nationwide figures for wages. 35Individual time losses for daily activities were estimated by multiplying the mean percentage of the overall work impairment score and nationwide figures for time spent in activities such as house related work, schoolwork, sports, and social life. 36

| Nationwide estimation
For nationwide estimates of medication costs, OTC medication costs, wig costs, income loss, and time loss, the AA DSP data was weighted prior to analysis so that the sample was representative of population figures for age, sex, AA prevalence, severity distribution, and employment status.The data used for nationwide estimates are listed in Table S1.Population figures were taken from the Japanese 2020 Population Census 37 and AA prevalence and severity figures were taken from recent Japanese studies. 3,5Self-pay rate for prescribed medication was assumed to be 30% of total medication costs, the norm for residents under 70 years of age in Japan. 38The participation rates of each daily activity were taken from Statistics Bureau of Japan data. 36

| Statistical analysis
Data analysis was descriptive, no statistical testing took place.
For continuous variables, mean and standard deviation are presented; for categorical variables, patient number and percentage are reported.Missing data were not imputed, therefore, the base of patients for analysis could vary from variable to variable and is reported separately for each analysis.All analyses were performed using Stata 17.0 (StataCorp LP).

| Work and activity impairments
Table 3 shows low levels of absenteeism with a mean score of 0.9 ± 2.8% across all patients in employment.Mean presenteeism was 23.9 ± 25.7%, ranging from 13.9 ± 20.5% in those with <25% hair loss to 31.4% ± 25.9% in those with over 50% hair loss.The

| Economic burden at the national level
Extrapolating these per-patient costs to the overall population in Japan suggests an estimated total annual cost of ¥112.7 billion (US$ 857 million, Table 5).The majority of this (78.2%)was due to productivity losses (¥88.1 billion) largely associated with presenteeism, with the cost of medication being the other significant contributor (20.3%).

| Activity time losses at the national level
Using the data on individual activity time losses to estimate the overall loss of activity time due to AA in Japan (

| DISCUSS ION
Although AA is a common dermatological condition, information on its financial impact in Japan is limited.This is the first study to evaluate the economic burden, including the cost of productivity losses, in patients with AA based on real-world data derived from a representative cohort of Japanese physicians and patients.The annual burden was estimated as ¥112.dermatitis, where 69.7% of the overall financial burden was due to productivity loss, although the overall burden is higher (¥3036.9billion/year). 39Productivity loss was markedly different between severity groups, with those with 25%-100% hair loss reporting twice the productivity losses of those with less than 25% hair loss.These findings suggest the importance of achieving less than 25% hair loss as a recommended treatment threshold.This correlates with the JDA guidelines which define patients with 25%-100% scalp hair loss as severe, 15 and with qualitative interviews conducted with dermatologists and patients with AA.These suggested that achieving 20% or less scalp hair loss represented treatment success among patients with 50% or more scalp hair loss. 40e majority of patients in this study were receiving prescription medication.It is possible this high rate is due to the patients being recruited at specialist visits, resulting in a higher likelihood of receiving prescription medication.However, not all those seeing a specialist received medication, which is in line with current JDA guidelines, 15 where "use of wig" and "no treatment" are recommended as level B (recommended to perform) and C1 (can be considered for use), respectively.One third of patients in this study reported using a wig now or in the past.However, the mean cost per wig was relatively low (¥ 57 263/wig).This might be due to fact that wigs for AA are not publicly subsidized in Japan.As the costs of medical wigs may be substantial, patients may instead be buying fashion wigs from nonmedical markets, for instance through online channels, to save costs.
5][26] Currently recommended medication is generally low cost, leading to a low overall cost to the patient regardless of severity.
However, with the approval of the JAK inhibitor baricitinib for use in AA in 2022, 18 these costs are likely to rise soon, particularly for patients with more severe AA.
Our study found that productivity loss was largely a result of impaired productivity while at work (presenteeism) with only small losses resulting from absences from work (absenteeism).This was comparable with results found in the US. 27,283 In our study, the respective values were 0.9 ± 2.8%, 23.9 ± 25.7%, 24.3 ± 25.8%, and 35.0 ± 29.5%.Since AA is not a disease which interferes with physical activity, it does not have a major impact on absenteeism.However, AA impacts HRQoL significantly, particularly in the mental health domains, 5 which possibly contributes to its significant impact on presenteeism.There are ongoing concerns in developed economies over workforce decline due to aging populations and low birth rates, especially in Japan.
Maintaining productivity by effective treatment of not only diseases that cause absenteeism, but also those that contribute to presenteeism, such as AA, is essential to addressing these concerns.
Beyond the financial costs and productivity loss, patients in our study showed significant activity time losses across a range of activities due to AA, particularly those with a more severe disease.This represents an additional cost beyond the direct costs assessed in this study.For instance, poor school attendance may result in a loss of educational and job opportunities and thereby negatively impact lifetime income. 25These results suggest there are many patients with AA who do not see a specialist.When the full patient population considered, the of in Japan is likely to be significantly higher than our figure of ¥112.7 billion year.
The methodology used in this study has several limitations.In conclusion, our data demonstrated a high economic burden on patients in Japan with AA, of which 78.2% was due to the costs of productivity loss.The productivity loss score was markedly different between patients with less than 25% hair loss and 25-100% hair loss.Considering the active treatment, it is important to control hair loss to a range of less than 25%.The current study provides evidence on which to base targeted interventions to minimize these effects.

ACK N OWLED G M ENTS
phototherapy therapy costs, or the cost of transportation to the hospital were out of the scope of this study.As data were collected in 2021, no patient was prescribed baricinib for AA.In addition, the COVID-19 pandemic may have influenced patient adherence and

Table 6
), the estimated time loss for house-related work (housework, caring or nursing, child care, and shopping) was 1 716 990 days/year.The majority of this (1 500 175 days/year) was in female patients.The total lost time for schoolwork, sports, and social life were 382 675, 90 103, and 121 808 days/year, respectively.TableS1shows the estimated time losses for daily activities by patient age.
Patient-reported mean annual costs.
7 billion (US$ 857 million), of which ¥88.1 billion (78.2%) was due to productivity loss (overall work impairment).This proportion is comparable to estimates for atopicTA B L E 2Abbreviations: OTC, Over the counter; SD, standard deviation.a Patients not reporting any costs were excluded from the analysis.
Impact of alopecia areata on work and general activities.Individual annual work productivity loss costs.
Our study assessed the population of patients with AA who visited hospital, and costs were extrapolated from this.Recently, a Data from patients in employment.bDatafrom all patients.TA B L E 3 a Average wage is different between regular and non-regular workers.
Estimated nationwide activity time loss.World for analyzing the database.Medical writing support under the guidance of the authors was provided by Niels Haan of Adelphi Real World, in accordance with Good Publication Practice (GPP3) M.O.reports lecture fees from Eli Lilly Japan, advisory fees from Eli Lilly Japan, Pfizer Japan Inc., Maruho Co., Bristol Myers Squibb Japan, Taisho Pharmaceutical Co., AbbVie GK and RHOTO Pharmaceutical Co., and research grants not related to the submitted work from Maruho Co., Shiseido Co., Advantest Corp., and Sun Pharma Japan Ltd. K.K. A.Y., and M.Y. are employees of Pfizer Japan Inc. and stakeholders of Pfizer Inc. P.A. and G.M. are employees of Adelphi Real World.
companies of which one was Pfizer Inc. Pfizer Inc. and Pfizer Japan Inc. did not influence the original survey through either contribution to the design of questionnaires or data collection.Data analysis and medical writing support for the present study were provided by Adelphi Real World and funded by Pfizer Japan Inc.The authors thank James Pike, James Piercy, and Jenny Austin of Adelphi RealR E FE R E N C E S