Survey on the Actual Use of Topical Anti-Inflammatory Drugs Among Patients with Atopic Dermatitis

Abstract

Introduction

Atopic dermatitis (AD) is a chronic inflammatory skin condition requiring long-term management to maintain remission and prevent relapse. Appropriate use of topical anti-inflammatory medications is an important factor in improving symptoms in patients with AD. This study aimed to investigate the treatment methods for maintaining remission and application of anti-inflammatory topical therapy.

Methods

This observational study was conducted in October 2022, using medical claims data from DeSC Healthcare Inc., linked with survey data collected from users of kencom®, a health promotion application. Eligible patients were adults aged ≥ 19 years with a confirmed AD diagnosis and prescription history. The survey evaluated (1) the actual treatment situation during the remission maintenance phase; and (2) instructions, actual status and adherence for application of anti-inflammatory topical therapy.

Results

A total of 626 patients who answered the kencom® survey and met eligibility criteria were included. Of these, 42.3% were instructed to stop medication once eczema improved, while 34.2% were instructed to continue during remission. Regarding instructions for the amount applied, the most common response was “No specific instructions” (44.2%), followed by “Fingertip-unit (FTU)” (27.2%). In actual practice, “FTU” was the most common amount (42.2%). Regarding application area, the most frequent instruction and actual practice were “Apply only to areas with eczema with remaining inflammation” at 52.6% and 62.5%, respectively, followed by “Apply not only to the eczema or remaining inflamed areas but also the surrounding areas” at 24.0% and 37.2%. Regarding the application method, “Apply thinly” was the most common instruction and actual practice at 32.7% and 48.4%, respectively. Treatment adherence rates were generally high, at over 60%.

Conclusion

Guidance from healthcare professionals has a crucial role in the proper use of topical therapies for AD. It is essential to ensure that topical medications are used properly to help patients achieve their treatment goals.

Key Summary Points

Why carry out this study?

In Japan, the real-world use, patient adherence, and actual treatment practices involving anti-inflammatory topical medications during the remission maintenance phase of AD remain unclear.

The objective of this study was, therefore, to investigate the amount, area and method of application of topical anti-inflammatory atopic dermatitis medication; the treatment methods for maintaining remission (reactive or proactive); and instructions from medical institutions regarding application of topical medications; patients’ actual application practices; and adherence status.

What was learned from the study?

The impact of guidance from healthcare professionals in the topical treatment of AD is significant and appropriate patient guidance is of great importance.

It is necessary to continue to communicate to patients the proper use of topical atopic dermatitis therapies from medical facilities nationwide; and to provide guidance so that topical drugs can be used to achieve the treatment goals of patients.

Introduction

Atopic dermatitis (AD) is a disease with pruritic eczema as the main lesion that fluctuates with remissions and relapses, and requires continuous treatment of symptoms [1]. Although it generally develops in infancy and childhood and the number of patients declines with age [1], the number of patients that persist into adolescence and adulthood [2], or adult-onset AD, is also widespread [3], making it a disease of growing concern not only in children but also in young adults.

In the treatment of AD, which mainly consists of topical anti-inflammatory medication in an outpatient setting, patients and their families play the leading role in treatment. Ensuring that the patient’s family has a correct understanding of the condition and treatment and improving adherence are essential for successful treatment [1].

Treatment with anti-inflammatory topical drugs is used to maintain remission. There are two approaches to maintenance therapy during remission: proactive therapy and reactive therapy. Both involve the use of moisturisers; however, proactive therapy entails the regular application of topical anti-inflammatory agents, whereas reactive therapy involves the application of topical anti-inflammatory agents only when visible inflammation recurs. It is thought that proactive therapy can often prevent inflammation from flaring up again during the remission maintenance phase [4], but few studies have investigated the real-world use of each therapy used in Japan.

Appropriate guidance by healthcare professionals of anti-inflammatory topical medicines [5] and patient adherence to treatment [6] have been established as important factors in improving the symptoms of patients with AD. In the treatment of AD, appropriate methods have been proposed for the amount and method of application of topical anti-inflammatory drugs. For example, the recommended amount to apply is one fingertip unit. A finger-tip unit (FTU) is the amount of ointment expressed from a tube with a 5 mm diameter nozzle from the tip of the second finger to the first joint is equivalent to two palms of an adult’s hand and is the proper amount (approximately 2% of the total body surface area in adults) [7, 8]. However, there are very few studies that have investigated how instructions for the use of anti-inflammatory topical drugs for AD are provided to patients by healthcare professionals; and how these anti-inflammatory drugs are actually applied by patients across Japan (e.g. the amount applied, the method of application, etc.), and adherence to these prescribed medications.

Therefore, in this study we used data from a questionnaire survey of patients with AD and analyzed the treatment methods for maintaining remission (reactive or proactive); and instructions from medical institutions regarding application of topical medications; patients ‘ actual application practices; and adherence status.

Methods

Data Source And Study Population

The study was conducted as a fact-finding survey using the unique combination of medical claims receipt data from a health insurance association and the linked results of an online questionnaire on AD conducted among members of health insurance associations contracted by DeSC Healthcare Inc. (DeSC) (approximately 600,000 individuals), and individuals registered with the health promotion support service computer application, known as kencom^® (approximately 200,000 individuals), provided by DeSC. In the conduct of this study individuals registered with kencom^® were invited in October 2022 to participate in an on-line health questionnaire.

The target population to which the questionnaire was distributed was the health insurance association members and their families registered to kencom^Ⓡ, and this study included those who answered the questionnaire (including both people with and without AD).

In order to select the target patient population, of patients with either atopic or non-AD, for analysis the following criteria were applied.

1. Patients aged 19 to 74 years.

2. Individuals who answered “Yes” to the question “Have you been diagnosed with atopic dermatitis previously?”, and were confirmed to have a diagnosis of AD.

3. Individuals who answered “Yes” to the question “Have you experienced symptoms of AD (eczema, itching) in the past 6 months” or those who answered either “Have been treated with medicines prescribed by medical institutions” or “Have been self-treated with medicines other than those prescribed by medical institutions (OTC, alternative therapies)” in the past 6 months.

4. Individuals with AD diagnosis records (International Classification of Diseases 10th revision codes: L20, L281, L282, L309, L853, and L988) identified within 12 months before the questionnaire administration. Individuals, therefore, included not only new patients but also those who had received treatment more than 12 months prior, and were individuals who had been diagnosed with atopic dermatitis within the past 12 months and had attended visits during that period.

5. Individuals for whom prescription of anti-inflammatory topical agents (topical steroids, tacrolimus ointment, delgocitinib ointment, difamilast ointment) was confirmed in the claims data within 6 months prior to the survey response date.

The population meeting the four criteria above (n = 882) has been published by Murota et al. [2025] [9], and the present study focused on the population who were prescribed medicines for AD.

Treatment compliance was assessed by analyzing the following:

“Actual treatment situation”, “Application amount instructions and actual status“, “Application area instructions and actual status“, and “Application use instructions and actual use adherence”.

Actual Treatment Situation During the Remission Maintenance Phase

Respondents were asked the following question 1 “Have you been instructed by your doctor, nurse, pharmacist, etc., to apply anti-inflammatory ointments (other than moisturisers such as steroid ointments/creams/lotions, tacrolimus and delgocitinib ointments) only when eczema is present and to stop when it gets better?”.

Those respondents that answered “No” were asked the following Question 2 (when skin symptoms (e.g. eczema) have calmed down: remission maintenance phase) “What instructions have you received from your doctor, nurse, pharmacist, etc., regarding the frequency of application of anti-inflammatory ointments (other than moisturisers such as steroid ointments/creams/lotions, tacrolimus and delgocitinib ointments)?”, with the following response options: “Twice a day”; “Once a day”; “Once every two days”; “Once every three days”; “Twice a week”; “Once a week”; “Other, no need to apply”; and “No specific instructions”.

Application Amount Instructions and Actual Status

Respondents were asked to provide answers regarding adherence between the instructed amount of topical application and the amount actually applied by the patient using the following categories:

“FTU; about the size of 1 yen coin for the size of two palms”; “Enough to make a tissue stick to the skin”; “Enough to make the skin shiny”; “One tube for x days”; “Other; no specific instructions”; and “Unknown”. Adherence was defined as a match between the instructions and the actual amount applied. When calculating the adherence rate, the percentage was calculated by excluding “Other,” “No specific instructions,” and “Unknown” from the denominator.

Application Area Instructions and Actual Status

Respondents were asked to provide answers regarding adherence between the area instructed for topical application, and the area actually applied by the patient using the following categories: “Apply only to areas with eczema or remaining inflammation”; “Apply not only to the eczema or remaining inflamed areas, but also to the surrounding areas”; “Other; “No specific instructions”; and “Unknown”. Adherence was defined as a match between the instructions and the actual area applied. When calculating the adherence rate, the percentage was calculated by excluding “Other,” “No specific instructions,” and “Unknown” from the denominator.

Application use Instructions and Actual Status

Respondents were asked to provide answers regarding adherence between the actual instructions for application use and the application use that was followed using the following categories: “Apply as if placing it on top”; “Apply thinly”; “Apply thickly”; “Apply gently without rubbing”; “Rub in”; “Other”; “No specific instructions”; and “Unknown”. Adherence was defined as a match between the instructions for use provided and the application use followed. When calculating the adherence rate, the percentage was calculated by excluding “Other,” “No specific instructions,” and “Unknown” from the denominator.

Statistical Analysis

Summary statistics were calculated. Continuous data were presented as mean, standard deviation, quartiles, maximum and minimum values; and for categorical data the number and percentage (%) of patients in each category were presented.

Prescription intervals were calculated from the number of days between the prescription date of the drug and the next prescription date.

All available data were used, and no imputation was performed for missing data. Data were analyzed in SAS Release 9.4 (SAS Institute, Inc., NC, USA).

Ethical Approval

This study used secondary, anonymized data provided by DeSC. Therefore, no additional individual-level informed consent was obtained for conducting this study. The study protocol was approved by the Ethics Committee of Otsuka Pharmaceutical Co., Ltd. Research and Development Division, Research Ethics Committee (application and approval No: 221013). The questionnaire survey was conducted by DeSC in accordance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects in Japan and the Declaration of Helsinki. DeSC Healthcare, Inc. has granted Otsuka Pharmaceutical Co., Ltd permission to publish the data used in this manuscript, as documented in the Third-Party Disclosure / Re-use Permission Approval Document.

Results

In this study, based on the survey data of health insurance association members contracted with DeSC and registered users of the health promotion application kencom®, we evaluated the prescription status (e.g., Proactive) of topical anti-inflammatory medications during the remission maintenance phase. A total of 20,678 individuals responded to a questionnaire administered by DeSC through kencom®. Of these individuals, 626 patients with AD were identified to be prescribed topical anti-inflammatory medications (Fig. 1).

Fig.1.

Patient disposition. AD Atopic dermatitis, DeSC DeSC Healthcare Inc.

Demographics

The analysis population comprised of 346 males (55.3%), and 280 females (44.7%), showing a slightly higher proportion of males in the study population. The mean age (SD) was 45.4 (10.7) years. The mean frequency (SD) of drug prescriptions in the past year was 4.5 (4.9) prescriptions. (Table 1).

Table 1.

Patient Background: Demographics, Drugs administered, Frequency of prescriptions

	n = 626 n %
Gender
Male	346 (55.3%)
Female	280 (44.7%)
Age
Mean ± SD	45.4 ± 10.7
Topical medicine use
Tacrolimus ointment + TCS*	120 (19.2)
TCS (Very strong) only	92 (14.7)
Delgocitinib ointment + TCS	87 (13.9)
TCS (Very strong + Strong)	45 (7.2)
TCS (Very strong + Medium)	41 (6.5)
TCS Very strong—Strong—Medium	39 (6.2)
TCS (Strong only)	31 (5.0)
TCS (Strong – Medium)	20 (3.2)
TCS (Strongest—Very strong)	18 (2.9)
TCS (Strongest—Very strong – Strong)	16 (2.6)
Dupilumab	13 (2.1)
TCS (Strongest—Very strong—Strong—Medium)	12 (1.9)
TCS (Medium only)	11 (1.8)
TCS (Strongest only)	10 (1.6)
TCS (Strongest—Very strong – Medium)	10 (1.6)
Frequency of drug prescriptions (past year)	n = 617
Mean ± SD	4.5 ± 4.9
Median	3.0
min, max	1, 77
1Q, 3Q	2.0, 6.0

The following descriptions: “Very Strong”, “Strong”, “Medium”, “Strongest”, indicate the ranks of topical corticosteroids as classified in the Japanese guidelines [1]

^*TCS: Topical Corticosteroid

Actual Treatment Situation During the Remission Maintenance Phase

Regarding the “Actual treatment situation” for Question 1, 265 (42.3%) of patients answered “Yes (instructed to stop when eczema gets better)”; 214 (34.2%) answered “No (instructed to continue for a while without stopping immediately)” and 110 (17.6%) answered “No specific instructions”. Of the patients who answered “No” to Question 1, 181 (28.9% of all patients) reported applying it “Twice a day”, “Once a day”, “Once every two days”, “Once every three days”, “Twice a week” or “Once a week”. Additionally, the proportion of patients who applied anti-inflammatory topical medications “Once every two days” or less frequently was 33/626 (5.3%) (Table 2).

Table 2.

Actual treatment situation

	N = 626(%)
Question 1: Have you been instructed by your doctor, nurse pharmacist, etc., to apply anti-inflammatory ointments (other than moisturisers such as steroid ointments/creams/lotions, tacrolimus and delgocitinib ointments) only when eczema is present and to stop when it gets better?
(i) Yes (instructed to stop when eczema improves)	265	(42.3)
(ii) No (They are instructed not to stop immediately but to continue for a while)	214	(34.2)
None of these apply	27	(4.3)
No specific instructions	110	(17.6)
I don’t know	10	(1.6)
(Only for those who answered (ii) above)
Question 2: What instructions have you received from your doctor, nurse, pharmacist, etc., regarding the frequency of application of anti-inflammatory ointments (other than moisturisers such as steroid ointments/creams/lotions, tacrolimus and delgocitinib ointments)? (When skin symptoms (e.g. eczema) have calmed down: remission maintenance phase)
Twice a day	73	(11.7)
Once a day	75	(12.0)
Once every two days	10	(1.6)
Once every three days	9	(1.4)
Twice a week	6	(1.0)
Once a week	8	(1.3)
Other	2	(0.3)
No need to apply	11	(1.8)
No specific instructions	17	(2.7)
Unknown	3	(0.5)

Application Amount Instructions and Actual Status

The most common response to the “Application amount instructions” (Fig. 2) was “No specific instructions” (44.2%); followed by “FTU” (27.2%); “About the size of one yen coin for the size of two palms” (8.9%); “Enough to make a tissue stick to the skin” (5.3%); and “Enough to make the skin shiny” (3.4%). Regarding the actual status of medication application, the majority of patients (Fig. 2) reported “FTU” (42.2%); followed by “About the size of one-yen coin for the size of two palms” (16.1%); “Enough to make the skin shiny” (16.1%); and “Enough to make a tissue stick to the skin” (12.3%).

Fig. 2.

Application amount instructions and actual status, FTU Fingertip-unit

The “Adherence to application amount instructions” was analyzed in the 287 patients that were given application amount instructions (excluding patients given “No specific instructions”, “Other” and “Unknown”, to evaluate the percentage of patients that adhered to the medicine use instructions (Fig. 3). The overall adherence rate was highest for patients given “FTU” instructions (86.7%), followed by “About the size of one-yen coin for the size of two palms” (78.2%); “Enough to make skin shiny” (66.7%); and “Enough to make a tissue stick to the skin” (63.6%). The patient adherence rate was low for patients instructed use “One tube for x days” (33.3%).

Fig. 3.

Adherence to application amount instructions, FTU Fingertip-unit

Application Area Instructions and Actual Status

Regarding “Application area instructions and actual status“ (Fig. 4), the most common instruction and actual status were “Apply only to areas with eczema or remaining inflammation” (52.6% and 62.5% respectively); followed by “Apply not only to the eczema or remaining inflamed areas, but also the surrounding areas” (24.0% and 37.2% respectively). “No specific instructions” were given to 20.4% of respondents.

Fig. 4.

Application area instructions and actual status

The “Adherence to application area instructions” was analyzed in the 478 patients that were given application area instructions (excluding patients given “No specific instructions”, “Other” and “Unknown”, to evaluate the percentage of patients that adhered to the medicine area instructions (Fig. 5). Adherence rates were greater than 80% in all application area instruction categories. For “Apply to areas with eczema or remaining inflammation” the adherence rate was 85.1%; and for “Apply not only to the eczema or remaining inflamed areas, but also the surrounding areas” the adherence rate was 80.7%.

Fig. 5.

Adherence to application area instructions

Application use Instructions and Actual Status

Regarding “Application use instructions and actual use status” (Fig. 6), the instructions provided were broadly followed in actual clinical use. The application use instruction and actual use status were “Apply thinly “ at 32.7% and 48.4% respectively; “Apply gently without rubbing” at 18.7% and 25.4% respectively; “Apply as if placing it on top” at 10.2% and 11.3% respectively; “Apply thickly” at 4.2% and 5.4% respectively; and “Rub in” at 3.4% and 8.9% respectively. A total of 27.3% of patients stated that they had no specific instructions from medical institutions.

Fig. 6.

Application use instructions and actual status

The “Adherence to application use instructions” was analyzed in the 432 patients that were given application use instructions (excluding patients given “No specific instructions”, “Other” and Unknown”, to evaluate the percentage of patients that adhered to the medicine use instructions (Fig. 7). The adherence rate was greater than 60% in all application use instruction categories. For “Apply thinly” the adherence rate was 88.8%, “Apply gently without rubbing in” was 79.5%”; “Apply as if placing it on top” was 73.4%; “Rub in” was 70.0%; and “Apply thickly” was 61.5%.

Fig. 7.

Adherence to use application method instructions

Discussion

Studies have been conducted in Japan to investigate the status of providing instructions for topical medications from pharmacists to patients [10, 11], but few studies have investigated the actual status of topical medications for patients with AD on a nationwide basis.

This study, therefore, aimed to investigate the real-world prescription practices and patient adherence to topical anti-inflammatory agents during the remission maintenance phase of AD treatment.

In this study, we evaluated 626 patients who were visiting medical institutions for AD and had been prescribed topical anti-inflammatory agents. We assessed the actual prescription practices (e.g., proactive therapy), and the instructions given by medical institutions regarding dosage amount, application area, and method (“instructions”), and compared them with patients’ actual application behaviors (“actual practice”) and adherence status. The most common type of treatment is reactive therapy, which means stopping the treatment once the eczema improves.

In our study results the majority of cases were those in which the treatment was stopped once the eczema improved, which is generally referred to as reactive treatment. Only about 5% of cases were administered intermittently during the remission maintenance period, which is generally considered to be proactive in the guidelines. There were 11 patients (1.8%) who answered “No” to Question 1 and inconsistently answered that they did not need to apply medication during the remission maintenance phase, which may limit the possibility that the intention of the question was not clearly communicated. Proactive therapy during the remission maintenance phase is considered effective in reducing the recurrence of dermatitis and achieving complete remission, as suggested in previous studies [4, 12–14]. Furthermore, its efficacy has been demonstrated in several randomized controlled trials (RCTs) [15–18]. In a Japanese clinical trial, proactive therapy significantly reduced both the SCORing Atopic Dermatitis (SCORAD) index, which reflects the severity of AD, and the Dermatology Life Quality Index (DLQI), a measure of skin-related quality of life, compared with reactive therapy [18]. However, the results of this study suggest that proactive therapy has not yet been widely adopted in the treatment of AD. Of note, in Japan, topical corticosteroids prescribed by physicians are, in principle, covered by the national health insurance system, whether used for proactive or reactive therapy. Patients are usually responsible for copayment of approximately 30%, with the remaining medical expenses covered by insurance. Therefore, we consider that the low prevalence of proactive therapy is likely to be unrelated to insurance coverage. At present, patients in remission tend to reduce the frequency of outpatient visits for treatment. Because proactive therapy requires regular outpatient visits even after clinical improvement, the proportion of patients receiving it is expected to be low. We believe it is essential to further communicate the importance of proactive therapy, strengthen education, and promote its wider adoption, with the goal of providing better treatment for patients.

As for instructions from medical professionals (doctors, nurses, pharmacists, etc.), for the amount of medication applied, the most common response was “No specific instructions” at 44.2% (Fig. 2), but the amount of application indicated was “FTU” [7, 8] (as described in the Japanese guidelines[1]), “Enough to make skin shiny” and “Enough to make a tissue stick to the skin”, in that order, and for those patients for whom instructions were given, approximately 50% were considered to have received appropriate instructions. Of note, these instructions are intended for healthcare professionals, including doctors, nurses and pharmacists.

The most common amount of anti-inflammatory topical medication actually applied, in the clinical situation where patients conducted self-application was by “FTU” [7, 8], followed by “Enough to make skin shiny”; and “Enough to make a tissue stick to the skin “, and the majority of patients used the appropriate amount of medication, with a combined rate of approximately 70%. Despite “No specific instructions” being the most common instruction. The fact that FTU [19], which is considered the appropriate dosage, is the most frequently used suggests that patients are applying the correct amount based on information from external sources.

Regarding the application area of topical anti-inflammatory drugs, in both of these, “Apply not only to the eczema or remaining inflamed areas, but also to the surrounding areas” considered an appropriate application area was less common than “Apply only to areas with eczema or remaining inflammation”. Regarding the application use method, “Apply thinly” (Fig. 6) was the most common method of application in both instructions provided and the actual status, while the more appropriate methods of application “Apply as if applying it on top” and “Apply gently without rubbing” [10] were relatively rare. These findings highlight the challenges of patient guidance in the medical field. A previous survey study of pharmacists [11] found that approximately 40% of those prescribing steroids to patients with AD were instructed to “Apply thinly”, and in the future, it is important to communicate appropriate topical application medical practice guidance to patients from medical professionals, including doctors.

The results of the present study showed a trend towards high adherence rates with instructions for the amount, area and method of application of topical anti-inflammatory drugs in patients with AD, with adherence rate of more than 70% in all but a few patients. Adherence with treatment is a very important factor in the longevity of topical treatment for AD [6], suggesting that patients are highly aware of their treatment. In a 2019 survey more than 80% of pharmacy department pharmacists, acknowledged the importance of the topical steroid amount applied. As these results demonstrate, although such practices are generally recognized as necessary in Japan, education on treatment among dermatologists and other healthcare professionals in clinical settings remains insufficient. With regard to patient education, it will be essential to continue providing practical instruction on methods of topical application, and to make use of simple, user-friendly tools that can effectively explain application techniques.

In the instructions for each application, “No specific instructions” (Figs. 2, 4, 6) for the amount, area and method of application, each of these figures was consistently slightly higher than 20.0%, indicating a lack of communication between medical professionals (doctors, pharmacists, nurses, etc.) and patients. However, one possible reason why many patients reported that they had “received no instructions” may be that, although healthcare professionals did provide guidance, it was not communicated to patients in a manner that was clearly understood. This finding suggests that providing accurate and appropriately frequent instructions on topical application is essential for long-term disease management and, through improved symptom control, can also contribute to enhanced quality of life (QOL). We consider these data to represent a valuable study that elucidates the current situation in this area. Based on this fact, and to raise awareness among specialists, it is important, although such initiatives have already begun in Japan, to further establish instruction groups within dermatology-related societies and to implement correct application guidance in each region. Accordingly, we believe that providing patients with appropriate guidance and building a good relationship between healthcare professionals and patients will help reduce the proportion of cases with ‘no specific instructions’.

The results of this study suggest that although a high percentage of patients complied with instructions, that includes information that is not necessarily appropriate, which suggests that information provided by healthcare professionals has a large influence on topical therapy for AD, and that appropriate patient guidance is important. It was also found that proactive therapy during the remission maintenance phase has not yet become widespread in the treatment of AD and is not commonly recommended. Possible reasons for the reported lack of instructions include that guidance provided by healthcare professionals is not communicated accurately to patients, that healthcare professionals are too busy to provide proper instructions on topical application, or that they themselves are uncertain of the correct application method. To address these issues, it may be useful to establish dedicated instruction groups for healthcare professionals, where correct application techniques can be taught through demonstrations or videos, and to raise awareness of the possibility that patients may not have fully understood the instructions given. In order to achieve the AD treatment goal of “No interference with daily life” [1] through long-term continuation of topical therapy, it is considered essential to raise awareness of the appropriate application of topical medications in healthcare settings and provide appropriate guidance on treatment for the remission maintenance period.

Limitations

This study has limitations. First, individuals included in this study were members of employment-based health insurance associations under contract with DeSC and their families, and those who voluntarily responded to a questionnaire. These individuals may be highly health conscious, taking positive health actions in their daily lives, and this may, therefore, introduce selection bias, which in turn limits the generalizability of our findings to the Japanese population.

Second, the self-reported questionnaire responses were subject to self-report bias and recall bias due to reporting treatments received within the past 6 months.

Third, The choice between reactive and proactive approaches should be based primarily on the clinical course, and not all patients are suitable candidates from proactive treatment.

Nonetheless, the strengths of the study include the new design of the study in combining receipt data from a health insurance association and the linked results of an online questionnaire; and the relatively large sample size.

Conclusion

This study with a new methodological approach investigated the actual status of use and application of anti-inflammatory topical drugs in patients with AD in a comprehensive nationwide survey.

This finding suggests that providing accurate and appropriately frequent instructions on topical application can contribute to long-term disease management, improvement in symptoms, and thus enhancement of quality of life (QOL). We consider these data to be valuable to elucidate the current situation in this area. A dermatology-related academic society has established an instructive group for healthcare professionals, and initiated initiatives to educate them on the proper topical application method in patients with AD.

Author Contributions

Conceptualization: Takeshi Nakahara, Hiroyuki Murota, Shinichi Noto, Miyuki Matsukawa, Rikiya Toda, Yasuhito Konishi, and Daisaku Michikami; Methodology: Takeshi Nakahara, Hiroyuki Murota, Shinichi Noto, and Miyuki Matsukawa; Formal analysis and investigation: Takeshi Nakahara, Hiroyuki Murota, Shinichi Noto, Miyuki Matsukawa, and Rikiya Toda; Writing—original draft preparation: Takeshi Nakahara, Hiroyuki Murota, Shinichi Noto, Miyuki Matsukawa, Rikiya Toda, Yasuhito Konishi, and Daisaku Michikami; and Writing—review and editing: Takeshi Nakahara, Hiroyuki Murota, Shinichi Noto, Miyuki Matsukawa, Rikiya Toda, Yasuhito Konishi, and Daisaku Michikami.

Funding

This work was funded by Otsuka Pharmaceutical Co., Ltd. The funder was involved with the study design, collection, analysis, interpretation of data, and the writing of this article. Otsuka Pharmaceutical Co., Ltd, is also funding the journal’s Rapid Service Fee.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of Interest

Hiroyuki Murota has received consulting fees and/or speaker honoraria from Maruho Co., Ltd., Sanofi K.K., Pfizer Japan Inc., Torii Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., AbbVie GK, and Otsuka Pharmaceutical Co., Ltd. Takeshi Nakahara has received consulting fees and/or speaker honoraria from Mitsubishi Tanabe Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, Maruho, Sanofi, AbbVie, Eli Lilly Japan, Sun Pharma and Otsuka Pharmaceutical. Shinichi Noto has received speaker honoraria from Otsuka Pharmaceutical. Miyuki Matsukawa, Yasuhito Konishi, Daisaku Michikami, and Rikiya Toda are employees of Otsuka Pharmaceutical Co., Ltd.

Ethical Approval

This study used secondary, anonymized data provided by DeSC. Therefore, no additional individual-level informed consent was obtained for conducting this study. The study protocol was approved by the Ethics Committee of Otsuka Pharmaceutical Co., Ltd. Research and Development Division, Research Ethics Committee (application and approval No: 221013). The questionnaire survey was conducted by DeSC in accordance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects in Japan and the Declaration of Helsinki. DeSC Healthcare, Inc. has granted Otsuka Pharmaceutical Co., Ltd permission to publish the data used in this manuscript, as documented in the Third-Party Disclosure / Re-use Permission Approval Document.