A discrete choice experiment on oral and injection treatment preferences among moderate‐to‐severe psoriasis patients in Japan

Long‐term psoriasis (PsO) management remains challenging. With growing variation in treatment efficacy, cost, and modes of administration, patient preferences for different treatment characteristics are not well understood. A discrete choice experiment (DCE), informed by qualitative patient interviews, was conducted to assess patient preferences for different attributes of PsO treatments; 222 adult patients with moderate‐to‐severe PsO receiving systemic therapy participated in the DCE web survey. Better long‐term efficacy and lower cost were preferred (preference weights p < 0.05). Long‐term efficacy had the highest relative importance (RI) and mode of administration was as important as the outcome attributes (efficacy and safety). Patients also preferred oral to injectable administration. In subgroup analyses by disease severity, residence, psoriatic arthritis as a comorbidity, and gender, the trends for each subgroup were the same as the overall population although the extent of RI for administration mode varied. Mode of administration was more important for patients with moderate versus severe disease, or rural versus urban residence. This DCE utilized attributes related to both oral and injectable treatment as well as a broad study population of systemic treatment users. Preferences were further stratified by patient characteristics to explore trends in different subgroups. Understanding the RI of treatment attributes and the attribute trade‐offs acceptable to patients helps inform moderate‐to‐severe PsO systemic treatments decisions.

stigma and discrimination, which is exacerbated for moderate-tosevere PsO patients as the severity of the disease can impact selfesteem negatively and contribute to greater social isolation. [8][9][10] Without any curative treatments available, symptom control is the primary goal of PsO management. 3 Treatments for PsO can be classified as topical therapies, phototherapy, oral medications, and biologic agents. The choice of treatment type depends on the severity of the disease. The majority of patients with PsO have limited lesions (body surface area <5%) that can be treated with topical therapies, whereas the minority of patients, who have moderate-tosevere PsO, may require systemic therapies including oral medications and biologics. 11,12 In Japan, such biologics have been available since 2010; 13 12 The number of patients who receive topical therapies has been in decline in recent years due to the increased availability of systemic therapy options. 12 However, in Japan, there is no treatment guideline for PsO therefore no established treatment algorithm exists. Dispensation of biologic therapy is limited to Japanese hospitals accredited to administer these specific treatments, 13 and the costs of biologics are higher than topical or oral medications. 14 For PsO treatment more broadly, patient treatment preferences are often not fully discussed in routine clinical practice, and there is a lack of understanding of patient concerns or needs. 15 The DCE approach assumes a set of attributes describing key features of treatments and the relative value of a particular treatment to an individual is a function of these attributes. This method has been utilized in multiple disease areas to quantify preferences of patients, caregivers, physicians, and other stakeholders. [16][17][18][19] In the Japanese setting, two discrete choice experiments (DCEs) have been conducted to identify important treatment attributes from the perspective of moderate-to-severe PsO patients. 20,21 However, these studies included attributes and levels only relevant to biologics and were created and selected by clinicians. Therefore, there remains a lack of evidence from real-world settings in key treatment attribute choices and preferences reflecting all systemic options, including oral medication among Japanese patients with moderate-to-severe PsO.
This study uses a DCE to assess the relative importance (RI) of attributes of both oral and biologic systemic therapies from the patient's perspective when selecting treatments for moderate-to-severe PsO.

| Development of DCE
The initial vignettes of the DCE were developed based on a review of package inserts of systemic treatments, Japanese guidance for use of biologics for PsO and relevant clinical trials, literature that discusses important PsO treatment attributes from the patient's perspective, and expert opinion. Attributes for potential vignettes included efficacy, safety, mode of administration, and cost related items ( Table 1). Characteristics of both oral medications and biologics were incorporated into the draft attributes. Ranges for levels of each potential attribute were derived from the available clinical data and new biologic and oral medications for moderateto-severe PsO.
Subsequently, interviews were conducted with patients who had moderate-to-severe PsO to facilitate attribute development. The interview participants (n = 10) were recruited using a specialized patient recruiting agency in Japan. The participants were selected if they had a clinical diagnosis of moderate-to-severe and were taking oral medications or biologics as systemic therapy. Written consent was obtained prior to all interviews. Each 1-hour, semi-structured interview consisted of two parts. Interviews were audio-recorded and recordings were transcribed, and transcripts were analyzed using ATLAS.ti software.
The first part of the interview consisted of concept elicitation to understand important attributes of PsO treatment from the patient's perspective. Patients were asked about their treatment goals, reasons for switching from previous treatments, desired changes to aspects of their current treatment, key treatment attributes and risks to be avoided. Any spontaneous reports of preferences were also noted. The second part of the interview included a cognitive debriefing where "think aloud" and "verbal probing" procedures were used to assess understanding of the DCE task, its wording, and the relevance of the initial DCE vignettes.

| Design of DCE choice tasks
A block design was implemented to construct choice tasks based on D-efficiency to maximize efficiency of the design. 22

| Participants in the DCE survey
The survey population consisted of self-reported moderate-to-severe  is sufficient for estimating reliable models, and over 100 respondents are able to provide a basis for modeling preference data. 24 Another rule of thumb suggest that the sample size required for a DCE is a function of choice tasks, number of alternatives, and number of analysis cells (largest number of levels for any attribute), which is approximately 63 in this study. 25 Therefore, our conservative estimated target sample size was n = 200-300, which was above the typical sample size of healthcare DCEs 26 and in line with the expected recruitment feasibility in the Japanese online patient panel.

| Statistical analysis
A conditional logit with dummy coding was used for the analysis of the DCE to estimate preference weights and RI. The preference weights for the attributes are presented in the same order as those TA B L E 2 Attributes and levels used in the discrete choice experiment (DCE).

Attributes Levels
Patients with a 75% or greater improvement in the extent or severity of psoriasis symptoms within 1 month of starting treatment 5% (5 out of 100 patients) 10% (

| Patient interview results
Patients spontaneously reported that effectiveness, costs, mode of administration, and safety as the most important treatment attributes, which was consistent with the draft vignettes of the DCE. Table S1 presents the concepts that patients spontaneously reported and example quotes for each concept. Most patients reported that the included attributes were relevant. Additionally, the majority of patients did not identify any attributes missing from the draft vignettes. After the review of patient responses and expert suggestions, some attributes were modified and finalized, and language used in the descriptions of attributes was updated for easier comprehension ( Table 2).

| Demographics
Of the 222 patients who participated in the survey, 71% were male and mean age was 51 (  (Table S2). More than half of the patients (64%) were biologic-naïve prior to current therapy, and 48% lived in an urban area.

| Overall DCE results
Across the overall study population, long-term efficacy was the most important attribute (RI 47%), followed by cost (RI 21%) and

| Sensitivity analysis
Sensitivity analysis was conducted excluding those who failed to select the dominant task in the rationality test. Excluding these patients did not change the overall results ( Figure 3) in level of significance and direction of effect for most levels. Only the ranking of levels within mode of administration changed with "once daily" being numerically superior to "twice daily", although there was no statistical difference.

| Severity
Preferences differed between moderate and severe patients for most treatment attributes except long-term efficacy and side effects (severe infections). Regardless of severity, long-term efficacy was the most important attribute (Figure 4a). In severe patients, the second most important attribute was short-term efficacy (RI 21%), while in moderate patients, more emphasis was placed on costs (RI 21%), mode of administration (RI 16%), and GI-related side effects (RI 9%) over improving short-term efficacy (RI 4%). Moderate patients preferred oral medications over injections (Figure 4b). However, severe patients showed no significant difference in preference between oral medications and injections. Similarly, patients with moderate PsO preferred a treatment with lower risk of GI-related side effects, but patients with severe PsO did not show any difference.
Furthermore, cost was an important attribute for moderate patients compared to severe patients. With lower cost, higher preference weight was observed among moderate patients. Severe patients had similar patterns of preference to the prior biologic exposed group and moderate patients with biologic-naïve group ( Figure S2).

| Residential area
Among patients living in non-urban areas, cost (RI 28%) was ranked as the second most important attribute followed by mode of administration (RI 16%); in contrast, the patients living in urban areas regarded GI-related side effects (RI 14%) as the most important attribute after long-term efficacy (RI 56%), followed by short-term efficacy (RI 10%; Figure 5a). Patients living in non-urban areas preferred oral medications over injections (Figure 5b). However, patients living in urban areas did not have any preference for mode of administration. Non-urban residents placed more importance on costs and had a preference for lower costs compared to urban residents.

| PsA as a comorbidity
The most reported comorbidity among those surveyed was PsA (Table 3). Patients with PsA placed more importance on side effects F I G U R E 4 Subgroup analysismoderate (n = 191) versus severe (n = 31): (a) relative importance (RI) and (b) preference weight. * denotes statistically significant preference weights compared to reference group (p < 0.05).
(a) RI is calculated as a value relative to distance between the highest and the lowest attribute levels and is ranked from highest distance to lowest. (b) Preference weights are shown on the vertical scale and describe how much each level was selected within one attribute. The order of attributes above is the same as that presented in each choice task.
In contrast, patients without PsA placed more importance on mode of administration (RI 14%) and short-term efficacy (RI 9%) compared to side effects (GI-related; RI 8%). Both patient groups, with and without PsA, preferred oral over injections, (p < 0.05 in non-PsA group; Figure 6b).

| Gender
Long-term efficacy and cost were the most important attributes among both male and female patients. However male patients placed more importance on mode of administration (RI 14%) than on short-term efficacy (RI 6%) and side effects (GI-related; RI 9%), while women placed slightly more importance on short-term efficacy (RI 13%) and side effects (GI-related; RI 12.4%) than on mode of administration (RI 11.6%; Figure 7a). In terms of preference weights, oral medication was preferred compared to injection every 12 weeks among both males and females (Figure 7b). However, among females, taking a tablet once daily was less preferred compared to tablet twice daily.

| DISCUSS ION
This study used a DCE survey to investigate PsO treatment preferences among moderate-to-severe patients in Japan in terms of efficacy, safety, mode of administration, and costs. To develop the DCE attributes and levels, this study incorporated patient perspectives from qualitative interviews, in addition to the literature review and expert input.
Long-term efficacy was consistently reported as the most important attribute across the overall study population and subgroups. Sustaining long-term efficacy also remains a challenge in the real-world setting, particularly with biologics that are susceptible to anti-drug antibody formation. 28 As patients with PsO frequently experience relapse of symptoms 29 and have difficulty in controlling their symptoms over a long period, moderate-tosevere patients may prefer treatments with long lasting efficacy over short-term efficacy. Prior studies also reported that patients valued long-term efficacy more than rapid onset of treatment efficacy. 21,30 Mode of administration was, like efficacy and safety, relatively important across the overall study population and subgroups.
F I G U R E 5 Subgroup analysis-urban (n = 106) versus non-urban (n = 116): (a) relative importance (RI) and (b) preference weight. * denotes statistically significant preference weights compared to reference group (p < 0.05). (a) RI is calculated as a value relative to distance between the highest and the lowest attribute levels and is ranked from highest distance to lowest. (b) Preference weights are shown on the vertical scale and describe how much each level was selected within one attribute. The order of attributes above is the same as that presented in each choice task.
Furthermore, patients preferred oral medication over injection, which was a consistent trend observed in other countries and therapeutic areas. 18,31,32 Preferences varied across PsO severity (moderate vs. severe), with efficacy-related attributes being the most important among severe patients, while moderate patients placed greater value on mode of administration than short-term efficacy. This is consistent with other studies; patients with moderate PsO place more importance on mode of administration and preferred oral medications over injections. 33 Preferences for treatment diverged for patients living in urban and non-urban areas, with patients living in non-urban areas preferring oral medication over injections as well as treatments with lower costs. In our study population, compared to urban areas, there was a higher proportion of patients living with PsO for more than 10 years in non-urban areas (Table S3). Economic burden of treatment for PsO may be substantial because patients often experience recurrence of symptoms, and patients with long-term PsO are likely to receive long-term treatment. In Japan, the yearly economic burden of biologics treatments was estimated to be 20 times higher than topical therapies. 34 Given the potentially high economic burden, the higher proportion of those living with the disease for a long duration in non-urban areas may have contributed to the overall strong preference for lower costs. Further research that incorporates the socioeconomic factors, duration of PsO and how they impact treatment preference is needed to explore other underlying treatment needs.
Females placed more importance on short-term efficacy than other characteristics such as mode of administration and side effect (GI-related). Compared to male PsO patients, female patients tend to be more concerned about their appearance, a factor which was associated with self-reported depressive symptoms. 35 Females reported itching 36 and stigmatization 37 more frequently than their male counterparts. These characteristics are associated with poorer quality of life and higher rates of depression among females. 36 (a) RI is calculated as a value relative to distance between the highest and the lowest attribute levels and is ranked from highest distance to lowest. (b) Preference weights are shown on the vertical scale and describe how much each level was selected within one attribute. The order of attributes above is the same as that presented in each choice task.
factors such as lifestyle differences, as well as analysis of other patient characteristics in these subgroups may provide more insight on patient preferences. Further research on the factor impacting treatment preferences for PsO is warranted. to that reported elsewhere. 40 However, the statistical significance of the preference weights in the sensitivity analysis was not different from the primary analysis results with the full sample. Lastly, the DCE's construct choice sets was based on hypothetical questions that may differ from real-world decision making. In an effort to minimize the gap between hypothetical and real-world choices, F I G U R E 7 Subgroup analysismale (n = 158) versus female (n = 64): (a) relative importance (RI) and (b) preference weight. * denotes statistically significant preference weights compared to reference group (p < 0.05). (a) RI is calculated as a value relative to distance between the highest and the lowest attribute levels and is ranked from highest distance to lowest. (b) Preference weights are shown on the vertical scale and describe how much each level was selected within one attribute. The order of attributes above is the same as that presented in each choice task.

| Strengths and limitations
qualitative patient interviews were conducted to help develop of the attributes and levels in each choice set, reflecting patient experience and relevant attributes.

| CON CLUS ION
Treatment attribute preferences of moderate-to-severe patients receiving systemic PsO treatments were assessed after utilizing patient perspectives and narratives to guide the design of this study.
This DCE employed the attributes of both oral and injection treatments and stratified preferences by disease severity and other patient characteristics. Acknowledging the high RI of long-term efficacy and preference for oral mode of administration, coupled with the differences in preference among subgroups will be important considerations when making treatment decisions for moderate-tosevere PsO patients.

DATA AVA I L A B I L I T Y S TAT E M E N T
Restrictions apply to the availability of these data, which were used under license for this study. The data that support the findings of this study are not publicly available and cannot be shared with external researchers.