Relationship between patient acceptable symptom state and disease scores in psoriasis

Patient acceptable symptom state (PASS) is a patient‐reported outcome that reflects patients’ perspective well. The relationship between the PASS and disease scores in psoriasis has not been described. The aim of the present study was to investigate the association of PASS with Psoriasis Area and Severity Index (PASI) and body surface area (BSA) affected by lesions in patients with psoriasis. A sectional study was conducted. PASS was evaluated by a binary question on the patient’s feeling that they have about their symptoms. Clinical data including PASI, BSA, and other patient characteristics were collected. Logistic regression was used to investigate the associations. Receiver–operator curve (ROC) analysis was utilized to determine the PASI/BSA thresholds for PASS. A total of 198 participants (27.8% female, mean age 41.9 ± 12.6 years, mean disease duration 10.2 ± 8.6 years) completed this study. Of patients with mild psoriasis, 71.4% based on PASI and 76.3% based on BSA considered their symptom state acceptable. Female sex (adjusted odds ratio [OR] = 0.47; 95% confidence interval [CI = 0.42–0.92) and patients with exposed skin involved (adjusted OR = 0.38; 95% CI = 0.19–0.76) were less likely to report acceptable symptom state. The threshold for differentiating psoriasis patients in PASS was 3.85 (area under the curve [AUC], 0.67; sensitivity, 0.67; specificity, 0.60) for PASI and 2.85% (AUC, 0.66; sensitivity, 0.79; specificity, 0.54) for BSA, respectively. These results showed that mild psoriasis based on PASI/BSA score align well with PASS status. Female and exposed skin involved are risk factors for acceptable status. Both PASI and BSA have limited capability in differentiating acceptable symptom state in psoriasis.


| INTRODUC TI ON
Psoriasis is a common chronic, immune-mediated inflammatory skin disease characterized by red and scaly plaques with significantly negative impact on quality of life of patients, affecting over 125 million people globally. [1][2][3] Psoriasis Area and Severity Index (PASI) based on severity and area of psoriatic lesions is a common tool to assess the severity of psoriasis. 4 The body surface area (BSA) affected by psoriasis is another common tool that evaluates area of psoriasis lesion only. 5,6 Both tools have corresponding thresholds in differentiating the severity of disease from the clinician's perspective. Evaluation of the effectiveness of intervention in psoriasis is mostly determined by the change of PASI or BSA score from baseline. However, these changes do not necessarily represent an important improvement from the patient's perspective. Therefore, taking into consideration the patient perspective is needed to evaluate the effect of treatment in addition to the change of score. Some patient-reported measures are commonly used in psoriasis, such as the Dermatology Life Quality Index (DLQI) and EuroQol 5-Dimension (EQ-5D). [7][8][9] However, these tools focus on specific aspects of health-related quality of life (HRQoL), and these aspects do not necessarily reflect the overall impact of the disease and patient acceptability. Moreover, health utility-related measures like EQ-5D demonstrates strong ceiling effect and is not sensitive for mild disease condition.
The patient acceptable symptom state (PASS) is a patientreported measure of well-being, [10][11][12] focusing on the feelings that they have about their symptoms and representing a clinically relevant outcome. The relationship between PASS and disease activity scores or patient-reported outcomes has been evaluated in many diseases, such as ankylosing spondylitis (AS), 10,11 rheumatoid arthritis (RA), 13 and psoriatic arthritis (PsA), 14 lichen planus, 15 and scleroderma. 16,17 However, the PASS and its association with objective measures of psoriasis has not been described yet.
The objectives of the current study were to describe the PASS across different severities of psoriasis, investigate factors associated with the PASS, and determine the cut-off points of PASI and BSA for PASS.

| Study design and patients
This was a cross-sectional study in patients with psoriasis vulgaris. Patients aged 18 years and above who were admitted to the Department of Dermatology of Xiangya Hospital during September and November 2020 were consecutively enrolled. Participants who did not complete questions on the patient-reported outcomes were contacted by telephone. Informed consent was obtained from all patients before the investigation. The study followed the Declaration of Helsinki and was approved by the institutional research ethics boards of Xiangya Hospital (approval number: 2018121106).

| Data collection
The PASS was assessed by a binary answer to the following question: "Think about all the ways your psoriasis has affected you during the last 48 h. If you were to remain in the next few months as you were during the last 48 h, would this be acceptable to you?" A "yes" response to the question was considered as the achievement of the PASS (PASS-Y) and "no" corresponding to PASS-N. 14 Psoriasis Area and Severity Index and BSA affected by psoriasis were evaluated by a trained research nurse. The severity (mild, moderate, and severe) of psoriasis was determined by scores of <3, 3-10, and more than 10, respectively. Meanwhile, locations of psoriatic lesion were recorded, and if head, neck, or hands was involved, an "exposed lesion" was endorsed.
Other data collected included age, sex, psoriasis duration, education level, comorbidities (hypertension, hyperlipidemia, and diabetes), cigarette smoking, and alcohol drinking. Comorbidities were determined by medical records and self-reported history of disease. Cigarette smoking was defined as having smoked at least 100 cigarettes in one's lifetime, and alcohol drinking was defined as consumption of 30 g of alcohol per week for at least 1 year. 18 Height and weight were measured by the research nurse in a standard way.
Body mass index (BMI) was calculated as weight/squared height (kg/ m 2 ). Overweight and obesity were defined by the cut-offs of 24 and 28 kg/m 2 , respectively. 19

| Statistical analysis
Continuous variables with normal distribution were expressed as mean ± standard deviation (SD). Categorical variables were calculated and summarized as counts (percentages). Student's t-test statistic and Pearson χ 2 -test or Fisher exact test were used to analyze differences in continuous and categorical variables, respectively.
The associations of PASS with the disease scores and patients' clinical characteristics were analyzed by multivariate logistic regression with adjustments for variables of p < 0.05 in the univariate analysis. Odds ratio (OR) and 95% confidence interval (CI) were used to present the effect size of the associations. Receiver-operator curve (ROC) was used to determine the PASI/BSA thresholds for PASS based on the maximal Youden's index for sensitivity and specificity. 20 p < 0.05 was deemed statistically significant. The data were analyzed with SPSS 23 (SPSS Statistics 23; IBM).

| RE SULTS
A total of 262 patients met the inclusion criteria, and 64 refused to participate or failed to contact successfully (34 males and 30 females). Table 1 summarizes the demographic characteristics and disease characteristics of the 198 participants who completed this study. The mean age was 41.9 ± 12.6 years, 55 (27.8%) were females, and the mean psoriasis duration was 10.2 ± 8.6 years. PASI, BSA, exposed skin involved, and educational level were significantly different between PASS status. No statistical differences were found for comorbidities, smoking, alcohol drinking, and BMI between PASS status. In total, the proportion of patients who responded "yes" to the PASS was 56.6%, and 71.4% patients with mild psoriasis (defined by PASI) considered their symptom state acceptable, compared with 48% and 14% with moderate and severe psoriasis, respectively. Similarly, 76.3% patients with mild psoriasis (defined by BSA) considered their symptom state acceptable, compared with 28% and 23% with moderate and severe psoriasis, respectively.
As shown in Table 2

| DISCUSS ION
The current study brings important information on the relationship between the PASS and disease scores in psoriasis. Most patients with mild or moderate psoriasis considered their symptoms acceptable. A dose-response relationship was identified in the association between the PASS status and severity of disease. In addition, female sex and exposed skin involved were risk factors for the acceptable status. Both PASI and BSA showed limited capability in differentiating psoriasis patients in an acceptable symptom state from those not.
The clinician's and patient's perspectives could be different in terms of the severity of disease or therapeutic effect, and the discrepancy might not be conducive to the management of disease. 14,21-23 As a patient-reported measure, acceptable symptom  status, and found that females were less likely to report acceptable symptom state, and a similar result was reported in patients who underwent ligament reconstruction. 24 Exposed skin involved also considerably affected patients' acceptable symptom state in our study.
In contrast to musculoskeletal diseases such as RA and AS, psoriasis is a skin disease with evidently negative impact on appearance, and is thus more likely to cause psychological distress. [25][26][27] The degree of emphasis on smooth and beautiful skin in females is stronger than that in males. These characteristics might be the reasons why female sex and exposed skin involved are risk factors for PASS-N. Subgroup analysis also noted that the effect of exposed skin involved on PASS status was stronger as the severity increased. Patients with severe psoriasis may have larger areas of exposed skin lesion compared with moderate or mild psoriasis, as well as higher levels of systematic inflammation and metabolic disruption, resulting in effect modification statistically.
Through the ROC analyses, we determined the thresholds of PASI and BSA in differentiating PASS-Y from PASS-N as 3.95 and 2.85%, respectively. The cut-offs were within the moderate severity for PASI and mild for BSA. Previous studies reported the 75th percentile approach was also used to determine the thresholds of disease scores for PASS, 11,24 but the ROC analyses may generate a more precise estimate because thresholds defined by ROC analyses are based on the best trade-off for sensitivity and specificity. 14 Our results indicated that the PASI and BSA had limited capability in differentiating acceptable symptom state in psoriasis, and the sensitivity and specificity for both scores were lower compared with previous studies in other diseases. 13,14 This indicates that cutaneous symptoms and disfigurement may contribute to acceptability which is not captured by the objective measure of psoriasis severity.
Therefore, acceptability of patient symptoms should be taken into consideration in treatment decision-making processes in addition to the changes of PASI or BSA, and patients who report PASS-N should receive additional interventions to improve health-related outcome.
Other common patient-reported measures that are used in psoriasis include instruments for health-related quality of life, among which DLQI is the most frequently used. 7,8 However, the tool has weaknesses, such as disordered response thresholds, item bias, and psychometric properties. 28 The bio-psycho-social medical model is proposed as an integrated way to understand diseases, 29  This study has some limitations. First, selection bias might be introduced in a single-center hospital-based study that captures patients with severer disease status and stronger willingness to seek help. Second, patients may have different understanding of the single question that was used to assess the outcome. Third, more intermediate and modifiable factors for PASS should be investigated, such as psychological resilience, perceived stress, symptoms of depression and anxiety, and social support.
In conclusion, this study accentuated the importance of patientreported measures, which should be taken into consideration in treatment decision-making processes. To our knowledge, this is the first study that described PASS and investigated the association of disease severity and patient characteristics with PASS in psoriasis. We found that patients with mild psoriasis had a high proportion of acceptable status, while female sex and exposed skin involved were factors for less acceptability. Poor discrimination capability of PASI and BSA further indicates the unique value of PASS in the management of psoriasis.