Reliability and Validity of the Psoriasis Symptom Inventory in Patients With Psoriatic Arthritis

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1 Arthritis Care & Research Vol. 67, No. 12, December 2015, pp DOI /acr VC 2015, American College of Rheumatology ORIGINAL ARTICLE Reliability and Validity of the Psoriasis Symptom Inventory in Patients With Psoriatic Arthritis HILARY D. WILSON, 1 ALEX MUTEBI, 2 DENNIS A. REVICKI, 1 PHILIP J. MEASE, 3 MARK C. GENOVESE, 4 NGOZI ERONDU, 2 AJAY NIRULA, 2 FENG JING YUAN, 2 AND HEMA N. VISWANATHAN 2 Objective. To evaluate the measurement properties of the Psoriasis Symptom Inventory (PSI) in psoriatic arthritis (PsA). Methods. The PSI is an 8-item, patient-reported outcome measure of the severity of psoriasis signs and symptoms. This was a secondary analysis of pooled data from a phase II study evaluating the efficacy of brodalumab in patients with PsA. Unidimensionality and item evaluation were assessed using factor and Rasch analyses. Reliability was assessed using Cronbach s alpha (internal consistency) and intraclass correlation coefficients (ICCs) for PSI scores in patients with stable disease (test retest). Construct validity was evaluated by correlations between PSI scores and body surface area (BSA) affected by psoriasis and selected Short Form 36 (SF-36) health survey domains. Knowngroups validity was evaluated based on BSA severity categories, and the ability to detect change was evaluated based on improvement in the subject s global assessment (SGA). Results. The analysis sample (n 5 154) was 93.5% white and 63.0% female. The mean 6 SD baseline affected BSA was 10.4% %, and age was years. The PSI demonstrated unidimensionality, with good item fit and correctly ordered categories, excellent internal consistency (a ), good test retest reliability (total score ICC 0.70; item ICCs range ), convergent validity based on moderate correlations with BSA (r ), discriminant validity based on small baseline correlations (r <20.3) with the SF-36 domains (role-physical, role-emotional, vitality), known groups validity based on significant differences between BSA groups, and responsiveness based on SGA improvements (P < 0.05). Conclusion. The PSI demonstrated excellent test retest and internal consistency reliability and good construct validity in measuring psoriasis signs and symptoms severity in PsA. INTRODUCTION The Psoriasis Symptom Inventory (PSI) is an 8-item, patient-reported outcome (PRO) instrument designed to assess the severity of psoriasis signs and symptoms (1,2). The PSI was developed in accordance with the recommendations set forth by the Food and Drug Administration s (FDA) guidance on the development of PRO measures for use in medical product development to support labeling claims (3). Supported by Amgen. 1 Hilary D. Wilson, PhD, Dennis A. Revicki, PhD: Evidera, Bethesda, Maryland; 2 Alex Mutebi, PhD, Ngozi Erondu, MD, Ajay Nirula, MD, Feng Jing Yuan, MS, Hema N. Viswanathan, PhD: Amgen, Thousand Oaks, California; 3 Philip J. Mease, MD: Swedish Medical Center and University of Washington, Seattle; 4 Mark C. Genovese, MD: Stanford University, Palo Alto, California. Dr. Mutebi owns stock or stock options with Amgen. Dr. Mease has received research grants, consulting fees, and/or speaking fees (more than $10,000 each) from AbbVie, Amgen, Biogen Idec, BMS, Celgene, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex. Dr. Genovese has The guidance recommends that, for a PRO instrument to be used as an end point in clinical trials with the goal of supporting a labeling claim, its appropriateness needs to be supported by evidence demonstrating content validity, reliability, construct validity, and the ability to detect changes within the specified context of use. The content validity of the PSI was supported by saturation of concepts of psoriasis signs and symptoms based on a review of literature, input from expert clinicians and measurement experts, and evidence from concept elicitation focus groups, as well as individual interviews in patients with moderate to severe chronic plaque psoriasis (1,4). The received research grants and consulting fees (less than $10,000) from Amgen. Dr. Erondu owns stock or stock options with Amgen. Dr. Nirula owns stock or stock options with Amgen. Ms Yuan owns stock or stock options with Amgen. Dr. Viswanathan owns stock or stock options with Amgen. Address correspondence to Hilary D. Wilson, PhD, Research Scientist, Evidera, 1417 Fourth Avenue, Suite 510, Seattle, WA hilary.wilson@evidera.com. Submitted for publication December 17, 2014; accepted in revised form June 30,

2 PSI in Patients With PsA 1751 Significance & Innovations The Psoriasis Symptom Inventory (PSI) is a simple, reliable, and valid patient-reported outcome measure of psoriasis signs and symptoms severity. The PSI has also demonstrated the ability to detect change in psoriasis signs and symptoms and can be used in clinical trials and potentially in clinical practice. appropriateness of the wording, comprehension, and interpretation of the individual items and the appropriateness of the recall period were also confirmed through individual patient cognitive interviews. The PSI has demonstrated excellent internal consistency, test retest reliability, validity, and responsiveness in moderate to severe plaque psoriasis, based on a pooled analysis of data from a phase II clinical study (n 5 198) to evaluate the efficacy of brodalumab in moderate to severe chronic plaque psoriasis (2). Of the 198 patients with moderate to severe chronic plaque psoriasis included in the analysis, 23% (n 5 45) also had psoriatic arthritis (PsA), an inflammatory form of arthritis that results in pain, stiffness, and swelling in and around the affected joints and tendons (5). This distribution is consistent with prevalence estimates, which suggest that approximately 25% of patients with psoriasis also have a diagnosis of PsA (6). Psoriasis patients with comorbid PsA may be at higher risk for comorbid conditions and report a greater impaired quality of life relative to patients with psoriasis alone (7). Although 23% of patients in the previous psychometric study had comorbid PsA, this sample is too small to complete a full psychometric evaluation of the measurement properties of the PSI in patients with PsA. The objective of this study was to evaluate the measurement properties of the PSI in patients with PsA to ensure that reliability, validity, and responsiveness were acceptable in this patient population. MATERIALS AND METHODS Study patients. This was a secondary analysis of pooled data from a phase II randomized, double-blind, placebo-controlled, multiple-dose study to evaluate the safety and efficacy of brodalumab, an anti interleukin-17 receptor monoclonal antibody, in patients with active PsA (8). The phase II clinical trial involved a total of 168 patients from 29 study sites in the US and Canada, randomized to 1 of 3 treatment arms (brodalumab 140 mg or 280 mg, or placebo). To be included in the study, patients had to be between 18 and 75 years old and had to meet the diagnosis of PsA by the classification of PsA criteria (9), with at least 3 tender and at least 3 swollen joints. After randomization, primary analysis occurred at week 12 (patients entered an open-label extension after week 12 and treatment continued until study conclusion at week 264). For this analysis, selected clinician- and patientreported assessments from baseline and week 12 were used. The clinical study protocol was approved by institutional review boards, and each patient provided written informed consent prior to participating in the study. Study measures. Patient-reported assessment: PSI. The PSI consists of 8 items: itching, redness, scaling, burning, stinging, cracking, flaking, and pain (10). Patients were asked to complete the 7-day recall electronic version of the PSI by rating the severity of each symptom on a 5- point categorical rating scale, ranging from 0 5 not at all to 4 5 very severe. The PSI can use a 24-hour recall and 7- day recall, and both versions have been found to yield comparable data (11). A PSI total score is defined as the sum of all 8 items and ranges from 0 32, with higher scores indicating greater severity. Scores from baseline and week 12 were used. Patient-reported assessment: Short Form 36 (SF-36) health survey, version 2. The SF-36 is a generic, 36-item, subject-completed measure of general health status over the prior 4 weeks (scored from 0 to 100) across 8 domains: physical function, role limitations physical, bodily pain, general health perceptions, vitality, social function, role limitations emotional, and mental health (12). The SF-36 domain scores can also be summarized into the physical component summary (PCS) and mental component summary (MCS), which are norm-based scores, with a mean of 50 and an SD of 10. Higher SF-36 scores indicate better health status. SF-36 scores from baseline and week 12 were used. Subject s global assessment of disease activity (SGA). The patient s global assessment of his or her arthritis disease activity used an 11-point numerical rating scale, ranging from 0 5 no activity at all to 10 5 worst activity imaginable. Scores from baseline and week 12 were used. Clinician-reported assessments. Body surface area (BSA). The BSA is a physician-completed assessment of the proportion (percentage) of a patient s total body surface area that is involved with psoriasis (13). The BSA was assessed at baseline only. Physician global assessment of disease activity (PGA). The static version of the global assessment of the patient s arthritis was assessed on an 11-point numerical rating scale ranging from 0 5 no activity at all to 10 5 worst activity imaginable (14). Patients and physicians completed the global assessments independently from each other. Data were used from baseline and week 12 visits. Clinical Disease Activity Index (CDAI). CDAI is a composite score that is based on 28-joint count (using 28 tender and 28 swollen joints), PGA, and SGA (15). The thresholds that have been established for interpreting the CDAI are remission ( ), low activity ( ), moderate activity ( ), and high activity ( ). CDAI scores from baseline and week 12 were used. American College of Rheumatology (ACR) response criteria (ACR20, ACR50, and ACR70). An ACR20 response is defined as at least 20% improvement from baseline in both tender/painful and swollen joint counts, and a 20% improvement or more in at least 3 of the following 5 criteria: PGA, SGA, the subject s global assessment of joint pain (0 100 visual analog scale), the disability index of

3 1752 Wilson et al the Health Assessment Questionnaire disability index, and acute-phase reactant, i.e., erythrocyte sedimentation rate or C-reactive protein level, whichever has greater improvement (16). The ACR50 and ACR70 are derived similarly, but use 50% and 70% improvement thresholds, respectively. ACR responses from baseline and week 12 were used. Statistical methods. This analysis used pooled data across treatment groups for all randomized patients with baseline and week-12 PSI, SGA, and SF-36 scores (n 5 154, 92% of the study patients). Mplus (17) was used for the confirmatory factor analysis (CFA). Rasch Unidimensional Measurement Models, version 2030 (18), was used for the Rasch analysis, and SAS, version 9.2, was used for all other analyses. All statistical tests used a significance level of 0.05 unless otherwise noted. Descriptive statistics. Descriptive statistics were summarized for PROs, demographics, and baseline clinical characteristics for the study sample (mean, SD, range for quantitative variables, frequency, and percentage for categorical variables) at baseline and week 12, as available. Descriptive statistics were also summarized (number, mean, SD, range, percentage at floor, percentage at ceiling, and percentage missing) for the PSI total and item scores at baseline and week 12. CFA. A CFA was conducted to confirm the PSI was unidimensional, an assumption of the subsequent Rasch analysis. Based on previous PSI factor analyses (2), which found a single factor underlying the 8 PSI items, one model with the 8 PSI items loading on a single factor was fit to the data at baseline. The overall fit of the model was assessed using the comparative fit index (CFI; $0.90) weighted root mean square residual (WRMR) (values,1.0 are considered acceptable) (19). The 90% confidence interval for the root mean square error of approximation (RMSEA) was used to give additional confidence in the estimate. For simple models, such as the one tested here, the RMSEA may be inflated, giving the impression of poor model fit (20). Rasch analysis. To evaluate whether each item in the PSI total score exhibited well-ordered response options, we fit a Rasch model to the baseline PSI data, where the probability of a patient responding in a given category of a response scale is modeled as a logistic function of the severity of the patient s symptoms (i.e., person parameters) and difficulty of the item (i.e., item parameters). The model was assessed for both overall model fit with the overall chisquare fit statistic and individual item fit, based on threshold parameters. Reliability. Internal consistency of the PSI total score was assessed using Cronbach s coefficient alpha (21). Test retest reliability was assessed by evaluating the reproducibility of PSI total scores among patients with stable disease. Patients who had no more than a 61-point difference on the SGA in a 2-week period were defined as stable. Data from 2 different time periods were evaluated: from baseline to week 2 and from weeks 2 to 4. Intraclass correlation coefficients were calculated for PSI total scores during these time periods, and values.0.70 were considered supportive of reliability (22,23). Validity. Convergent and discriminant validity were evaluated by examining the correlations between the PSI total scores and other PRO and clinician assessments at baseline and week 12. Correlations were described based on the following standards: small,0.3, moderate , and large.0.60 (24). Moderate to large correlations were expected between PSI total scores and the convergent construct of BSA. Small correlations were expected between PSI total scores and discriminant constructs measured by the SF-36 domains of role limitations due to physical health (role-physical), role limitations due to emotions (role-emotional), and vitality at baseline. Correlations were also calculated between PSI total scores and the following scale scores for exploratory purposes: the SGA, PGA, CDAI, and remaining SF-36 scores. To evaluate known-groups validity, an analysis of variance (ANOVA) model was used with the PSI total score at baseline as the dependent variable and patients grouped by psoriasis severity, defined using BSA percentage categories (,5, 5 10,.10) at baseline. As an exploratory analysis, known groups were also defined based on arthritis disease activity using CDAI scores ( , , and ) at week 12. Post hoc pairwise comparisons were conducted for each of the ANOVA models to identify any pairwise differences across groups. Ability to detect change. The ability of the PSI to detect change was explored using SGA as an anchor because there was no skin-specific measure, other than the PSI that was administered at baseline and followup in the trial. Patients were categorized as responders or nonresponders based on the change in their SGA between baseline and week 12. Two definitions of response were explored, the first considering a $3-point ($30%) change in SGA as being a clinically important difference (25), and as a sensitivity analysis, the second considering a $5-point ($50%) change as being clinically important. Change in PSI total scores corresponding to each responder or nonresponder groups was examined and differences in scores between groups were assessed using t-tests. RESULTS Descriptive statistics. Pooled data from 154 patients with available data on the relevant PRO measures and clinician assessments at baseline and week 23 were included in the psychometric analysis of the PSI in PsA. The majority of participants were female (63.0%) and white (93.5%), with a mean 6 SD age of years, and a mean 6 SD duration of PsA of years (Table 1). Mean PRO and clinician assessment scores over time are presented in Table 2. Mean 6 SD BSA at baseline was The distribution of baseline-affected BSA scores was positively skewed: a majority of the patients (52.6%) had BSA involvement of,5%, and less than one-quarter of the patients (24.0%) had a BSA involvement of.10%. Mean 6 SD PSI total score at baseline was , and these scores improved over time to a mean 6 SD of by week 12. Other PRO scores (SF-36 and SGA) and clinician assessments of PsA (PGA, CDAI, and ACR response)

4 PSI in Patients With PsA 1753 Table 1. Patient demographic and clinical characteristics at baseline (n 5 154)* Variable Baseline Age, mean 6 SD (range) years (22 74) Sex, no. (%) Male 57 (37.0) Female 97 (63.0) Race, no. (%) White 144 (93.5) Black or African American 2 (1.3) Asian 3 (1.9) American Indian or Alaska Native 2 (1.3) Native Hawaiian or other 2 (1.3) Pacific Islander Other 1 (0.6) Duration of PsA, mean 6 SD (1 33) (range) years * PsA 5 psoriatic arthritis. also demonstrated a similar trend of improvement over the 12-week period. PSI item characteristics. The percentage of patients reporting at the floor (not at all) for the PSI items at baseline ranged from 11% (scaling) to 37% (stinging). Between 4.5% (itching, stinging, and pain) and 7.1% (redness, scaling) reported at the ceiling on PSI items at baseline. By week 12, the percentage of patients reporting at the floor ranged between 32.5% (itching) and 55.8% (pain), and at the ceiling ranged between 1.9% (redness, scaling, burning, stinging, cracking, and pain) and 2.6% (itching and flaking). Correlations among the PSI items ranged between 0.57 and 0.88 at baseline and 0.73 to 0.90 at week 12. Three pairs of PSI items were highly correlated at baseline (r. 0.80): burning and stinging (r ), flaking and scaling (r ), and stinging and pain (r ). At week 12, all item item correlations were CFA. CFA provided evidence for a good model fit (CFI 0.99). The factor loadings for each PSI item ranged from 0.89 to Consistent with previous psychometric testing of the PSI by Revicki et al (2), the strongest correlation was between the items burning and stinging (r ). When this correlation was taken into account, the WRMR met the,1.0 threshold of acceptance (0.95). Rasch analysis. The PSI items exhibited well-ordered response options, with no response option found to be overlapping. Threshold values ranged from to 5.05, indicating good coverage across the range of the severity of psoriasis signs and symptoms (Figure 1). In addition, no item demonstrated misfit to the overall PSI scale (all chi-square values P. 0.05). Reliability. Internal consistency assessment using Cronbach s alpha was excellent at baseline (a ) and week 12 (a ). The test retest reliability coefficient for the PSI total score in patients with stable disease from baseline to week 2 was 0.70, and from week 2 to week 4 was Validity. The convergent validity of the PSI as a measure of psoriasis signs and symptoms severity was supported by a priori specified moderate correlations between the PSI total scores and the BSA at baseline (r ) (Table 3). Discriminant validity was supported by weak correlations between PSI total scores and the following distally related concepts at baseline: SF-36 role-physical (r ), roleemotional (r ), and vitality (r ). Correlations Table 2. Patient-reported outcomes and clinical assessment scores at baseline and week 12* Baseline Week 12 No. Mean 6 SD No. Mean 6 SD Patient-reported outcomes SF-36 PCS MCS PSI TOTAL SGA Clinical assessments ACR response, no. (%) ACR20 53 (34.4) ACR50 18 (11.7) ACR70 6 (3.9) PGA CDAI BSA * SF-36 5 Short Form 36 health survey; PCS 5 physical component summary; MCS 5 mental component summary; PSI 5 Psoriasis Symptom Inventory; SGA 5 subject s global assessment; ACR20 5 American College of Rheumatology response criteria for 20% improvement; PGA 5 physician s global assessment; CDAI 5 Clinical Disease Activity Index; BSA 5 body surface area.

5 1754 Wilson et al Figure 1. Item map at baseline. PSI 5 Psoriasis Symptom Inventory. among the PSI scores and these distally related concepts slightly increased in magnitude at week 12, but were still generally weak (range to 20.37). Small to moderate correlations were found between the PSI total scores and the following measures at baseline and week 12: SF-36 domains of physical function (baseline: r ; week 12: r ), bodily pain (baseline: r ; week 12: r ), general health (baseline: r , week 12: r ), social function (baseline: r ; week 12: r ), mental health (baseline: r ; week 12: r ), SF-36 PCS (baseline: r ; week 12: r ), SF-36 MCS (baseline: r ; week 12: r ), PGA (baseline: r ; week 12: r ), Table 3. PSI total score correlations with SF-36, PGA, SGA, and CDAI* Baseline Week 12 BSA SF-36 scale Physical function Role-physical Bodily pain General health Vitality Social function Role-emotional Mental health PCS MCS PGA SGA CDAI * Values are the Pearson s correlation coefficients. PSI 5 Psoriasis Symptom Inventory; SF-36 5 Short Form 36 health survey; PGA 5 physician s global assessment; SGA 5 subject s global assessment; CDAI 5 Clinical Disease Activity Index; BSA 5 body surface area; PCS 5 physical component summary; MCS 5 mental component summary. P, P, P, Figure 2. Known-groups validity of the Psoriasis Symptom Inventory (PSI) total score at baseline by body surface area (BSA) percentage groups. Mean PSI total scores were significantly different among groups (P, ). Scheffe s pairwise comparisons, adjusting for multiple comparisons, indicated patients with a BSA.10 had significantly more severe PSI total scores as compared to patients with a BSA,5 (P, ) and a BSA between 5 and 10 (P, 0.01). Mean PSI total scores were not significantly different between patients with a BSA,5 and a BSA from 5 to 10 (P ). SGA (baseline: r ; week 12: r ), and the CDAI (baseline: r ; week 12: r ). Known-groups validity was assessed by comparing mean PSI total scores by BSA percentage categories (,5, 5 10,.10) measured at baseline. Mean PSI total scores were significantly different among BSA severity groups at baseline (P, 0.001) (Figure 2). PSI total scores were significantly lower in individuals in the lowest BSA percentage category (BSA,5, n 5 81), compared to those in the highest BSA percentage category (BSA.10, n 5 37; P, 0.001). The PSI total score was significantly lower in individuals in the BSA percentage category of 5 10 (n 5 36), compared to those with BSA.10 (P, 0.05). Pairwise differences were not significantly different among PSI scores between the BSA,5 and BSA 5 10 groups. In exploratory analyses of known-groups validity using week-12 data, patient groups were defined based on arthritis disease activity using the CDAI, with disease thresholds of (n 5 12), (n 5 62), and (n 5 59). The main effect for the CDAI group was significant (P, 0.001). Pairwise comparisons demonstrated that PSI total scores in the least severe CDAI group (mean 6 SD ) were significantly lower than the CDAI group with the greatest disease severity (mean 6 SD ; P, 0.01). Patients in the most severe CDAI group also had significantly higher PSI scores than those in the moderately severe group (mean 6 SD ; P, 0.05). Comparisons between least severe and moderate CDAI groups were not statistically significant. Ability to detect change. When a response was defined as an improvement in SGA of 30% at week 12, a total of 58 participants (37.7%) were classified as responders. Significantly greater change (approximately a 6-point change;

6 PSI in Patients With PsA 1755 P, 0.001) was observed in the means of PSI total scores for responders than for nonresponders (n 5 96). When a response was defined as a 50% improvement in SGA at week 12, 35 participants (22.7%) were classified as responders. Significantly greater change was observed in the means of PSI total scores for responders (P, 0.001) than for nonresponders. DISCUSSION The significant negative impact of plaque psoriasis on health-related quality of life, including psychological well-being and self-image, physical discomfort, and the limitation on participation in social activities has been well documented (26 28). Psoriasis patients with comorbid PsA are more likely to report a greater impact of itching, physical irritation/soreness, and pain symptoms, as well as a greater impact on quality of life, relative to those with only psoriasis (7). Given this impact of psoriasis on health-related quality of life, it is important to include patient-reported assessments of symptom severity in clinical trials evaluating treatment benefit in PsA. The PSI is a reliable, valid measure for assessing patientreported severity of psoriasis signs and symptoms in patients with moderate to severe plaque psoriasis (2,29). It was developed in a manner consistent with the recommendations in the recent FDA guidance on PRO instrument development (3). The PSI has been used in clinical trials evaluating the treatment benefit of brodalumab in patients with moderate to severe chronic plaque psoriasis (30) and has demonstrated the ability to detect significant responses in the Psoriasis Severity and Area Index (PASI) scores, as well as the static PGA of psoriasis (2). This is the first evaluation of the measurement properties of the PSI in a study of patients with PsA. In the current sample, patients had a much lower percentage of BSA affected by psoriasis symptoms as compared to the moderate to severe plaque psoriasis population in the previous psychometric study (2). Accordingly, the mean severity of plaque psoriasis signs and symptoms as assessed by the PSI was lower on average in the PsA population relative to the moderate to severe plaque psoriasis population. CFA and Rasch analysis both supported the unidimensionality of the 8 PSI items. Although PsA patients exhibited lower overall plaque psoriasis symptom severity, the results from the Rasch analysis indicated good item fit statistics, the response options used were appropriate, and the instrument was able to assess a good coverage of the spectrum of psoriasis signs and symptoms severity in this population. The PSI demonstrated excellent internal consistency and good evidence of test retest reliability. The construct validity of the PSI was supported through moderate correlations between the PSI and the BSA (convergent validity) and smaller correlations between the PSI and more distal measures, including the SF-36 role-emotional, social function, and vitality scales (discriminant validity). In the known-groups validity analysis, the PSI total score was able to differentiate between the lowest and highest BSA severity groups. In the exploratory analyses, the PSI did not differentiate significantly between groups with lower disease (PsA) activity scale (CDAI 0 10 and CDAI ). The PSI did, however, differentiate between patients in the lowest activity (CDAI 0 10) and highest activity (of PsA) categories (CDAI ), and patients in the moderate activity (CDAI ) and highest activity (CDAI ) categories. This may suggest that patients who experience greater impairments in arthritic activity also report more severe plaque psoriasis symptoms. However, given that the PSI is specific to psoriasis signs and symptoms, and the CDAI is a measure of arthritis disease activity, additional research is needed to evaluate the relationship between plaque psoriasis severity and PsA disease activity in general. A psoriasis severity indicator such as the PASI was not used in the clinical trial and, therefore, was not available to evaluate the ability of the PSI to detect change in patients known to have experienced a change in psoriasis clinical status. However, utilizing the SGA as a clinical indicator of overall improvement in PSA signs and symptoms in exploratory analyses, patients who experienced an improvement of 30% on the SGA had significantly greater improvement in psoriasis signs and symptoms as compared to patients who experienced less than 30% improvement in the SGA. Additional research is needed to further evaluate the responsiveness of the PSI in patients using a clinical measure specific to psoriasis severity in PsA. A potential limitation of the analysis is that the findings may not be fully generalizable to the entire PsA population, given the specific inclusion and exclusion criteria for the clinical trial. Based on the current psychometric analyses, there is evidence to support the use of the PSI in patients with active PsA. Within this patient population, the PSI has demonstrated unidimensionality, excellent internal consistency, good test retest reliability, construct validity, and the ability to detect change in the severity of psoriasis signs and symptoms in PsA patients. Based on the findings from this analysis, the PSI is a robust yet simple and practical measure of psoriasis-related signs and symptoms for use in PsA clinical trials and potentially in clinical practice. AUTHOR CONTRIBUTIONS All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Wilson had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design. Wilson, Mutebi, Revicki, Viswanathan. Acquisition of data. Mease, Genovese, Erondu, Nirula, Yuan, Viswanathan. Analysis and interpretation of data. Wilson, Mutebi, Revicki, Mease, Genovese, Erondu, Nirula, Yuan, Viswanathan. ROLE OF THE STUDY SPONSOR Amgen participated in the study design and data collection, but not in the analysis or interpretation of the data. Amgen provided review and comment on the draft manuscript, developed by Evidera. Publication of this article was contingent upon approval by Amgen.

7 1756 Wilson et al ADDITIONAL DISCLOSURE Authors Wilson and Revicki are employees of Evidera, which provides consulting and other research services to pharmaceutical and device companies. In their salaried positions, they work with a variety of companies and organizations and are precluded from receiving payment or honoraria directly from these organizations for services rendered. Evidera received funding from Amgen Inc. for their role in this project. REFERENCES 1. Bushnell DM, Martin ML, McCarrier K, Gordon K, Chiou CF, Huang X, et al. Validation of the psoriasis symptom inventory (psi), a patient-reported outcome measure to assess psoriasis symptom severity. J Dermatolog Treat 2013; 24: Revicki DA, Jin Y, Wilson HD, Chau D, Viswanathan HN. Reliability and validity of the psoriasis symptom inventory in patients with moderate-to-severe psoriasis. J Dermatolog Treat 2014;25: Food and Drug Administration. 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