Arthritis Care & Research Vol. 67, No. 2, February 2015, pp 264 –272 DOI 10.1002/acr.22401 © 2015, American College of Rheumatology

ORIGINAL ARTICLE

Factors Explaining the Discrepancy Between Physician and Patient Global Assessment of Joint and Skin Disease Activity in Psoriatic Arthritis Patients LIHI EDER,1 ARANE THAVANESWARAN,1 VINOD CHANDRAN,1 RICHARD COOK,2 DAFNA D. GLADMAN1

AND

Objective. To assess the extent and determinants of discordance in scoring between patient global assessment (PtGA) and physician global assessment (PhGA) in patients with psoriatic arthritis (PsA). Methods. A cross-sectional and longitudinal analysis of data was conducted in patients attending a large PsA clinic. The difference between PtGA and PhGA (each measured on a scale of 0 –10, with 0 indicating best status and 10 indicating worst status) reflected the discrepancy between the PtGA and PhGA of joint and skin activity and could take values from ⴚ10 (higher rating of disease activity by the patient) to 10 (higher rating of disease activity by the physician). Multivariate regression identified variables that contributed significantly to each of the outcomes. The proportion of variability of each outcome explained by each predictor was expressed by the partial R2. Results. A total of 565 patients were included in the analysis. Patients tended to score their disease worse than their physicians, with greater discordance for the joints than for the skin (mean ⴞ SD 1.68 ⴞ 2.41 PtGA–PhGA difference for joints, and 0.77 ⴞ 2.66 for skin). Fatigue accounted for 21% of the variation in the difference between PtGA and PhGA for joints. Pain (R2partial ⴝ 9%) and disability by Short Form 36 health survey (R2partial ⴝ 1.2%) were also important factors, each of which led to higher patient rating; whereas increased tender joint count (R2partial ⴝ 16%) and swollen joint count (R2partial ⴝ 1.4%) resulted in a higher physician rating of arthritis. Conclusion. Fatigue, pain, disability, and tender and swollen joint counts were the most important factors contributing to discrepancy between patient and physician assessment of joint activity.

Psoriatic arthritis (PsA) is a systemic inflammatory condition affecting the skin and the musculoskeletal system. The clinical manifestations of the disease are varied and include peripheral arthritis, spondylitis, dactylitis, and enthesitis, in addition to various clinical forms of psoriasis, psoriatic nail lesions, and other extraarticular manifestations. The different combinations of these clinical features complicate the assessment of PsA as each of these manifestations can affect physical function and quality of

life. In rheumatology, the assessment of disease activity and treatment decisions rely heavily on patient-reported outcomes in combination with the physician’s perception of disease activity. This is in contrast to other fields of medicine in which treatment decisions are based on measurable biomarkers such as blood pressure and cholesterol levels. Composite outcome measures that combine patientand physician-reported outcomes are used to guide treatment decisions and quantify treatment response in observational studies and clinical trials in PsA (1). Six core domains were recommended by the Outcome Measures in

Supported by grants from The Arthritis Society, the Canadian Institutes of Health Research, and the Krembil Foundation. Dr. Eder’s work was supported by a Canadian Institutes of Health Research Fellowship and the Krembil Foundation. Dr. Chandran’s work was supported by a Canadian Institutes of Health Research Clinical Research Initiative Fellowship and the Krembil Foundation. 1 Lihi Eder, MD, PhD, Arane Thavaneswaran, MMath, Vinod Chandran, MBBS, MD, DM, PhD, Dafna D. Gladman, MD, FRCPC: Centre for Prognosis Studies in the Rheumatic

Diseases, Toronto Western Hospital, Toronto, Ontario, Canada; 2Richard Cook, PhD: University of Waterloo, Waterloo, Ontario, Canada. Address correspondence to Dafna D. Gladman, MD, FRCPC, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, 399 Bathurst Street, 1E-410B, Toronto, Ontario, M5T 2S8, Canada. E-mail: [email protected]. Submitted for publication January 21, 2014; accepted in revised form July 8, 2014.

INTRODUCTION

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Patient–Physician Discrepancy in PsA

Significance & Innovations ●

Identifying the determinants of discordance between patient and physician global assessment can potentially improve treatment outcomes.

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Patients with psoriatic arthritis tend to score higher than physicians in their assessment of disease activity, particularly for the joint disease.

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The levels of fatigue, pain, and tender joint count were the major determinants of discordance in the assessment of joint activity.

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Lower level of education, unemployment, smoking, depression, anxiety, and fibromyalgia characterized patients who consistently overestimated their disease activity compared to their physicians.

Rheumatology and by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis for the assessment of disease activity in psoriatic disease, including peripheral joint count, skin activity, pain, patient global assessment (PtGA), physical function, and health-related quality of life (2). Additional important domains include enthesitis, dactylitis, fatigue, nail disease, spinal disease, acute-phase reactant, and physician global assessment (PhGA). PtGA was found to be a reliable tool for assessing skin and joint disease activity among patients with PsA (3). However, since the scores of the skin and joint often diverge, it was suggested that each of these domains should be scored separately (4). Studies in rheumatoid arthritis (RA) found discordance between PtGA and PhGA of disease activity in approximately one-third of patients (5–7). However, in PsA there is only limited information about the extent and determinants of patient–physician discordance in perception of disease activity. The emerging paradigm of treat-to-target in patients with PsA highlights the importance of understanding the underlying factors of such patient–physician discordance (8), as all suggested composite scores in PsA encompass patients’ and physicians’ reported outcomes (9). Since treatment decisions are based on such scores, discordance between patient- and physician-based measures may lead to situations where the global score indicates an active disease while the physician perceives the disease as being inactive. Additionally, discordance of disease activity assessment between the physician and the patient is associated with patients’ dissatisfaction, lower adherence to treatment, and poorer disease outcome (10 – 12). Therefore, the aim of this study was to assess the factors contributing to the variability in the scoring of PtGAs and PhGAs and the discrepancy between these scores among PsA patients, as well as to identify characteristics features of patients who consistently rate their disease activity higher than their physician.

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PATIENTS AND METHODS Setting and study population. The study population included adult patients from the University of Toronto PsA cohort. The cohort was established in 1978 as part of an ongoing prospective study. Approximately 98% of the patients in the cohort satisfy the Classification of Psoriatic Arthritis Study Group criteria for classification of PsA (13). The patients are followed in the clinic according to a standard protocol every 6 –12 months (14). Since PtGA and PhGA scores have been collected routinely only since 2009, patients were selected for inclusion in this study only if they have visited the clinic as of January 1, 2009. For the cross-sectional analysis of factors contributing to the variability in scores, the first available visit with complete information was selected. In order to classify patients as those who consistently overestimate their disease activity compared to their physician and as those who tend to be concordant with their physicians’ scoring, all observations available as of January 1, 2009 were used for patients with at least 3 visits in the clinic. All subjects’ written consent was obtained according to the declaration of Helsinki. The study has been approved by the University Health Network Ethics Board. Data collection. All study patients underwent an assessment by a rheumatologist, which included a complete history, physical examination, and laboratory evaluation. Information on demographics, lifestyle habits, comorbid conditions, and disease-related outcome measures for each time point was extracted from the database. Three different outcomes were studied for the skin and the joint domains separately as follows: 1) PhGA of disease activity; for the joint domain the assessing rheumatologist was asked, “how would you rate joint disease in this patient?” (PhGA-joint), and for the skin domain the physician was asked, “How would you rate psoriasis in this patient?” (PhGA-skin), 2) PtGA; for the joint domain the patient was asked, “Considering all the ways your arthritis affects you, rate the way you felt over the past week” (PtGA-joint), and for the skin domain the patient was asked, “Considering all the ways your psoriasis affects you, rate the way you felt over the past week” (PtGA-skin), and 3) difference between PtGA and PhGA; the differences were calculated for the corresponding PtGA and PhGA scores in the skin and the joint domains. The scores of PtGA and PhGA ranged from 0 (best status) to 10 (worst status) on a numeric rating scale (NRS). The difference between PtGA and PhGA reflected the degree of discrepancy between the PtGA and PhGA of joint or skin activity and could take values from 10 (higher rating of disease activity by the patient) to ⫺10 (higher rating of disease activity by the physician). Additional information included age, sex, duration of psoriasis and PsA, ethnicity, a medical diagnosis of depression or anxiety based on patient report, duration of morning stiffness, swollen and tender joint count (66 and 68 joints, respectively), number of dactylitic digits, number of entheseal tender points based on the Spondyloarthritis Research Consortium of Canada enthesitis index,

266 Psoriasis Activity and Severity Index (PASI), the number of fibromyalgia tender points and erythrocyte sedimentation rate. In addition, the study participants completed the following questionnaires estimating their physical functioning and quality of life: Health Assessment Questionnaire (HAQ) disability index, patient’s assessment of pain (on an 11-point NRS), Fatigue Severity Score (FSS) (15), Dermatology Life Quality Index (DLQI) (higher scores reflect a decreased quality of life) (16), and the physical component score (PCS) and the mental component score (MCS) derived from the Short Form 36 (SF-36) health survey. Spinal pain was assessed by using the score for the question, “How would you describe the overall level of neck, back, or hip pain you have had?” taken from the Bath Ankylosing Spondylitis Disease Activity Index. Statistical analysis. The sample distributions of variables were described by their mean ⫾ SD or, for categorical variables, by frequencies and percentages. To identify determinants of PtGA, PhGA, and the difference between them, a descriptive analysis of the correlation between each of these outcomes and disease-related variables was assessed by Pearson’s correlation coefficients. This analysis was done separately for the skin and the joint outcomes. Variables that were found to be significant associated at the 5% level (P less than 0.05) were further assessed in multivariate linear regression models to determine their independent contribution to the variability of each of the investigated outcomes. Stepwise selection with a cut point of P ⬍ 0.15 was used to remove noncontributing variables from the model. The proportion of variability of each outcome explained by each predictor was summarized using the partial R2. An absolute difference between PtGA and PhGA of ⬎2 points on an NRS was considered a clinically relevant discordance. There is no accepted cutoff for relevant patient–physician discordance of disease activity in PsA. In a recent multicenter study that assessed more than 1,500 patients with 5 different rheumatic conditions, including RA and ankylosing spondylitis, a cutoff of 2 points on the NRS was found to be the minimum clinically important improvement for both patient and physician global assessment (17). Since values of approximately 2 were found across 5 rheumatic conditions, we speculate that a similar cut point can be applied for PsA patients. Additionally, most studies that assessed clinically relevant patient– physician discordance of joint activity in the literature used a cutoff of 2 (6,18). Therefore, for consistency with other studies, a difference of ⬎2 points was used to define a clinically relevant discordance. To identify features of patients who consistently rate their disease activity higher or lower than their physician, only individuals who had at least 3 visits with complete data were considered in a secondary analysis. Based on a cutoff of 2 for clinically relevant patient–physician discordance, patients were classified into 1 of the following 3 groups at each visit: 1) patient disease activity higher than the physician (PtGA-PhGA ⬎2), 2) patient disease activity lower than the physician (PtGA-PhGA ⬍2), and 3) scored

Eder et al similar to the physicians (PtGA-PhGA ⫾ 2). Based on these groups, patients were subsequently classified as “overestimators” if they were classified to group 1 in more than 50% of the visits. The remaining patients were classified as “concordants” due to the small number of patients that fell into category 2. The 2 groups were then compared with respect to their demographics, lifestyle habits, and comorbidities at first visit to identify characteristic features of each of these subtypes of patients.

RESULTS A total of 565 patients with complete information about PtGA and PhGA in at least 1 visit were included in the analysis. Sixty-three patients were excluded from the analysis due to incomplete data. These patients were similar to the study population with respect to their age, sex, lifestyle habits, and joint activity; however, they tended to be nonwhite, have a lower level of education, and have more active skin disease. The mean ⫾ SD number of visits per patient was 2.7 ⫾ 1.2. The characteristics of the study population are shown in Table 1. The study population was comprised mostly of patients with longstanding disease and polyarticular involvement, many of whom sustained clinical damage from arthritis. On average, patients tended to score their disease activity higher than their physicians, although the mean ⫾ SD difference was higher for the joints (PtGA-PhGA difference 1.68 ⫾ 2.41; P ⬍ 0.0001) than for the skin (PtGA-PhGA difference 0.77 ⫾ 2.66; P ⬍ 0.0001). Correlation between outcomes and disease-related variables. A moderate correlation was found between PtGA and PhGA of the skin (r ⫽ 0.42, P ⬍ 0.0001) and the joints (r ⫽ 0.54, P ⬍ 0.0001). PtGA-joint explained 29% of the variability in PhGA-joint, and PtGA-skin explained 17.5% of the variability in PhGA-skin. Out of all variables evaluated, tender and swollen joint counts, but also patient pain and function (by SF-36 PCS), were highly correlated with PhGA-joint (Table 2), while PASI and DLQI highly correlated with PhGA-skin. As for PtGA, patient pain, physical functioning (by HAQ and SF-36 PCS), SF-36 MCS, and fatigue highly correlated with PtGA-joint, while only DLQI highly correlated with PtGA-skin. The correlation between patient and physician outcomes and dactylitis, an important clinical manifestation of PsA, was further analyzed in 59 patients who were found to have dactylitis at the time of assessment. A strong correlation between the number of acute (tender) dactylitic digits and PhGA-joint (r ⫽ 0.57, P ⬍ 0.0001) and a weak correlation with PtGA-joint (r ⫽ 0.29, P ⫽ 0.03) was found. On multivariate linear regression analysis, 81% and 72% of the variability in PtGA and PhGA of the joints were explainable, while 57% and 67% of the variability in PtGA and PhGA of the skin were explainable (Figure 1). Factors explaining global assessment of the joints and patient–physician discordance. The results of the multivariate regression analyses showed that the main factors explaining the variability of PtGA-joint were pain on an

Patient–Physician Discrepancy in PsA

Table 1.

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Characteristics of the study population at first assessment (n ⴝ 565)* Characteristic

Value

Age, years Male sex Duration of PsA, years Duration of psoriasis, years White race Current smoker Level of education (⬎12 years) BMI, kg/m2 Swollen joint count Tender joint count Clinically damaged joint count Axial involvement Dactylitis Enthesitis PASI score Psoriatic nail lesions ESR, mm/hour Patient global assessment-joint Mean ⫾ SD Median (IQR) Physician global assessment-joint Mean ⫾ SD Median (IQR) Patient global assessment-skin Mean ⫾ SD Median (IQR) Physician global assessment-skin Mean ⫾ SD Median (IQR) Current use NSAIDs DMARDs Biologic agents

51.7 ⫾ 13.2 331 (58.6) 14.3 ⫾ 19.4 24.0 ⫾ 13.8 490 (87.8) 67 (11.9) 377 (66.7) 29.5 ⫾ 6.5 4.9 ⫾ 6.5 8.5 ⫾ 10.1 12.5 ⫾ 14.1 288 (51.1) 59 (11) 78 (13.8) 3.4 ⫾ 5.3 300 (53.4) 14.3 ⫾ 19.4 3.97 ⫾ 2.67 4 (2–6) 2.29 ⫾ 2.3 2 (0–4) 3.08 ⫾ 2.74 2 (1–5) 2.32 ⫾ 2.10 2 (1–3) 344 (61.4) 304 (54.9) 203 (36.3)

* Values are the mean ⫾ SD or number (percentage) unless indicated otherwise. PsA ⫽ psoriatic arthritis; BMI ⫽ body mass index; PASI ⫽ Psoriasis Area and Severity Index; ESR ⫽ erythrocyte sedimentation rate; IQR ⫽ interquartile range; NSAIDs ⫽ nonsteroidal antiinflammatory drugs; DMARDs ⫽ disease-modifying antirheumatic drugs.

NRS (R2partial ⫽ 72.5%), fatigue (by FSS; R2partial ⫽ 5.5%), and disability scores (by SF-36 PCS and MCS; R2partial ⫽ 2.2%), while the main factors explaining the variability in PhGA-joint were tender joint count (R2partial ⫽ 54%), swollen joint count (R2partial ⫽ 4%), and patient pain (R2partial ⫽ 6.8%). Interestingly, dactylitis, enthesitis, and the severity of back pain did not significantly affect the variability in physician assessment after adjusting for other variables. The difference between PtGA and PhGA was predominantly explained by fatigue, tender joint count, and pain. Increased fatigue accounted for 21.3% of the variation in the difference between PtGA and PhGA, and pain (R2partial ⫽ 9.2%) was also important; these led to worse patient assessments. Increased tender joint (R2partial ⫽ 16.3%) and swollen joint (R2partial ⫽ 1.5%) counts resulted in a worse physician assessment of arthritis (Table 3). This association is also illustrated in Figure 2, which shows the correlation between tender joint count and fatigue as predictors of the level of discordance in global

assessment of joint activity. A low prevalence of discordant patients was observed at the lower levels of fatigue, while the frequency of discordant patients rose markedly at the high levels of fatigue. An opposite trend was observed for tender joint count. Among patients with lower tender joint count there was a high prevalence of discordant patients, while this dropped significantly for patients with high tender joint counts. Factors explaining global assessment of the skin and patient–physician discordance. The predominant factor explaining the variability of PtGA-skin was DLQI (R2partial ⫽ 45.7%). Interestingly, patient pain explained 9.7% of the variability of PtGA-skin, while PASI did not have an independent effect. As expected, PASI was the factor explaining most of the variability in PhGA-skin (R2partial ⫽ 62.2%), and DLQI and swollen joint count had a small effect (R2partial of 3.2% and 1.3%, respectively). The discordance between PtGA and PhGA of the skin was primarily explained by pain, DLQI, and PASI. Increased pain accounted for 17.3% of the variation in the difference between PtGA and PhGA of the skin, and DLQI (R2partial ⫽ 14%) was also important; these led to worse patient assessments. Increased PASI (R2partial ⫽ 11.8%) resulted in a worse physician assessment of psoriasis (Table 3). Proportion of discordance. Out of the 565 study subjects, the 311 who had 3 or more visits in the clinic (mean ⫾ SD 3.6 ⫾ 0.7 visits) were analyzed for clinically meaningful discordance. The 254 patients with fewer visits, who were excluded from this analysis, tended to be nonwhite, have shorter disease duration, and higher levels of pain. No difference was found with respect to the remaining demographic and clinical variables between the 2 groups. Among the 311 patients who had ⱖ3 visits in the clinic, a patient–physician difference of ⬎2 points on an NRS (patient scores worse than physician, or “overestimators”) was consistently found in 97 of patients (31.2%) for the joints and 48 of patients (15.4%) for the skin. Only 5 (1.6%) patients consistently scored lower than the physician in their assessment of the joints, and 21 (6.8%) patients scored lower for the skin assessment (patient score less severe than the physician). The remaining 67.2% and 77.8% of patients consistently scored similarly (“concordant”) to the physicians with respect to their skin and joint global assessment. Characteristics of consistently discordant patients. We assessed the characteristics of patients who consistently scored higher than their physicians (“over-estimators”) by comparing them to the concordant group. The results are presented in Table 4. Patients who consistently overestimated their skin and joint disease activity tended to have a lower education level, be smokers, be unemployed, and experience depression, anxiety, and fibromyalgia. In addition, older age, female sex, and higher damage joint count were associated with consistent overestimation of joint activity, while living without a partner was associated with consistent overestimation of the skin.

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Table 2. The correlation between disease-related variables and disease activity (PtGA, PhGA, and patient–physician discordance) by Pearson’s correlation coefficient* Joint activity

Skin activity

Variable

PtGA

PhGA

PtGA-PhGA difference

Duration of PsA Tender joint count Swollen joint count No. dactylitic digits Active entheseal sites Damaged joint count Duration of morning stiffness PASI score CRP, mg/dl ESR, mm/hour Fibromyalgia tender points HAQ score DLQI score Back pain Patient global pain Fatigue score SF-36 MCS SF-36 PCS

⫺0.10† 0.42‡ 0.30‡ 0.18‡ 0.22‡ ⫺0.07 0.29‡

⫺0.21‡ 0.73§ 0.65§ 0.35‡ 0.37‡ ⫺0.16‡ 0.28‡

0.09† ⫺0.23‡ ⫺0.29‡ ⫺0.14‡ ⫺0.11‡ 0.07 0.06

⫺0.14‡ ⫺0.06 0.28‡ 0.25‡ 0.22‡ 0.25‡ 0.16‡ 0.15‡ 0.16‡ 0.14‡ ⫺0.04 0.03 0.19‡ 0.04

⫺0.10† 0.13‡ 0.03 0.04 0.06 ⫺0.07 0.17‡

0.08 0.21‡ 0.13‡ 0.31‡ 0.68‡ 0.34‡ 0.69‡ 0.84§ 0.70§ ⫺0.56§ ⫺0.77§

0.12‡ 0.27‡ 0.18‡ 0.15‡ 0.47‡ 0.24‡ 0.44‡ 0.56§ 0.36‡ ⫺0.26‡ ⫺0.50§

⫺0.03 ⫺0.02 ⫺0.03 0.19‡ 0.31‡ 0.14‡ 0.35‡ 0.40‡ 0.44‡ ⫺0.37‡ ⫺0.38‡

0.29‡ 0.79§ 0.17‡ 0.19‡ 0.12‡ 0.18‡ 0.18‡ ⫺0.01 0.35‡ 0.08 0.68§ 0.51§ 0.43‡ 0.09† 0.49‡ 0.13‡ 0.42‡ 0.07 ⫺0.41‡ ⫺0.05 ⫺0.41‡ ⫺0.10†

⫺0.33‡ 0.02 ⫺0.03 0.20‡ 0.30‡ 0.30‡ 0.36‡ 0.40‡ 0.37‡ ⫺0.38‡ ⫺0.34‡

PtGA

PhGA

PtGA-PhGA difference

* PtGA ⫽ patient global assessment; PhGA ⫽ physician global assessment; PsA ⫽ psoriatic arthritis; PASI ⫽ Psoriasis Area and Severity Index; CRP ⫽ C-reactive protein; ESR ⫽ erythrocyte sedimentation rate; HAQ ⫽ Health Assessment Questionnaire; DLQI ⫽ Dermatology Life Quality Index; SF-36 ⫽ Short Form 36 health survey; MCS ⫽ mental component score; PCS ⫽ physical component score. † P ⬍ 0.05. ‡ P ⬍ 0.01. § P ⬍ 0.01; variable with high correlation (r ⬎ 0.5).

DISCUSSION In this study we assessed the extent and determinants of discordance between PtGA and PhGA of disease activity in 2 primary domains of PsA: psoriasis and arthritis. In accordance with previous reports, we found that patients tended to score higher than physicians in their assessment. The level of patient–physician discordance was higher for the joint disease. The severity of fatigue, pain, and tender joint count were the major determinants of discordance in the assessment of joint activity. Lower level of education, unemployment, smoking, and the presence of depression, anxiety, and fibromyalgia characterized patients who consistently overestimated their disease activity. The discrepancy between PtGA and PhGA of disease activity has been thoroughly investigated in RA patients; however, only a single small study addressed the issue in PsA patients (6,18 –22). In line with our results, these studies showed that patients, on average, rated their disease activity higher than did the physicians. At a cutoff of ⬎2 cm on a 10-cm visual analog scale, approximately one-third of RA patients were found to have a clinically relevant discordance, estimates that are similar to the proportion of discordant patients in our study (6,18). We found that high levels of pain and fatigue are the most important factors explaining the variability in discrepancy between patients’ and physicians’ assessments of the joints. In contrast to studies in RA, swollen joint count was not an important determinant of that discordance, explain-

ing only 4% of the variability. The reason for that finding is unclear. In RA, high level of pain, poor function, and fewer swollen joints were associated with higher rating of disease activity by the patients compared to the physicians (6,18,20). However, it should be noted that fatigue was not assessed as a predictor in several of these studies. Dandorfer et al reported that among PsA patients discordance was found primarily in women, patients age ⬎50 years, and in those with early disease (19). These data highlight the importance of incorporating both patient and physician assessments in composite outcome scores in PsA, as these scores represent different constructs. Pain is the major complaint of our patients, as it underscores 72.5% of the PtGA of the joint. Although it is also an indirect determinant of the PhGA through the tender joint count, the subjective nature of this complaint leads to different perceptions of disease activity by patients and physicians. The assessment of the source of pain may be more complicated in PsA patients compared to RA, as the former may affect the spine, tendons, and enthesis in addition to the peripheral joints. Other extraarticular sites may also be the source of pain in PsA, including the soft tissue, skin, and nails. In our study, patient pain was the second most important predictor of PtGA of the skin activity, and was the predominant factor explaining the variability in patient–physician discordance of the skin activity. Chronic pain disorders, such as fibromyalgia, may be another source of pain. Although patients with PsA tend to

Patient–Physician Discrepancy in PsA

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Figure 1. Factors affecting the variability in patient global assessment (PtGA) and physician global assessment (PhGA) (% of adjusted R2) of the joints and skin. EMS ⫽ duration of morning stiffness; SF-36 ⫽ Short Form 36 health survey; TJC ⫽ tender joint count; SJC ⫽ swollen joint count; HAQ ⫽ Health Assessment Questionnaire; PASI ⫽ Psoriasis Area and Severity Index; DLQI ⫽ Dermatology Life Quality Index; MCS ⫽ mental component summary.

taken to investigate occult musculoskeletal inflammation, such as enthesitis or spondylitis, using sensitive imaging studies. The identification of such inflammation may require augmentation of antiinflammatory treatments. Skin and nail disease should also be considered as well when

be less “tender” than RA patients (23), the prevalence of fibromyalgia symptoms in PsA patients can range from 6.9 –53.3% (24,25). Identifying the source of pain is of major importance as it may affect the diagnostic examination and treatment decisions. Any effort should be underTable 3.

Variables associated with patient–physician discordance in disease activity by linear regression analysis*

Discrepancy in PtGA and PhGA-joint Fatigue severity score Tender joint count Patient pain Swollen joint count Fibromyalgia tender points Clinically damaged joints SF-36 MCS SF-36 PCS Discrepancy in PtGA and PhGA-skin Patient pain PASI score DLQI score SF-36 MCS

␤

95% CI

P

Partial R2, %

0.19 ⫺0.12 0.27 ⫺0.09 0.05 0.01 ⫺0.03 ⫺0.03

0.10, 0.28 ⫺0.15, ⫺0.09 0.17, 0.37 ⫺0.14, ⫺0.04 0.01, 0.09 0.001, 0.027 ⫺0.047, ⫺0.009 ⫺0.055, ⫺0.004

⬍ 0.0001 ⬍ 0.0001 ⬍ 0.0001 0.0003 0.02 0.02 0.02 0.02

21 16 9 1.4 0.6 0.6 0.6 0.6

0.27 ⫺0.26 0.22 ⫺0.02

0.17, 0.36 ⫺0.29, ⫺0.22 0.17, 0.26 ⫺0.04, ⫺0.004

⬍ 0.0001 ⬍ 0.0001 ⬍ 0.0001 0.001

17.4 11.7 14 1.3

* 95% CI ⫽ 95% confidence interval; PtGA ⫽ patient global assessment; PhGA ⫽ physician global assessment; SF-36 ⫽ Short Form 36 health survey; MCS ⫽ mental component score; PCS ⫽ physical component score; PASI ⫽ Psoriasis Area and Severity Index; DLQI ⫽ Dermatology Life Quality Index.

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Figure 2. Scatter plots showing the discordance between patient global assessment (PtGA) and physician global assessment (PhGA) of the joint activity as a function of fatigue and measured by the Fatigue Severity Scale (FSS) (A) and tender joint count (B). Horizontal lines denote clinically relevant discordance (⬎2 points difference in PtGA-PhGA).

considering new medications. Finally, when central sensitization of pain is thought to play a role, different therapeutic measures may be required as peripheral inflammation may no longer be present. Fatigue is considered an important core domain in clinical trials and observational studies in PsA. It was another important source of discordance between PtGA and PhGA. As in many other chronic conditions, fatigue is an important complaint in PsA patients, affecting all aspects of life. Husted et al reported that 49.5% of the patients in our cohort experienced moderate fatigue, while 28.7% had severe fatigue (15). Fatigue was associated with pain, poor physical function, and psychological stress, and was more frequently reported by women. Despite the frequent cooccurrence of pain and fatigue, the latter is not a redundant measure, as in our study it explained a significant proportion of the variability in discordance of the joint assessment after controlling for pain. Furthermore, the Table 4.

frequency of discordant patients increased with rising level of fatigue. Fatigue is multifactorial and may be attributed to active systemic inflammation, comorbid conditions, medications such as methotrexate, or poor sleep quality. Physicians may neglect the assessment of fatigue and focus on alternative outcomes that are easier to measure and quantify. Data from clinical trials suggest that blockage of tumor necrosis factor ␣ can improve symptoms of fatigue in patients with PsA. However, it is unclear whether this effect is related to improved control of the systemic inflammation or related to central nervous system mechanisms involved in sleep control (26). Additional studies are required to address this issue in patients with PsA. Although pain and fatigue are the 2 major causes explaining the discrepancy between PtGA and PhGA, another potential explanation might be that, although the questions for the patients are asking about the joints and

Characteristics of consistent overestimators of disease activity vs. concordant patients* Joint assessment

Skin assessment

Variable

Overestimators (n ⴝ 97)

Concordants† (n ⴝ 214)

P

Overestimators (n ⴝ 48)

Concordants† (n ⴝ 263)

P

Age, years Female sex White race Education level ⬎12 years Marital status live alone Unemployed Smoking ever Duration of PsA BMI Anxiety/depression Fibromyalgia Damaged joint count

55.8 ⫾ 11.3 50 (51.6) 88 (90.7) 66 (68) 30 (31.2) 53 (55.2) 61 (62.9) 17.5 ⫾ 12.1 31.1 ⫾ 5.5 34 (35.1) 21 (21.7) 16.7 ⫾ 16.7

50.8 ⫾ 12.6 74 (34.6) 195 (91.1) 172 (80.4) 59 (27.6) 63 (29.4) 93 (43.5) 14.4 ⫾ 11 28.2 ⫾ 5.6 28 (13.1) 12 (5.6) 10.4 ⫾ 11.6

0.001 0.005 0.91 0.02 0.51 ⬍ 0.001 0.002 0.02 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001 0.009

53 ⫾ 13.4 24 (50) 42 (87.5) 31 (64.6) 20 (41.7) 15 (31.9) 30 (62.5) 14.6 ⫾ 12.9 29.8 ⫾ 4.9 23 (47.9) 16 (33.3) 12 ⫾ 14.2

52.3 ⫾ 12.3 100 (38) 241 (91.6) 207 (78.7) 69 (26.3) 179 (68.1) 124 (47.2) 15.5 ⫾ 11.2 29 ⫾ 5.9 39 (14.8) 17 (6.5) 12.4 ⫾ 13.6

0.73 0.12 0.36 0.03 0.03 ⬍ 0.001 0.05 0.61 0.40 ⬍ 0.001 ⬍ 0.001 0.89

* Values are the mean ⫾ SD or number (percentage) unless indicated otherwise. PsA ⫽ psoriatic arthritis; BMI ⫽ body mass index. † Concordant group included are also underestimators of disease activity.

Patient–Physician Discrepancy in PsA the psoriasis, the patients are rating their general feelings in both questions. This may be supported by the strong correlation between PtGA-skin and PtGA-joint (r ⫽ 0.57), as opposed to the weak correlation between PhGA-joint and PhGA-skin (r ⫽ 0.23). This study had several limitations. The characteristics of the assessing rheumatologists were not considered as potential determinants of the outcome. Although age, sex, and level of experience of the physician may affect their perception of disease activity, to simplify matters we focused on patient characteristics as the primary predictor of the outcome. Physician characteristics may explain part of the unexplainable variability of the PhGA. Secondly, the assessment of depression and anxiety was based on patient report and use of antidepressant medications and may underestimate the effect of psychiatric symptoms on the outcome. We did consider the MCS of the SF-36 as a surrogate for psychological distress. This measure did not contribute significantly to the variability of discordance. The strengths of the study include its large size, accurate phenotyping of the patients, and the use of longitudinal data to explore the determinants of discordance between patients and physicians. In conclusion, we have found a significant proportion of discordance between patient and physician assessment of the joint disease in patients with PsA. Higher levels of agreement were observed for skin disease. We suggest that these measures be assessed separately in patients with PsA. Pain and fatigue are the 2 major determinants of discordance between patient and physician assessment. Efforts to investigate the underlying causes of these symptoms and the adjustment of treatment accordingly may improve the control of disease-related symptoms. Future studies should focus on the underlying mechanisms related to the perception of pain and fatigue in PsA patients and on methods to identify noninflammatory pain in these patients. 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. Gladman 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. Eder, Thavaneswaran, Chandran, Cook, Gladman. Acquisition of data. Eder, Chandran, Gladman. Analysis and interpretation of data. Eder, Thavaneswaran, Chandran, Cook, Gladman.

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