Journal of Dermatological Treatment.

2006; 17: 279287

ORIGINAL ARTICLE

Clinical characteristics of psoriatic arthritis and psoriasis in dermatologists offices

ALICE B. GOTTLIEB1, PHILIP J. MEASE2, J. MARK JACKSON3, DRORE EISEN4, H. AMY XIA5, CHARLES ASARE5 & SETH R. STEVENS5
Department of Dermatology, TuftsNew England Medical Center, Boston, MA, USA, 2Seattle Rheumatology Associates, Seattle, WA, USA, 3Dermatology Specialists, Louisville, KY, USA, 4Dermatology Research Associates, Cincinnati, OH, USA, and 5Amgen Inc., Thousand Oaks, CA, USA
1

Abstract Objective: To describe the skin and joint disease of patients with psoriatic arthritis being treated in dermatology clinics. Methods: A total of 1122 patients who had active psoriatic arthritis were enrolled in a Phase 4, non-randomized, open-label, single-arm, 24-week study. They were treated at 108 community and 17 academic dermatology centers. These patients experienced clinically stable, plaque psoriasis involving >10% body surface area and joint disease (either > two swollen and > two tender/painful joints for >3 months, or > one joint with sacroiliitis or spondylitis). Results: In general, patient demographics and disease characteristics did not appear to differ between academic and community dermatology sites. Based on patient-reported assessments, patients rated the severity of their baseline joint symptoms lower than the severity of their skin disease. Baseline skin and joint disease measures were not correlated. Psoriatic arthritis was newly diagnosed in 23% of the patients. Most had received prior therapy for psoriasis, but only half had received systemic therapy for psoriatic arthritis. Conclusion: Assessment for joint disease in psoriasis patients being treated at dermatology clinics may facilitate earlier psoriatic arthritis diagnosis and treatment initiation, which may prevent disability and other negative impacts.

Key words: Clinical trial, EDUCATE, Phase 4, psoriasis, psoriatic arthritis

Introduction Psoriatic arthritis is a chronic and progressive form of inflammatory arthritis (1,2) that frequently leads to significant physical limitations and reduced quality of life (35). Estimates of the prevalence of psoriatic arthritis in patients with psoriasis vary widely, and range from 6% to 39% (69). The combination of skin and joint disease in the ,80% of psoriatic arthritis patients with psoriasis leads to unique disabilities and emotional problems (3,4), resulting in restrictions in social activities and reductions in work productivity (10). Patients with both psoriatic arthritis and psoriasis therefore experience substantial benefits from treatment for both diseases. Since skin signs and symptoms precede arthritic signs and symptoms in 80% of psoriatic arthritis patients (11), patients may present first with skin disease at dermatology clinics and are subsequently

referred to rheumatologists as joint symptoms become problematic. The course of joint disease in these patients can be significant: with respect to the progression of joint erosion alone, one report indicated that, despite exhibiting clinical improvement, 47% of psoriatic arthritis patients exhibited erosions after a median of 2 years while only 27% had erosions at baseline (1). In another report, it was observed that nearly a quarter of patients demonstrate joint erosions 1 year after diagnosis (12). Recent studies suggest that the pathophysiology of both psoriatic arthritis (13) and psoriasis (14) is mediated by pro-inflammatory cytokines, most notably tumor necrosis factor (TNF). Elevated levels of TNF have been found in psoriatic skin lesions (15) and synovial fluid in patients with psoriatic arthritis (16). In a recent review, Mease provides a broader discussion of a role for TNFa therapy in psoriatic arthritis and psoriasis (17). Traditional immunosuppressive therapies used in the treatment

Correspondence: Alice B. Gottlieb, TuftsNew England Medical Center, 750 Washington St., Box 114, Boston, MA 02111-1533, USA. Fax: 1 617 636 9169. E-mail: agottlieb@tufts-nemc.org (Received 22 May 2006; accepted 23 May 2006) ISSN 0954-6634 print/ISSN 1471-1753 online # 2006 Taylor & Francis DOI: 10.1080/09546630600823369

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A. B. Gottlieb et al. Study design The EDUCATE study is a Phase 4, multicenter, open-label, clinical trial designed to investigate the effect of etanercept treatment in treating the signs and symptoms associated with joint and skin manifestations in patients with psoriatic arthritis in dermatology clinics. The institutional review boards of the participating sites approved the study protocol, and all patients provided written informed consent before any study-related procedures were performed. This report describes the baseline patient demographic characteristics and baseline joint and skin disease observed in these patients. First, patient-reported assessments were collected using a subject assessment booklet containing the following: patient global assessments of joint disease, joint pain, and psoriasis, a pharmacoeconomic questionnaire, patient assessment of morning stiffness duration, Health Assessment Questionnaire disability index (HAQ-DI), and Dermatology Life Quality Index (DLQI). Dermatologists performed the physician global assessment of psoriasis and the assessments of joint disease. Assessment of psoriasis included a physician global assessment of psoriasis (21), BSA involvement, history (duration) of skin disease, and treatments. The physician global assessment of psoriasis measures psoriasis severity with respect to erythema, scaliness, and induration, and is independent of the extent of skin disease. Patient-reported skin assessments at baseline consisted of Patient Global Assessment of Psoriasis, itching intensity, and DLQI (22,23). Joint disease parameters assessed included swollen and tender/painful joint counts (24), presence of spondylitis, history (duration) of joint disease, and prior treatments. Psoriatic arthritis subtypes also were evaluated, and physicians were allowed to document multiple subtypes, if present, and not just the predominant subtype. Patients provided a patient global assessment of joint disease, patient global assessment of joint pain, patient assessment of the duration of morning stiffness, and HAQ-DI score (2426). The patient global assessment of joint disease instrument is a patient-reported outcome assessment that asks, How active do you feel your joint disease is today? Patients are requested to score their joint disease on a range of 05, with 5 being the most severe joint disease. Similarly, the patient global assessment of joint pain instrument asks, How active do you feel your joint pain is today? This assessment is scored on a range of 010, with 10 being the most severe joint pain. The HAQDI score was used to measure functional ability by asking questions about movements of the upper and lower extremities, both in terms of independent activities and activities that include both (25). HAQDI scores range from 0 to 3, with 0 indicating patients are able to perform the activities of daily

of psoriasis have been largely ineffective at preventing progression of joint disease in patients with psoriatic arthritis (11). Therapies targeting TNF, however, have been shown to relieve symptoms of both diseases in recent clinical trials (18,19). Etanercept is a soluble TNF receptor-IgG1 fusion protein that binds to both soluble and membranebound TNF, thereby inhibiting its interaction with cell surface receptors and preventing TNF-mediated cellular responses. Etanercept has been approved by the FDA and by the European Commission (EC) for the treatment of patients with psoriatic arthritis, psoriasis, rheumatoid arthritis, polyarticular juvenile rheumatoid arthritis, and ankylosing spondylitis (20). A review of the literature suggests that few clinical trials of treatments for psoriatic arthritis have been conducted in patients being treated at dermatology clinics. Further, little is known about the progression of psoriatic arthritis in patients being treated in this setting. Increased awareness of the incidence, signs, symptoms, and differential diagnosis of psoriatic arthritis in patients with psoriasis among dermatologists may lead to its earlier diagnosis and initiation of therapy, therefore preventing disability and progression of the disease. This report describes the demographic and baseline characteristics of patients enrolled in a large Phase 4, open-label, primarily community-based clinical trial, named Experience Diagnosing, Understanding Care, and Treatment with Etanercept (EDUCATE), of patients with psoriatic arthritis being treated in dermatology clinics in the USA. The purpose is to provide dermatologists with a glimpse of the nature of the psoriatic arthritis patient being treated in the dermatology clinic.

Methods Patients Patients with both arthritic and psoriatic symptoms were recruited from 108 community- and 17 academia-based dermatology clinics. Key eligibility criteria were: age >18 years; active psoriatic arthritis defined by > two swollen joints and > two tender/ painful joints, or the presence of sacroiliitis or spondylitis in > one joint; and clinically stable plaque psoriasis involving >10% body surface area (BSA). Patients were ineligible for enrollment if they had: active rheumatoid arthritis or osteoarthritis; skin conditions other than plaque psoriasis; use of oral retinoids or psoralen-ultraviolet A (PUVA) therapy within 28 days of baseline visit; use of vitamin A or D analog preparations, anthralin or ultraviolet B (UVB) therapy within 12 days of baseline; evidence of active infection; or severe comorbidities. Patients gave informed consent before participating in this study.

EDUCATE baseline profile living without difficulty and 3 indicating patients are unable to perform these activities. For further information on assessments, see the review of psoriatic arthritis assessments by Gladman et al. (27). Statistical methods Patient demographic and disease characteristics were summarized descriptively by type of site (academic versus community) and by all patients enrolled. Correlations between quality of life measures for skin disease (DLQI) and joint disease and patient assessments for both conditions were performed using Spearman rank correlations. Linear regression analyses were used to examine the relationships between baseline quality of life measures and patient assessments of disease.

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enrolled at academic dermatology clinics. Baseline patient and disease characteristics are described for each site type and for all patients combined (Tables I, II, and III). In general, patient and disease characteristics were similar between academic and community dermatology sites; therefore, characteristics are described for all patients combined, unless differences were noted. Demographics The mean age was 48 years, and the patient population was predominantly white (85%) with a slight preponderance of males (55%) (Table I). Employment status Most patients (60%) were employed full time at the start of the trial (Table I). Few patients were disabled (4%) or temporarily disabled (0.4%). Skin disease The mean duration of psoriasis was 19 years, and mean BSA involvement was 27%. Physician global assessment of psoriasis indicated that the severity of psoriasis was moderate to severe in 80% of patients (Table II), which was consistent with patient-

Results Patients A total of 1122 patients with both psoriatic arthritis and psoriasis being treated in community-based and academic dermatology clinics were assessed. Of these, 931 patients were enrolled at communitybased dermatology clinics and 191 patients were

Table I. Patient characteristics. PsA patients by site type Academic sites (n5191) Age, mean, years (SD) Age, range, years Sex, n, males (%) Race, n, white (%) Height, mean, cm (SD) Height, range, cm Weight, mean, kg (SD) Weight, range, kg Highest level of education, n (%) Grades K8 Grades 912 or GED Technical school Some college College Postgraduate Employment status, n (%) Full-time (w35 hours per week) Part-time (v35 hours per week) Temporarily disabled Disabled Retired Unemployed Other 48.3 1977 105 155 170.6 142196 90.7 46.8158.5 5 36 10 48 58 34 115 21 2 10 24 14 5 (12.5) (55.0) (81.2) (11.3) (23.1) Community sites (n5931) 47.9 1888 507 793 170.9 127206 89.6 43.7198.0 23 304 39 230 233 102 561 82 3 37 144 85 19 (13.6) (54.5) (85.2) (11.2) (22.0) All sites (n51122) 48.0 1888 612 948 170.8 127206 89.8 43.7198.0 28 340 49 278 291 136 676 103 5 47 168 99 24 (13.4) (54.5) (84.5) (11.2) (22.1)

(2.6) (18.8) (5.2) (25.1) (30.4) (17.8) (60.2) (11.0) (1.0) (5.2) (12.6) (7.3) (2.6)

(2.5) (32.7) (4.2) (24.7) (25.0) (11.0) (60.3) (8.8) (0.3) (4.0) (15.5) (9.1) (2.0)

(2.5) (30.3) (4.4) (24.8) (25.9) (12.1) (60.2) (9.2) (0.4) (4.2) (15.0) (8.8) (2.1)

PsA5psoriatic arthritis; n5number of patients in intent-to-treat analysis; SD5standard deviation; range5minimum to maximum; GED5general equivalency diploma.

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Table II. Patient disease characteristics. PsA patients by site type Academic sites (n5191) Skin disease characteristics Duration of psoriasis, mean, years (SD) 20.9 BSA affected by psoriasis, mean, % (SD) 24.0 BSA affected by psoriasis, range, % 10.090.0 Physician global assessment of psoriasis, n (%) Almost clear 3 Mild 29 Moderate 98 Marked 50 Severe 11 Joint disease characteristics Duration of PsA, mean, years (SD) 7.7 (8.9) PsA subtypea, n (%) Asymmetric polyarthritis or 128 oligoarthritis Symmetric polyarthritis 49 Spondyloarthritis 53 Distal interphalangeal joint disease 61 Arthritis mutilans 4 Tender/painful joint count, n, mean (SD) 14.1 Tender/painful joint count, range 071 Swollen joint count, n (SD) 8.4 Swollen joint count, range 058 Spondylitis present, n (%) 50 Community sites (n5931) All sites (n51122)

(13.5) (17.3)

18.6 27.4 10.091.0 25 171 512 191 32 7.1 (8.2)

(12.70) (19.8)

19.0 26.8 10.091.0 28 200 610 241 43 7.2 (8.3)

(12.9) (19.4)

(1.6) (15.2) (51.3) (26.2) (5.8)

(2.7) (18.4) (55.0) (20.5) (3.4)

(2.5) (17.8) (54.4) (21.5) (3.8)

(67.0) (25.7) (27.7) (31.9) (2.1) (17.2) (10.8) (26.2)

471 462 285 398 23 9.0 060 5.0 060 291

(50.6) (49.6) (30.6) (42.7) (2.5) (8.7) (6.0) (31.3)

599 511 338 459 27 9.9 071 5.6 060 341

(53.4) (45.5) (30.1) (40.9) (2.4) (10.8) (7.2) (30.4)

PsA5psoriatic arthritis; n5number of patients in intent-to-treat analysis; SD5standard deviation; BSA5body surface area; range5minimum to maximum. aPercentages add up to more than 100% because some patients were diagnosed with more than one PsA subtype in different joints.

reported global assessment of psoriasis (mean score 4.0 on a scale of 05) (Table III). Patients also reported a mean score of 14 (on a scale of 030) on

the DLQI, suggesting that skin disease had a profound negative influence on quality of life in these patients.

Table III. Patient-reported assessment of disease. PsA patients by site type Academic sites (n5191) Skin disease assessment Global Assessment of Psoriasis, mean score (SD) Global Assessment of Psoriasis, range Itching, mean score (SD) DLQI, mean score (SD) Joint disease assessment Global Assessment of Joint Disease, mean score (SD) Global Assessment of Joint Pain, mean score (SD) Duration of morning stiffness, median, min/day (range) HAQ Disability Domain, mean score (SD) Community sites (n5931) All sites (n51122)

4.1 15 3.8 14.3 3.0 4.9 90.0 0.85

(0.9)

3.9 15

(1.0)

4.0 15

(1.0)

(1.2) (7.0) (1.0) (2.2) (0720) (0.6)

3.6 13.9 2.8 4.5 90.0 0.78

(1.3) (6.9) (1.1) (2.3) (0720) (0.6)

3.6 13.9 2.8 4.6 90.0 0.79

(1.3) (6.9) (1.1) (2.3) (0720) (0.6)

PsA5psoriatic arthritis; n5number of patients in intent-to-treat analysis; SD5standard deviation; DLQI5Dermatology Life Quality Index; range5minimum to maximum; HAQ5Health Assessment Questionnaire.

EDUCATE baseline profile Joint disease At baseline, the mean tender/painful joint count (510), mean swollen joint count (5six), and median duration of morning stiffness (90 minutes per day) were indicative of significant joint disease. All of the major subtypes of psoriatic arthritis were represented in the patient population, with some patients presenting at study baseline with more than one subtype, the reason why the subtype percentages in Table II add up to more than 100%. The most crippling subtype, arthritis mutilans, was uncommon (2.4% of patients) (Table II). In contrast to patient ratings of skin disease, the mean score of the patientreported global assessment of joint disease was 2.8 on a scale of 05, suggesting that the patients rated the severity of their joint symptoms lower than the severity of their skin disease (Table III). The mean score on the HAQ-DI score was 0.79 on a scale of 0 (no difficulty) to 3 (unable to do), suggesting some degree of disability. There were slight differences in the distribution of psoriatic arthritis subtypes between type of site and in the mean number of tender/painful and swollen joints (Table II). Psoriatic arthritis was newly diagnosed in 258 patients (23%), defined as less than 1 year since diagnosis to study entry. These newly diagnosed patients had a mean of 9.0 tender/painful joints, a mean of 4.7 swollen joints, and a mean HAQ-DI score of 0.71. Relationship of skin and joint disease The mean duration of psoriasis (19 years) was longer than the mean duration of psoriatic arthritis (7 years) (Table II). This finding is consistent with the pattern of disease onset, with the majority of patients (84%) experiencing skin symptoms prior to the onset of joint symptoms (Table IV). Simultaneous onset of arthritic and psoriatic symptoms occurred in only 13% of patients. Only 3% of patients had joint involvement preceding skin involvement. Based on linear regression analyses, health-related quality of life measures for skin disease, as assessed by DLQI, correlated with patient assessments of skin disease (Spearman rank correlation r50.47; pv0.0001). Similarly, HAQ-DI measurements correlated with patient assessments of joint disease

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(r50.48; pv0.0001). These correlations were disease-specific; however, there was no correlation between patient assessments of joint disease and DLQI (r50.20; p50.29), or between patient assessments of skin disease and HAQ (r520.03; p50.14) according to linear regression analyses. Thus, in our cohort of patients, the DLQI and HAQ-DI scores appeared to specifically measure the impact of skin and joint disease, respectively. Therapy Prior medication history was collected; specific therapies were categorized as to possible use for treatment of psoriasis or psoriatic arthritis. Many patients had received two or more systemic therapies that could be used for psoriasis (Table V) or psoriatic arthritis (Table VI). Methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) were the most common systemic therapies, being administered in 38% and 28% of patients, respectively (Table VII). However, 42% and 50% of patients had received no prior systemic therapy for psoriasis or psoriatic arthritis, respectively. Half of the patients (50%) had undergone prior phototherapy, with 11% having received both PUVA and UVB (Tables V and VII). More than 80% of patients (84%) had a history of previous topical therapy use; the most common were topical corticosteroids (56%) and vitamin D analogs (52%). These data demonstrate that, despite meaningfully active joint disease, many patients received no therapy to address this important aspect of the disease. Discussion This report describes the demographics and disease characteristics of over 1100 patients with psoriatic arthritis being treated in dermatology clinics who were enrolled in a clinical trial. Most patients were being treated at community dermatologist offices (n5931), rather than at academic dermatologist offices (n5191). One of the key observations at baseline is that nearly a quarter of patients who enrolled in this trial were diagnosed with psoriatic arthritis within 1 year before the screening visit. This

Table IV. Pattern of disease onset. PsA patients by site type Academic sites (n5191) Skin then joint (%) Joint then skin (%) Simultaneous (%) PsA5psoriatic arthritis. 165 2 24 (86.4) (1.0) (12.6) Community sites (n5931) 777 33 119 (83.5) (3.5) (12.8) 942 35 143 All sites (n51122) (84.0) (3.1) (12.7)

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Table VII. Select therapies by type used for psoriasis or psoriatic arthritis before enrollment in the study. PsA patients (n51122) PsA patients (n51122) Systemic therapies, n (%) Methotrexate NSAIDs Corticosteroids Oral retinoids Cyclosporine Sulfasalazine Hydroxychloroquine Topical therapies n (%) Topical corticosteroids Vitamin D analogs Tar compounds Vitamin A analogs Phototherapies, n (%) PUVA UVB

Table V. Prior treatments for psoriasis.

Systemic therapies, n (%) Number of patients with >1 prior psoriasis systemic therapy Number of prior psoriasis systemic therapies used: no therapy 1 therapy 2 therapies 3 therapies 4 therapies 5 therapies Phototherapies n (%) Number of patients with >1 prior phototherapy Number of prior phototherapies used: no therapy 1 therapy 2 therapies Topical therapies, n (%) Number of patients with >1 prior topical therapy Number of prior topical therapies used: no therapy 1 therapy 2 therapies 3 therapies 4 therapies >5 therapies

652

(58.1)

470 363 214 62 11 2 565 557 439 126 941 181 277 265 203 110 86

(41.9) (32.4) (19.1) (5.5) (1.0) (0.2) (50.4) (49.6) (39.1) (11.2) (83.9) (16.1) (24.7) (23.6) (18.1) (9.8) (7.7)

431 319 215 132 103 32 12 632 587 396 143 254 436

(38.4) (28.4) (19.2) (11.8) (9.2) (2.9) (1.1) (56.3) (52.3) (35.3) (12.7) (22.6) (38.9)

PsA5psoriatic arthritis; n5number of patients in the intent-totreat analysis; NSAIDs5non-steroidal anti-inflammatory drugs; PUVA 5 psoralen plus ultraviolet A radiation therapy; UVB5ultraviolet B radiation.

n5Number of patients in intent-to-treat analysis; PsA5psoriatic arthritis.

observation suggests a possible under-recognition or undertreatment of psoriatic arthritis, which has been described by others (28). One possibility is that the joint disease in these patients may be being masked by the severity of the skin disease in these patients, the skin symptoms being what led them to get treatment from dermatologists in the first place. In the current study, over 80% of all patients presented first with skin disease, then with joint disease. It is also possible that the psoriatic arthritis in these patients was not being adequately treated. We know that dermatologists were treating these patients; it is uncertain whether these patients also were being treated by either rheumatologists or dermatologists for their joint conditions.
Table VI. Prior treatments for psoriatic arthritis. PsA patients (n51122) Number of patients with >1 prior PsA systemic therapy, n (%) Number of prior PsA systemic therapies used, n (%): no therapy 1 therapy 2 therapies 3 therapies 4 therapies 556 (49.6)

566 385 138 27 6

(50.4) (34.3) (12.3) (2.4) (0.5)

PsA5psoriatic arthritis; n5number of patients in intent-to-treat analysis.

One goal of this study was to observe patients with psoriatic arthritis being treated at the offices of community dermatologists. These patients generally exhibited demographic and baseline disease characteristics that were similar to that of patients being treated by dermatologists at academic centers. However, one interesting observation is the slight difference in the distribution of psoriatic arthritis subtypes between types of site. Academic sites more frequently diagnosed the milder type of joint symptom, asymmetric polyarthritis or oligoarthritis, than did community sites (67% versus 51%, Table II). In contrast, mean tender/painful and swollen joint counts, also indicators of joint disease, were greater at academic sites than at community sites (Table II). Whether these differences reflect ability or willingness of community dermatologists to perform standardized joint counts and to use definitions of psoriatic arthritis subtypes, or actual differences in the patients who receive care in the two settings, is unclear at this point. Further study of potential differences in practice patterns would help clarify this. These patients were required to have extensive skin disease (i.e. 10% or greater BSA involvement) at baseline. However, the eligibility criteria did not include a measure of lesional severity such as the physician global assessment of psoriasis, which assesses lesional erythema, thickness, and scaliness, and which is independent of extent of the disease. While most patients (approximately 80%) had moderate to severe disease based on the physician global assessment of psoriasis, some patients (20%) had mild or almost clear disease at baseline despite having extensive skin disease.

EDUCATE baseline profile Most patients had received prior treatment for skin symptoms, including topical therapies, phototherapies, and systemic therapies. Of these, only methotrexate and cyclosporine are potentially useful in the joint disease of psoriatic arthritis. Only a small minority of patients was using these at the time of entry into the study. Unfortunately, only half of the patients had ever received systemic psoriatic arthritis treatment, even after experiencing joint symptoms and disability for several years. Our data show that, similar to those who were newly diagnosed with joint disease, many patients with active, meaningful arthritic components receive no treatment to address this progressively debilitating aspect of their psoriatic arthritis. An important finding in the analysis of baseline characteristics of these patients was the observation that patient-reported quality of life measurements were disease-specific. DLQI scores correlated only with the severity of skin disease, and HAQ scores correlated only with the assessment of joint disease. Neither system can be used as a tool to simultaneously assess skin and joint disease. This trial differs from previous trials that demonstrated the efficacy and safety of etanercept in patients with psoriatic arthritis. The previous trials, conducted at rheumatology clinics, enrolled patients who had had extensive joint disease but who may have had both mild and limited skin disease at study entry (i.e. eligible patients only had to have stable psoriasis with a measurable target lesion) (18,19). In contrast, in addition to joint disease, patients enrolled in this trial had more extensive skin disease, with 10% or greater BSA involvement, and most patients (80%) had moderate to severe skin disease at baseline according to the physician global assessment of psoriasis. Baseline psoriatic arthritis disease duration in this trial was shorter than in previous trials (7 versus 9 years, respectively), and the mean tender/swollen joint count was smaller (10 versus 20 joints, respectively) (18,19). Nevertheless, the psoriatic arthritis patients recruited from dermatology clinics in this study suffered from significant joint disease, resulting in disability and reduced quality of life. It is hoped that results from this study will help to determine whether etanercept therapy will provide benefits to the patients with psoriatic arthritis, even if they have milder joint disease. Furthermore, we will determine the magnitude of skin responses in a large cohort of psoriatic arthritis patients. These baseline observations, however, provide some insight into the characteristics of patients with psoriatic arthritis being treated in dermatology clinics. There are several questions that will not be answered by this report. For example, only a subset of the psoriasis patient population was screened at entry, thus, we will not be able to generate data on the prevalence of arthritis within psoriasis patients. That said, the observation of nearly one-quarter of

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trial subjects being diagnosed after less than 1 year strongly supports the concept that psoriatic arthritis is under-recognized or under-treated. One weakness of this trial is its open-label study design; however, there are several placebo-controlled trials reported in the literature, and etanercept has been approved by the FDA and the EC for use in psoriasis and psoriatic arthritis (1719,29,30). Another possible weakness is that enthesitis and dactylitis were not assessed in these patients; this may result in the study population not reflecting all possible subtypes of psoriatic arthritis being treated in dermatology clinics, thus under-representing the full range of disease that is observed in the clinic. Additionally, the effects of therapy on these aspects of disease will not be followed. Also, the joint disease in these patients was not evaluated by a rheumatologist, thereby leaving open the possibility that they may have other concurrent arthritic conditions that can affect joint assessments, a possibility that may affect subsequent analyses of treatment response. For example, patients with concurrent osteoarthritis may exhibit less apparent effects with treatment. Similarly, these patients have not been assessed using any imaging technology (i.e. magnetic resonance imaging and radiographs), which may contribute to an inaccurate representation of the prevalence of spinal involvement and will not allow documentation of the extent of arrest of disease progression. Furthermore, one possible weakness of the study, especially when efficacy is assessed, is that patients could meet the entry criteria with extensive (by BSA) yet mild or even almost clear (by lesional severity) psoriasis. Data from our study and others (28) suggest that joint disease in psoriatic arthritis patients with psoriasis is not being consistently diagnosed or treated. Although our study does not explore reasons, possible explanations might include patients not recognizing the significance of joint symptoms, dermatologists not examining or inquiring for signs or symptoms of psoriatic arthritis, or dermatologists not understanding the significance of these signs and symptoms. A first step might be for dermatologists to ask their psoriasis patients about any joint pain or stiffness and to examine for signs of joint disease while performing the cutaneous examination. Thereafter, depending on an individual dermatologists knowledge and comfort with the diagnosis and treatment of psoriatic arthritis, and patient presentation, patients may be managed by their dermatologists or may be referred to a rheumatologist for evaluation. Regardless, data presented in this manuscript suggest that significant joint disease is currently under-diagnosed and under-treated among patients with psoriatic arthritis being treated in dermatology offices. In conclusion, psoriatic arthritis, once considered to be a fairly benign condition, is now known to be a

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A. B. Gottlieb et al. Inc.; Aventis; Biogen, Inc.; Boehringer Ingelheim; Centocor, Inc; Genentech, Inc.; Idec Pharmaceuticals; Merck & Co, Inc.; Novartis; Pfizer Inc.; Pharmacia; Serono; Wyeth Pharmaceuticals; and Xoma. Dr Jackson has received honoraria, grants, and research support from Amgen, and has served as a consultant for Amgen. Dr Eisen has not received any other corporate funding. Drs Xia, Asare, and Stevens are employees of Amgen; Dr Stevens is an Amgen stockholder.

progressive disease (2), even in its early stages (1). Patients with a polyarticular onset are at a particularly high risk of erosive and deforming disease (31). The proportion of patients with spinal disease increases with longer duration of psoriatic arthritis (11). The high degree of co-existing axial and peripheral disease in this cohort also suggests the need for earlier diagnosis and treatment. In one study, the probability of requiring musculoskeletal reconstructive surgery was 7% in patients with psoriatic arthritis and the probability of surgery increased with disease duration (32). Other complications of psoriatic arthritis include cardiovascular abnormalities (33), alterations in lipid metabolism (34), uveitis (35), and renal abnormalities (36). Nail disease is common in patients with distal interphalangeal joint disease (37,38). Many patients progress through several psoriatic arthritis subtypes, and with the exception of the association of erosive disease and polyarticular onset, the pattern of joint disease at onset cannot be used to predict complications or progression (11,34). Consistent with the current understanding of the inflammatory nature of psoriatic arthritis, significant inflammation at presentation was predictive of disease progression in a multivariate relative risk model (39). Psoriatic arthritis is a severe and debilitating condition that is associated with significant morbidity. The advent of new therapies that can prevent joint destruction offers an opportunity for dermatologists to prevent disability by intervening early in the course of psoriatic arthritis. Acknowledgments We thank all of the individual physicians and their study staff, as well as the subjects of this trial for their thoughtful participation. We thank Julia Gage, PhD, and Helen M. Wilfehrt, PhD, who provided assistance in preparing this article. The data presented here are from a clinical trial sponsored by Immunex Corporation, a wholly owned subsidiary of Amgen Inc. (Thousand Oaks, CA, USA). Amgen Inc. and its investigators, including authors of this article, designed the study. Financial disclosure Drs Gottlieb, Jackson, and Eisen were investigators on this study. Dr Gottlieb is a consultant for several companies (Amgen Inc.; BiogenIdec, Inc; Centocor, Inc.; Wyeth Pharmaceuticals; Schering-Plough Corporation; Eisai; Celgene Corp.; Bristol Myers Squibb Co.; Beiersdorf, Inc.; Warner Chilcott; Abbott Labs.; Roche; Sankyo; Medarex; Kemia; Celera; TEVA; Actelion; UCB; Novo Nordisk; Almirall; Immune Control) and is on the speakers bureau for Amgen Inc. and Wyeth Pharmaceuticals. Dr Mease is advisor, and/or participant in the speakers bureau for Abbott Laboratories; Amgen

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