Clinical Caracteristic

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ORIGINAL ARTICLE

Clinical characteristics of psoriatic arthritis and psoriasis indermatologists offices

ALICE B. GOTTLIEB1, PHILIP J. MEASE2, J. MARK JACKSON3, DRORE EISEN4,

H. AMY XIA5, CHARLES ASARE5 & SETH R. STEVENS5

1Department of Dermatology, TuftsNew England Medical Center, Boston, MA, USA,

2Seattle Rheumatology Associates,

Seattle, WA, USA,3

Dermatology Specialists, Louisville, KY, USA,4

Dermatology Research Associates, Cincinnati, OH,

USA, and5Amgen Inc., Thousand Oaks, CA, USA

AbstractObjective: 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 patientsexperienced 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, patientdemographics 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 oftheir skin disease. Baseline skin and joint disease measures were not correlated. Psoriatic arthritis was newly diagnosed in23% of the patients. Most had received prior therapy for psoriasis, but only half had received systemic therapy for psoriaticarthritis. Conclusion: Assessment for joint disease in psoriasis patients being treated at dermatology clinics may facilitateearlier 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% ofpsoriatic 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 improve-

ment, 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 demon-strate 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: [email protected]

Journal of Dermatological Treatment. 2006; 17: 279287


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of psoriasis have been largely ineffective at prevent-

ing 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 membrane-

bound 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 progressionof 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 dermatol-

ogists may lead to its earlier diagnosis and initiation

of therapy, therefore preventing disability and

progression of the disease.

This report describes the demographic and base-

line characteristics of patients enrolled in a large

Phase 4, open-label, primarily community-based

clinical trial, named Experience Diagnosing,

Understanding Care, and Treatment withEtanercept (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 17academia-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

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 indermatology clinics. The institutional review boards

of the participating sites approved the study proto-

col, 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 stiff-

ness 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 involve-

ment, history (duration) of skin disease, and treat-

ments. 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 assess-

ments at baseline consisted of Patient GlobalAssessment 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-DIscore (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 HAQ-

DI 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). HAQ-

DI scores range from 0 to 3 with 0 indicating

280 A. B. Gottlieb et al.


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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 mea-

sures for skin disease (DLQI) and joint disease and

patient assessments for both conditions were per-

formed using Spearman rank correlations. Linear

regression analyses were used to examine the

relationships between baseline quality of life mea-

sures and patient assessments of disease.

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 community-

based dermatology clinics and 191 patients were

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 aca-

demic and community dermatology sites; therefore,

characteristics are described for all patients com-

bined, 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 weredisabled (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-

Table I. Patient characteristics.

PsA patients by site type

Academic sites Community sites All sites

(n5191) (n5931) (n51122)

Age, mean, years (SD) 48.3 (12.5) 47.9 (13.6) 48.0 (13.4)

Age, range, years 1977 1888 1888

Sex, n, males (%) 105 (55.0) 507 (54.5) 612 (54.5)

Race, n, white (%) 155 (81.2) 793 (85.2) 948 (84.5)

Height, mean, cm (SD) 170.6 (11.3) 170.9 (11.2) 170.8 (11.2)

Height, range, cm 142196 127206 127206

Weight, mean, kg (SD) 90.7 (23.1) 89.6 (22.0) 89.8 (22.1)

Weight, range, kg 46.8158.5 43.7198.0 43.7198.0

Highest level of education, n (%)Grades K8 5 (2.6) 23 (2.5) 28 (2.5)

Grades 912 or GED 36 (18.8) 304 (32.7) 340 (30.3)

Technical school 10 (5.2) 39 (4.2) 49 (4.4)

Some college 48 (25.1) 230 (24.7) 278 (24.8)

College 58 (30.4) 233 (25.0) 291 (25.9)

Postgraduate 34 (17.8) 102 (11.0) 136 (12.1)

Employment status, n (%)

Full-time (w35 hours per

week)

115 (60.2) 561 (60.3) 676 (60.2)

Part-time (v35 hours per

week)

21 (11.0) 82 (8.8) 103 (9.2)

Temporarily disabled 2 (1.0) 3 (0.3) 5 (0.4)

Disabled 10 (5.2) 37 (4.0) 47 (4.2)

Retired 24 (12.6) 144 (15.5) 168 (15.0)

Unemployed 14 (7.3) 85 (9.1) 99 (8.8)Other 5 (2.6) 19 (2.0) 24 (2.1)

P A i i h i i b f i i i l i SD d d d i i i i i

EDUCATE baseline profile 281


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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 II. Patient disease characteristics.



(n5191) (n5931) (n51122)

Skin disease characteristicsDuration of psoriasis, mean, years (SD) 20.9 (13.5) 18.6 (12.70) 19.0 (12.9)

BSA affected by psoriasis, mean, % (SD) 24.0 (17.3) 27.4 (19.8) 26.8 (19.4)

BSA affected by psoriasis, range, % 10.090.0 10.091.0 10.091.0

Physician global assessment of psoriasis, n (%)

Almost clear 3 (1.6) 25 (2.7) 28 (2.5)

Mild 29 (15.2) 171 (18.4) 200 (17.8)

Moderate 98 (51.3) 512 (55.0) 610 (54.4)

Marked 50 (26.2) 191 (20.5) 241 (21.5)

Severe 11 (5.8) 32 (3.4) 43 (3.8)

Joint disease characteristics

Duration of PsA, mean, years (SD) 7.7 (8.9) 7.1 (8.2) 7.2 (8.3)

PsA subtypea, n (%)

Asymmetric polyarthritis or

oligoarthritis

128 (67.0) 471 (50.6) 599 (53.4)

Symmetric polyarthritis 49 (25.7) 462 (49.6) 511 (45.5)Spondyloarthritis 53 (27.7) 285 (30.6) 338 (30.1)

Distal interphalangeal joint disease 61 (31.9) 398 (42.7) 459 (40.9)

Arthritis mutilans 4 (2.1) 23 (2.5) 27 (2.4)

Tender/painful joint count, n, mean (SD) 14.1 (17.2) 9.0 (8.7) 9.9 (10.8)

Tender/painful joint count, range 071 060 071

Swollen joint count, n (SD) 8.4 (10.8) 5.0 (6.0) 5.6 (7.2)

Swollen joint count, range 058 060 060

Spondylitis present, n (%) 50 (26.2) 291 (31.3) 341 (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.

Table III. Patient-reported assessment of disease.



(n5191) (n5931) (n51122)

Skin disease assessment

Global Assessment of Psoriasis,

mean score (SD)

4.1 (0.9) 3.9 (1.0) 4.0 (1.0)

Global Assessment of Psoriasis,

range

15 15 15

Itching, mean score (SD) 3.8 (1.2) 3.6 (1.3) 3.6 (1.3)

DLQI, mean score (SD) 14.3 (7.0) 13.9 (6.9) 13.9 (6.9)

Joint disease assessment

Global Assessment of Joint Disease,

mean score (SD)

3.0 (1.0) 2.8 (1.1) 2.8 (1.1)

Global Assessment of Joint Pain,

mean score (SD)

4.9 (2.2) 4.5 (2.3) 4.6 (2.3)

Duration of morning stiffness,

median, min/day (range)

90.0 (0720) 90.0 (0720) 90.0 (0720)

HAQ Disability Domain, mean score(SD)

0.85 (0.6) 0.78 (0.6) 0.79 (0.6)

P A i i h i i b f i i i l i SD d d d i i DLQI D l Lif Q li I d



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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 representedin 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 patient-

reported 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 assessedby DLQI, correlated with patient assessments of skin

disease (Spearman rank correlation r50.47;

pv0.0001). Similarly, HAQ-DI measurements cor-

related with patient assessments of joint disease

(r50.48; pv0.0001). These correlations were dis-

ease-specific; however, there was no correlation

between patient assessments of joint disease and

DLQI (r50.20; p50.29), or between patient assess-

ments 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, respec-

tively (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 photother-

apy, 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 corti-

costeroids (56%) and vitamin D analogs (52%).

These data demonstrate that, despite meaningfullyactive 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

(n5

931), rather than at academic dermatologistoffices (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.



(n5191) (n5931) (n51122)

Skin then joint (%) 165 (86.4) 777 (83.5) 942 (84.0)Joint then skin (%) 2 (1.0) 33 (3.5) 35 (3.1)

Simultaneous (%) 24 (12.6) 119 (12.8) 143 (12.7)



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observation suggests a possible under-recognition or

undertreatment of psoriatic arthritis, which has beendescribed 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 dermatologistsfor their joint conditions.

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 char-

acteristics that were similar to that of patients being

treated by dermatologists at academic centers.

However, one interesting observation is the slightdifference 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

Table V. Prior treatments for psoriasis.

PsA patients

(n51122)

Systemic therapies, n (%)

Number of patients with >1 prior psoriasis

systemic therapy

652 (58.1)

Number of prior psoriasis systemic therapies

used:

no therapy 470 (41.9)

1 therapy 363 (32.4)

2 therapies 214 (19.1)



5 therapies 2 (0.2)

Phototherapies n (%)

Number of patients with >1 prior phototherapy 565 (50.4)

Number of prior phototherapies used:


1 therapy 439 (39.1)


Topical therapies, n (%)Number of patients with >1 prior topical therapy 941 (83.9)

Number of prior topical therapies used:


1 therapy 277 (24.7)




>5 therapies 86 (7.7)

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

arthritis.

Table VI. Prior treatments for psoriatic arthritis.

PsA patients

(n51122)

Number of patients with >1 prior PsA systemic

therapy, n (%)

556 (49.6)

Number of prior PsA systemic therapies used, n

(%):


1 therapy 385 (34.3)


3 therapies 27 (2.4)4 therapies 6 (0.5)

P A i i h i i b f i i i

Table VII. Select therapies by type used for psoriasis or psoriatic

arthritis before enrollment in the study.

PsA patients

(n51122)

Systemic therapies, n (%)

Methotrexate 431 (38.4)NSAIDs 319 (28.4)

Corticosteroids 215 (19.2)

Oral retinoids 132 (11.8)

Cyclosporine 103 (9.2)

Sulfasalazine 32 (2.9)

Hydroxychloroquine 12 (1.1)

Topical therapies n (%)

Topical corticosteroids 632 (56.3)

Vitamin D analogs 587 (52.3)

Tar compounds 396 (35.3)

Vitamin A analogs 143 (12.7)

Phototherapies, n (%)

PUVA 254 (22.6)

UVB 436 (38.9)

PsA5psoriatic arthritis; n5number of patients in the intent-to-

treat analysis; NSAIDs5non-steroidal anti-inflammatory drugs;

PUVA5p s or a le n p l us u l tr a vi o le t A r a di a ti o n t h er a py ;

UVB5ultraviolet B radiation.



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Most patients had received prior treatment for

skin symptoms, including topical therapies, photo-

therapies, 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 onlywith 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 simulta-

neously assess skin and joint disease.

This trial differs from previous trials that demon-

strated 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). Incontrast, 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 assess-

ment 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 psor-

iatic 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 pro-

vide 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

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 canaffect 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 reso-

nance imaging and radiographs), which may con-

tribute 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 thatpatients 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 dermatolo-

gists knowledge and comfort with the diagnosis and

treatment of psoriatic arthritis, and patient presenta-

tion, patients may be managed by their dermatolo-

gists or may be referred to a rheumatologist for

evaluation. Regardless, data presented in this manu-

script suggest that significant joint disease is cur-

rently under-diagnosed and under-treated among

patients with psoriatic arthritis being treated in

dermatology offices.

In conclusion psoriatic arthritis once considered



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progressive disease (2), even in its early stages (1).

Patients with a polyarticular onset are at a particu-

larly 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 compli-

cations 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 interpha-

langeal joint disease (37,38). Many patients progress

through several psoriatic arthritis subtypes, and with

the exception of the association of erosive diseaseand 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 psor-

iatic arthritis, significant inflammation at presenta-

tion 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 subsidi-

ary of Amgen Inc. (Thousand Oaks, CA, USA).

Amgen Inc. and its investigators, including authorsof 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

Inc.; Aventis; Biogen, Inc.; Boehringer Ingelheim;

Centocor, Inc; Genentech, Inc.; Idec Pharm-

aceuticals; 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.

References

1. Kane D, Stafford L, Bresnihan B, FitzGerald O. A

prospective, clinical and radiological study of early psoriatic

arthritis: an early synovitis clinic experience. Rheumatology

(Oxford). 2003;42:14608.

2. McHugh NJ, Balachrishnan C, Jones SM. Progression of

peripheral joint disease in psoriatic arthritis: a 5-yr prospectivestudy. Rheumatology (Oxford). 2003;42:77883.

3. Husted JA, Gladman DD, Farewell VT, Cook RJ. Health-

related quality of life of patients with psoriatic arthritis: a

comparison with patients with rheumatoid arthritis. Arthritis

Rheum. 2001;45:1518.

4. Sokoll KB, Helliwell PS. Comparison of disability and quality

of life in rheumatoid and psoriatic arthritis. J Rheumatol.

2001;28:18426.

5. Zachariae H, Zachariae R, Blomqvist K, Davidsson S,

Molin L, Mork C, et al. Quality of life and prevalence of

arthritis reported by 5,795 members of the Nordic Psoriasis

Associations. Data from the Nordic Quality of Life Study.

Acta Derm Venereol. 2002;82:10813.

6. Biondi Oriente C, Scarpa R, Pucino A, Oriente P. Psoriasis

and psoriatic arthritis. Dermatological and rheumatologicalco-operative clinical report. Acta Derm Venereol Suppl

(Stockh). 1989;146:6971.

7. Leonard DG, ODuffy JD, Rogers RS. Prospective analysis of

psoriatic arthritis in patients hospitalized for psoriasis. Mayo

Clin Proc. 1978;53:51118.

8. Scarpa R, Oriente P, Pucino A, Torella M, Vignone L,

Riccio A, et al. Psoriatic arthritis in psoriatic patients.

Br J Rheumatol. 1984;23:24650.

9. Shbeeb M, Uramoto KM, Gibson LE, OFallon WM,

Gabriel SE. The epidemiology of psoriatic arthritis in

Olmsted County, Minnesota, USA, 19821991.

J Rheumatol. 2000;27:124750.

10. Husted JA, Gladman DD, Long JA, Farewell VT. A modified

version of the Health Assessment Questionnaire (HAQ) for

psoriatic arthritis. Clin Exp Rheumatol. 1995;13:43943.

11. Brockbank J, Gladman D. Diagnosis and management of

psoriatic arthritis. Drugs. 2002;62:244757.

12. Harrison BJ, Silman AJ, Barrett EM, Scott DG,

Symmons DP. Presence of psoriasis does not influence the

presentation or short-term outcome of patients with early

inflammatory polyarthritis. J Rheumatol. 1997;24:17449.

13. Mease PJ. Tumour necrosis factor (TNF) in psoriatic

arthritis: pathophysiology and treatment with TNF inhibitors.

Ann Rheum Dis. 2002;61:298304.

14. Mehlis SL, Gordon KB. The immunology of psoriasis and

biologic immunotherapy. J Am Acad Dermatol.

2003;49:S4450.

15. Ettehadi P, Greaves MW, Wallach D, Aderka D, Camp RD.

Elevated tumour necrosis factor-alpha (TNF-alpha) biologi-cal activity in psoriatic skin lesions. Clin Exp Immunol.

1994;96:14651.

P h G S i G L b BF D k A B ll H S l JS



9/10

other proinflammatory cytokines in psoriatic arthritis synovial

fluid. J Rheumatol. 1997;24:51823.

17. Mease P. TNFalpha therapy in psoriatic arthritis and

psoriasis. Ann Rheum Dis. 2004;63:7558.

18. Mease PJ, Goffe BS, Metz J, VanderStoep A, Finck B,

Burge DJ. Etanercept in the treatment of psoriatic arthritis

and psoriasis: a randomised trial. Lancet. 2000;356:38590.

19. Mease PJ, Kivitz AJ, Burch FX, Siegel EL, Cohen SB, Ory P,et al. Etanercept treatment of psoriatic arthritis: safety,

efficacy, and effect on disease progression. Arthritis Rheum.

2004;50:226472.

20. EnbrelH (etanercept) Full Prescribing Information,

Thousand Oaks, CA: Amgen Inc. and Wyeth-Ayerst

Pharmaceuticals; 2006.

21. Langley RG, Ellis CN. Evaluating psoriasis with Psoriasis

Area and Severity Index, Psoriasis Global Assessment, and

Lattice System Physicians Global Assessment. J Am Acad

Dermatol. 2004;51:5639.

22. Finlay AY, Coles EC. The effect of severe psoriasis on the

quality of life of 369 patients. Br J Dermatol. 1995;132:

23644.

23. Shikiar R, Bresnahan BW, Stone SP, Thompson C, Koo J,

Revicki DA. Validity and reliability of patient reportedoutcomes used in psoriasis: results from two randomized

clinical trials. Health Qual Life Outcomes. 2003;1:53.

24. Cheah SY, Clark C, Goldberg L, Li Wan Po A, Phillips R.

Outcome measures, pooled index and quality of life instru-

ments in rheumatoid arthritis. J Clin Pharm Ther.

1996;21:297316.

25. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of

patient outcome in arthritis. Arthritis Rheum. 1980;23:

13745.

26. Scott DL, Garrood T. Quality of life measures: use and

abuse. Baillieres Best Pract Res Clin Rheumatol.

2000;14:66387.

27. Gladman DD, Helliwell P, Mease PJ, Nash P, Ritchlin C,

Taylor W. Assessment of patients with psoriatic arthritis: a

review of currently available measures. Arthritis Rheum.2004;50:2435.

28. Alenius GM, Stenberg B, Stenlund H, Lundblad M,

Dahlqvist SR. Inflammatory joint manifestations are pre-

valent in psoriasis: prevalence study of joint and axial

involvement in psoriatic patients, and evaluation of a psoriatic

and arthritic questionnaire. J Rheumatol. 2002;29:257782.

29. Gottlieb AB, Matheson RT, Lowe N, Krueger GG, Kang S,

Goffe BS, et al. A randomized trial of etanercept as

monotherapy for psoriasis. Arch Dermatol.

2003;139:162732; discussion 1632.

30. Leonardi CL, Powers JL, Matheson RT, Goffe BS, Zitnik R,

Wang A, et al. Etanercept as monotherapy in patients withpsoriasis. N Engl J Med. 2003;349:201422.

31. Queiro-Silva R, Torre-Alonso JC, Tinture-Eguren T, Lopez-

Lagunas I. A polyarticular onset predicts erosive and

deforming disease in psoriatic arthritis. Ann Rheum Dis.

2003;62:6870.

32. Zangger P, Gladman DD, Bogoch ER. Musculoskeletal

surgery in psoriatic arthritis. J Rheumatol. 1998;25:7259.

33. Saricaoglu H, Gullulu S, Bulbul Baskan E, Cordan J,

Tunali S. Echocardiographic findings in subjects with

psoriatic arthropathy. J Eur Acad Dermatol Venereol.

2003;17:41417.

34. Jones SM, Harris CP, Lloyd J, Stirling CA, Reckless JP,

McHugh NJ. Lipoproteins and their subfractions in psoriatic

arthritis: Identification of an atherogenic profile with active

joint disease. Ann Rheum Dis. 2000;59:9049.35. Queiro R, Torre JC, Belzunegui J, Gonzalez C, De Dios JR,

Unanue F, et al. Clinical features and predictive factors in

psoriatic arthritis-related uveitis. Semin Arthritis Rheum.

2002;31:26470.

36. Alenius GM, Stegmayr BG, Dahlqvist SR. Renal abnormal-

ities in a population of patients with psoriatic arthritis.

Scand J Rheumatol. 2001;30:2714.

37. Jones SM, Armas JB, Cohen MG, Lovell CR, Evison G,

McHugh NJ. Psoriatic arthritis: Outcome of disease subsets

and relationship of joint disease to nail and skin disease.

Br J Rheumatol. 1994;33:8349.

38. Williamson L, Dalbeth N, Dockerty JL, Gee BC,

Weatherall R, Wordsworth BP. Extended report: nail disease

in psoriatic arthritis clinically important, potentially

treatable and often overlooked. Rheumatology (Oxford).2004;43:7904.

39. Gladman DD, Farewell VT, Nadeau C. Clinical indicators of

progression in psoriatic arthritis: Multivariate relative risk

model. J Rheumatol. 1995;22:6759.



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