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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: agottlieb@tufts-nemc.org
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
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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.
PsA patients by site type
Academic sites Community sites All sites
(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.
PsA patients by site type
Academic sites Community sites All sites
(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.
PsA patients by site type
Academic sites Community sites All sites
(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)
3 therapies 62 (5.5)
4 therapies 11 (1.0)
5 therapies 2 (0.2)
Phototherapies n (%)
Number of patients with >1 prior phototherapy 565 (50.4)
Number of prior phototherapies used:
no therapy 557 (49.6)
1 therapy 439 (39.1)
2 therapies 126 (11.2)
Topical therapies, n (%)Number of patients with >1 prior topical therapy 941 (83.9)
Number of prior topical therapies used:
no therapy 181 (16.1)
1 therapy 277 (24.7)
2 therapies 265 (23.6)
3 therapies 203 (18.1)
4 therapies 110 (9.8)
>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
(%):
no therapy 566 (50.4)
1 therapy 385 (34.3)
2 therapies 138 (12.3)
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.
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