Journal of Dermatological Treatment

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Psoriatic arthritis for dermatologists

Alice Gottlieb & Joseph F. Merola

To cite this article: Alice Gottlieb & Joseph F. Merola (2020) Psoriatic arthritis
for dermatologists, Journal of Dermatological Treatment, 31:7, 662-679, DOI:
10.1080/09546634.2019.1605142

To link to this article: https://doi.org/10.1080/09546634.2019.1605142

© 2019 The Author(s). Published with

license by Taylor & Francis Group, LLC

Published online: 07 May 2019.

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JOURNAL OF DERMATOLOGICAL TREATMENT
2020, VOL. 31, NO. 7, 662–679
https://doi.org/10.1080/09546634.2019.1605142

REVIEW ARTICLE

Psoriatic arthritis for dermatologists

Alice Gottlieba and Joseph F. Merolab
a
Department of Dermatology, Icahn School of Medicine at Mt Sinai, New York, NY, USA; bDepartment of Medicine, Division of Rheumatology
and Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

ABSTRACT ARTICLE HISTORY

Psoriatic arthritis (PsA) affects up to one-third of patients with psoriasis. It is the major comorbidity of Received 27 March 2019
psoriasis because of the likelihood that loss of function and permanent disability will develop if initiation Accepted 28 March 2019
of treatment is delayed. Dermatologists are uniquely positioned to recognize early signs of PsA and be
KEYWORDS
the first-line healthcare practitioners to detect PsA in patients with psoriasis. PsA can affect six clinical
Psoriatic arthritis; psoriasis;
domains: peripheral arthritis, dactylitis, enthesitis, psoriasis, psoriatic nail disease, and axial disease. peripheral arthritis;
However, not every patient will have involvement of all domains and the domains affected can change dactylitis; enthesitis;
over time. Complicating the diagnosis is the condition’s similarity with other arthritic diseases and poten- psoriatic nail disease; axial
tial heterogeneity. In this article, we provide practical guidance for dermatologists for detecting PsA in disease; disability; loss
patients with psoriasis. We also review the available treatment options by each clinical domain of PsA of function
and give advice on how to interpret the results of PsA clinical trials. Through early recognition of PsA in
patients with psoriasis and initiation of proper treatment, dermatologists can help to prevent PsA disease
progression, irreversible joint damage, and resultant permanent disability, and improve quality of life.

Introduction with first- and second-degree relatives of affected individuals hav-

Psoriatic arthritis (PsA) is a potentially progressive, erosive,
chronic, heterogeneous, and systemic inflammatory disease that
develops in up to 30% of patients with psoriasis and can manifest
in up to six different clinical domains, including peripheral arth-
ritis, dactylitis, enthesitis, psoriasis, psoriatic nail disease, and axial
disease (1–3). Peripheral arthritis can cause pain in a variety of
joints in PsA and commonly involves the knee (41%), finger
(26%), hip (19%), ankle (19%), and wrist (16%) (3). Dactylitis is col-
loquially referred to as ‘sausage digit,’ and is a distinguishing fea-
ture of PsA, characterized by uniform swelling of an entire digit
that occurs in up to 48% of patients (4). Another distinguishing
feature of PsA, enthesitis is present in 35% of patients and is
defined as inflammation where the tendon, ligament, or joint cap-
sule inserts into bone (5–7). Psoriatic lesions can develop on the
skin and may affect the nails (e.g. pitting). Axial symptoms, which
may occur in up to 50% of patients with PsA, result in back stiff-
ness and pain that improves with movement (8,9).
Etiologically, the familial aggregation of psoriasis and PsA is
indicative of a genetic basis for psoriatic disease. The major
histocompatibility complex is a known susceptibility locus for PsA
and psoriasis (10–12), as shown by the observation that nearly
25% of patients with PsA are positive for human leukocyte
antigen (HLA)-B
27 (13). Specific HLA alleles are associated with
different PsA manifestations, including symmetric sacroiliitis
(HLA-B
27:05), asymmetric sacroiliitis (HLA-B
08:01 and HLA-
C
07:01), enthesitis (HLA-B
27:05 and HLA-C
01:02), dactylitis
(HLA-B
27:05 and HLA-B
08:01), and synovitis (HLA-B
08:01) (14).
HLA-Cw
0602 is more common in PsA than the general
population and is associated with an earlier age of psoriasis onset
(15). Additionally, there is a strong familial aggregation of PsA
ing increased risk of PsA (16,17).
The pathophysiology of PsA is similar to that of psoriasis and
involves important cytokines in the interleukin (IL)-23-Th17-IL-17
and tumor necrosis factor (TNF) pathway (e.g. IL-12, IL-17, IL-23,
and TNF-a), as well as cytokines such as IL-22 (13,18,19). Thus, it
is not surprising that many cytokine-targeting biologics and
small-molecule inhibitors that provide effective skin clearance in
psoriasis also improve joint symptoms and slow radiographic pro-
gression in PsA.
Although PsA is a widely recognized comorbidity in psoriasis,
nearly 52% of patients with psoriasis have joint pain without a
diagnosis of PsA and the average diagnostic delay for PsA is
5 years (3,20). Dermatologists have an essential role in reducing
this diagnostic delay by screening patients with psoriasis for PsA,
as 85% of patients develop psoriasis before PsA, and in these
cases, PsA frequently develops within 10 years following the
appearance of psoriasis (21–23). There are a number of comorbid-
ities that are more common in patients with PsA than in patients
with psoriasis without signs of PsA, including inflammatory bowel
disease, cardiovascular diseases (including obesity, hypertension,
and type 2 diabetes mellitus), uveitis, depression, anxiety, and
fatty liver disease (24,25). Thus, this indicates a need for screening
all patients with psoriasis.
Early detection and treatment of PsA are critically important
for improving long-term patient outcomes, as the disease can
progress rapidly and cause irreversible joint damage (21,26).
Specifically, diagnostic and treatment delays of more than
6 months contribute to peripheral joint erosions and poor func-
tional outcomes (27). When PsA is identified early, initiation of
treatment with targeted therapies can significantly improve the

CONTACT Alice Gottlieb alicegottliebderm@gmail.com Department of Dermatology, Icahn School of Medicine at Mt Sinai, 10 Union Square East, New York,
NY, USA
ß 2019 The Author(s). Published with license by Taylor & Francis Group, LLC
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/),
which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in
any way.

signs and symptoms of PsA and prevent radiographic progres-
sion (28–30).
The remainder of this review will provide dermatologists with
practical insights into how to recognize the varied clinical mani-
festations of PsA, properly diagnose PsA, and interpret results
from clinical trials of PsA.
Diagnosis of PsA
Inflammatory versus non-inflammatory arthritis
Recognizing subtle symptomatic differences between inflamma-
tory and non-inflammatory arthritis is critical for proper diagnosis,
as these diseases share similar characteristics such as pain and
joint stiffness. In general, clinical characteristics of inflammatory
arthritis include prolonged stiffness upon immobility, joint pain,
joint tenderness, joint swelling, pain at entheses, swollen digits,
and worsened back pain upon immobility (9,31). Patients with
non-inflammatory arthritis typically present with normal acute-
phase reactants, bony crepitus, asymmetric joint involvement, dis-
tal interphalangeal (DIP) joint involvement, a lack of prolonged
morning stiffness, and bony outgrowths around the joints (9,31).
Of note, non-inflammatory arthritis may be suspected in patients
with PsA because inflammatory markers are normal in 50% of
patients with PsA and DIP involvement in PsA may be confused
with osteoarthritis on plain radiography (31,32). Questions to help
practitioners identify inflammatory arthritis are presented in
Table 1.
Clinical diagnosis of PsA
A simple mnemonic, ‘PSA,’ representing pain (in the joints), stiff-
ness (>30 min after inactivity/sausage digit [dactylitis]), and axial
(axial spine involvement/back pain associated with stiffness and
pain that improves with activity), has been developed as a con-
venient method to help practitioners quickly recognize specific
characteristics of PsA (9). Enthesitis may present before symptoms
of arthritis in individuals with PsA, and early enthesitis is not
detectable by radiography. Thus, because enthesitis may be the
only presenting musculoskeletal symptom of PsA, it is important
for dermatologists to query patients regarding enthesitis symp-
toms. During clinical examinations, dermatologists can screen for
visible signs of enthesitis such as redness and swelling at insertion
sites (33). Although enthesitis is typically evaluated by manual
palpation, it is particularly challenging to assess because objective
signs of inflammation such as redness and swelling are often
absent and symptoms of enthesitis are known to mimic those of
fibromyalgia, which is also associated with pain on digital palpa-
tion at tender points (34–37). Evaluation of enthesitis is a chal-
lenge amongst dermatologists and rheumatologists due to these
issues and additional education on techniques for evaluating
enthesitis would be beneficial. We suggest to first ask about pain
Table 1. Questions to ask patients to help identify the presence of inflamma-
tory arthritis.
‘Yes’ supports the presence of inflammatory arthritis
 Do you have a family history of psoriasis or psoriatic arthritis?
 Have you ever had tender/swollen fingers or toes?
 Do you experience morning stiffness lasting longer than a half hour
to 1 h?
 Does your pain improve with exercise?
 Have your symptoms of joint pain persisted for > 3 months?
 Does your pain improve with nonsteroidal anti-inflammatory drugs?
 How would you describe your pain (gnawing, throbbing, deep)?
JOURNAL OF DERMATOLOGICAL TREATMENT 663
at the more commonly affected entheses (lateral epicondyle, med-
ial femoral condyle, and Achilles tendon insertion) and then pal-
pate and look for signs of inflammation (Figure 1). Somatic
symptoms and tender point counts can help differentiate PsA
from fibromyalgia, in which patients have more tender points and
greater enthesitis scores (37). Detecting diffuse tenderness in soft
tissue areas away from joints and entheses is also helpful in differ-
entiating fibromyalgia from PsA. Patients with reactive arthritis
can also exhibit enthesitis that commonly involves the Achilles
tendon and plantar fascia (38). Other factors that can help to dif-
ferentiate reactive arthritis from PsA include younger age at onset,
sacroiliitis, and articular symptoms primarily affecting the lower
limbs and the presence of acute anterior uveitis, dysuria, or diar-
rhea/inflammatory bowel disease (38). Being cognizant of these
differences, a diagnosis of reactive arthritis or PsA requires rheu-
matologic evaluation and the dermatologist will have benefited
the patient greatly even if the diagnosis is reactive arthritis rather
than PSA.
Although PsA is a type of inflammatory arthritis, it may be
challenging to identify, because its symptoms may mimic non-
inflammatory arthritis. More specifically, in patients with PsA,
the erythrocyte sedimentation rate (ESR) and C-reactive protein
(CRP) level are within the normal range nearly 50% of the time,
joints are affected asymmetrically, DIP joint involvement may
be present, and radiographic manifestations include new bone
formation and concurrent bone loss as opposed to only bony
erosion (13,31,32,39,40). Characteristics that can help dermatol-
ogists differentiate PsA from non-inflammatory arthritis (osteo-
arthritis), inflammatory arthritis (gout and rheumatoid arthritis
[RA]), and pain (fibromyalgia) are described in Table 2. These
characteristics, however, can be challenging to differentiate
when two or more diseases are present simultaneously, and
osteoarthritis and/or fibromyalgia can present with PsA (41,42).
Practitioners should also be aware that the risk of gout is sig-
nificantly increased in patients with concurrent PsA and
psoriasis (43).
To address the need for early screening tools to identify PsA
in patients with psoriasis, three validated screening tools exist:
the psoriasis and epidemiology screening tool (PEST), the psori-
atic arthritis screening and evaluation (PASE), and the Toronto
psoriatic arthritis screening (ToPAS) (44–48). PEST is a patient
self-assessment tool consisting of five questions and a drawing
of a mannequin diagram on which patients indicate locations of
stiff, swollen, or painful joints (49,50). PASE is a questionnaire of
15 items designed specifically for use in dermatology clinics to
identify patients with psoriasis and symptoms of inflammatory
musculoskeletal disease (44,51,52). ToPAS is a 12-item question-
naire in which patients use pictures of psoriatic skin, nail disease,
inflamed joints, and dactylitis to identify symptoms (49). In a
comparison of these tools, PEST, the only nonproprietary screen-
ing tool and available on the free GRAPPA mobile phone app,
and ToPAS had slightly better sensitivity than PASE in detecting
PsA in patients with psoriasis; however, all questionnaires had
high false-positive rates, resulting in low specificity (53).
Although screening tools can be useful in some circumstances,
they are often inconvenient and challenging to include during
routine office visits with patients (9). Additionally, it is important
for dermatologists to first recognize the presence of inflammatory
arthritis before attempting differential diagnosis for PsA so that
other causes of joint pain are not overlooked.
The ClASsification criteria for Psoriatic ARthritis (CASPAR) crite-
ria, which were developed to standardize enrollment in PsA clin-
ical trials, can help dermatologists identify patients with PsA but
664 A. GOTTLIEB AND J. F. MEROLA
Figure 1. Enthesitis sites evaluated by clinical assessment instruments. LEI: Leeds Enthesitis Index; MASES: Maastricht Ankylosing Spondylitis Enthesitis Score; SPARCC:
Spondyloarthritis Research Consortium of Canada.
For scoring purposes, the inferior patella and tibial tuberosity are considered one site because of their anatomical
proximity. Image from Mease 2017 (178).
are not required for diagnosis (54). The diagnosis of PsA is clinical
and based on patient history and physical examination and sup-
ported by imaging and laboratory evaluation. Patients can fulfill
the CASPAR criteria to be diagnosed with PsA and dermatologists
may find these criteria useful when evaluating patients for pos-
sible signs of PsA (55). These classification criteria consist of two
groupings: the stem (or required criteria) and criteria associated
with a numerical value (54,55). To fulfill the CASPAR criteria, a
patient must present with at least one of the stem components
and 3 points from the criteria listed in Table 3.
The stem criteria of CASPAR are defined under the broad term
‘inflammatory articular disease,’ which consists of inflammatory
joint (peripheral) disease, enthesitis, and inflammatory axial dis-
ease. Inflammatory joint disease is generally recognized by joint
swelling, erythema, and pain (even at rest) (55).
As part of the clinical examination for peripheral arthritis (part
of the stem criteria of CASPAR), dermatologists should evaluate
patients for signs of swelling, which is indicative of active syno-
vitis, and tenderness, which is another sign of inflammation.
Practical assessments can be conducted by applying light pres-
sure (e.g. enough to blanch the tip of a fingernail) at the joint
line. Key joints to evaluate include DIP joints, proximal interpha-
langeal joints, metacarpophalangeal and metatarsophalangeal
joints, and wrist, elbow, shoulder, sternoclavicular, temporoman-
dibular, hip, knee, ankle, and midtarsal joints (56). Novel educa-
tional tools are being developed to help train dermatologists on
how to accurately perform a musculoskeletal examination to
screen for PsA.
Axial inflammatory articular disease (part of the stem criteria
of CASPAR) is typically characterized by slow-developing back
pain persisting for >3 months before age 40 years, alternating
buttock pain (caused by sacroiliitis), pain causing waking from
sleep during the second half of the night and prolonged morning
stiffness or stiffness upon immobility (57,58). Additionally,
treatments that are effective for other PsA domains may not
improve axial disease.
The numerically valued criteria of CASPAR include psoriasis or
a personal/family history of psoriasis, psoriatic nail dystrophy, a
negative test result for the presence of rheumatoid factor (RF),
current dactylitis or history of dactylitis (recorded by a rheuma-
tologist), and juxta-articular new-bone formation (54).
Among the CASPAR criteria, ongoing psoriasis (which is
weighted more than all other criteria) or a personal or family his-
tory of psoriasis is encompassed within one category, whereas
nail dystrophy is counted as a separate category. Of the remain-
ing criteria, dactylitis requires the most careful clinical attention,
because it may occur in any digit, but most frequently manifests
in the toes (59). A dactylitic digit, which is very specific to PsA,
may be red, hot, and tender (acute dactylitis) or swollen without
acute inflammatory changes (chronic dactylitis) and may occur in
isolation or as one of several digits affected (6,59,60). During clin-
ical examinations, dermatologists can identify dactylitis by screen-
ing for ‘sausage-shaped’ digits, which present with uniform
inflammation such that soft tissue between the metacarpophalan-
geal and proximal interphalangeal, proximal and DIP, and/or DIP
and digital tuft are diffusely swollen (61). The entire digit is
affected and swelling at each joint cannot be independently rec-
ognized, and flexion is difficult or impossible (62). The presence
of RF, a type of autoantibody first found to be associated with RA
and not typically present in PsA, is determined through a blood
test (63). Although negative RF is one of the numerically valued
CASPAR criteria, RF is present in approximately 13% of patients
with PsA, and the incidence of positive RF increases with age
(21,64). Anti-cyclic citrullinated peptide antibodies are an add-
itional negative marker of PsA (not included in the CASPAR crite-
ria); however, roughly 13% of patients with PsA present with
these antibodies (65). When positive in patients with PsA, both RF
and anti-cyclic citrullinated peptide antibodies typically have a
 JOURNAL OF DERMATOLOGICAL TREATMENT 665

Table 3. CASPAR criteria.

1:5 to 1:10

Female-to-
male ratio
3:1 to 4:1

1:1 to 2:1
Presence of inflammatory articular disease (joint, spine, or entheseal) with  3
points from the list below (54)

9:1

1:1
Characteristics (points)
Psoriasis (2) or Personal history of psoriasis (1) or Family history of

secondary to tophi eruption, eye

involvement, and manifestations
psoriasis (1)

Rarely: dermatologic manifestation

mimicking a tumor or infection

Extra-articular manifestations

Myalgias, tender points, irritable

Dactylitis or a history of dactylitis recorded by a rheumatologist (1)

Psoriasis, dactylitis, tendonitis,

Subcutaneous nodules, carpal

Juxta-articular new bone formation (1)

Negative for the rheumatoid factor (1)
Psoriatic nail dystrophy (1)

onychodystrophy
tunnel syndrome

bowel syndrome

Extensor tendon
None

Superficial &
deep laminae
Nail
90% ACPAþ

13% ACPAþ
75–80% RFþ
Laboratory

and ACPA

and ACPA

and ACPA
findings

Normal RF

Normal RF

Normal RF
13% RFþ
bone growth, enthesitis
Key radiographic findings

sclerosis, osteophytosis
Bone erosion, soft tissue
swelling, joint space
narrowing, marginal

Bone erosion and new

Joint space narrowing,

Deep lamina
Tophi, bone erosion

Flexor tendon

Figure 2. The fascia of the nail root is an extension of the entheses. Image from
McGonagle 2009 (179).
erosions

low titer, especially in comparison to patients with RA (66,67).

None

Finally, the last numerically valued CASPAR criteria, juxta-articular

new bone formation, is not typically a feature of early PsA.
involvement

Cervical and

Yes and no
lumbar

ACPA, anti-citrullinated peptide antibodies; PsA, psoriatic arthritis; RA, rheumatoid arthritis; RF, rheumatoid factor.
Axial

Atypical
Cervical

Psoriasis subtypes and PsA

Yes

Although psoriasis can occur in a variety of locations on the

Symmetrical

body, specific manifestations are clinical predictors of PsA (68).

Several studies have found an increased risk of PsA has correla-
Variably

Variably

tions with psoriatic scalp lesions, intertriginous/inverse psoriasis,

Yes

Yes

No

and nail dystrophy (68–71). The hazard ratios for PsA in patients
with scalp, intergluteal/perianal, and nail psoriasis are 3.89, 2.35,
Classically metatarsophalangeal/podagra

and 2.93, respectively (68), and in mild psoriasis, 83% of patients

Lower extremity, proximal and distal
Pattern of joint involvement

with scalp and nail psoriasis, 40% of patients with intergluteal/

Increased risk in patients with
may involve joints of any size

concurrent psoriasis and PSA

perianal lesions, and 37% of patients with isolated scalp psoriasis

interphalangeal joints, first

met CASPAR criteria for PsA (69). Similarly, the incidences of scalp,
carpometacarpal joint

intergluteal, and nail psoriasis were higher in patients with PsA

Small and large joints

(100, 83, and 64%, respectively) than in patients with psoriasis

alone (67, 25, and 40%, respectively) (70). Recognition of inverse
Large and small

psoriasis is an important clue for informing a diagnosis of PsA

that is commonly missed during physical examination. Inverse
Reproduced with modification from Mies Richie (150).
Diffuse

psoriasis has typically been considered uncommon but contem-

porary findings report a prevalence of 21–30% for inverse psoria-
sis in patients with psoriasis (72).
Inflammation

Although nail psoriasis is common in moderate-to-severe psor-

Table 2. Differential diagnosis of PsA.

iasis without PsA, it is even more prevalent in PsA (over 80% of

patients affected) and is hypothesized to indicate involvement of
Yes

Yes

Yes
No

No

the distal phalanx in PsA (55,68,73). This unique link between nail

In premenopausal women.

dystrophy and PsA can be explained by the physiological relation-

or acute
Chronic

Chronic

Chronic

Chronic

Chronic

ship between nails and entheses. Histological studies have dem-

Both

onstrated that the extensor tendon, which is attached to the

terminal phalanx, extends distally and connects with the nail root,
(43,148,149)
Osteoarthritis

Fibromyalgia

revealing that the fascia of the nail root is an extension of the

PsA (64,65)

enthesis and providing evidence of how inflammation of these

RA (145)

(146)

(147)
Disease

entheses often gives rise to nail pitting (Figure 2) (74). The link
Gout

between nail disease and adjacent enthesitis has further been

666 A. GOTTLIEB AND J. F. MEROLA
demonstrated through magnetic resonance imaging (MRI) and
ultrasound studies (75,76). Therefore, although nails are develop-
mentally related to the skin, they are functionally linked with
entheses, underscoring the correlation between nail disease/oste-
olysis and PsA – particularly in DIP joints (77,78).
Overall, these observations indicate that dermatologists should
pay particular attention for PsA manifestations in patients with
psoriasis affecting the scalp, intergluteal/perianal areas, and
nails (79).
Treatment of PsA
The European League Against Rheumatism (EULAR) and the
Group for Research and Assessment of Psoriasis and Psoriatic
Arthritis (GRAPPA) have developed recommendations for the
treatment of PsA, with guidelines for appropriate use of
nonsteroidal anti-inflammatory drugs (NSAIDs), traditional disease-
modifying anti-rheumatic drugs (DMARDs; e.g. methotrexate,
sulfasalazine, leflunomide, cyclosporine), biologics, and small-mol-
ecule inhibitors (80,81). These recommendations provide specific
guidance for treatment by PsA clinical domain. Choice of therapy
should be optimized to target the PsA symptoms that are the
most burdensome to each patient, with the overarching goals of
maximizing long-term health-related quality of life and preventing
irreversible joint structural damage (80,81). Briefly, NSAIDs are
recommended to control pain and inflammation in patients with
peripheral arthritis, axial disease, and enthesitis, and traditional
DMARDs are recommended as treatments for peripheral arthritis,
dactylitis, and skin/nail disease. Guidelines clarify that the term
‘DMARD’ to describe these agents was chosen for historical
purposes and that these agents do not provide any disease-modi-
fying effects on radiographic damage. Biologics that inhibit TNF-a,
IL-17A, or IL-12/23 are recommended across all PsA domains, and
the small-molecule phosphodiesterase-4 inhibitor, apremilast, is
recommended for all domains except axial disease (80,81). These
guidelines were developed in 2015, when data were available for
the TNF-a inhibitors, etanercept, adalimumab, infliximab, certolizu-
mab pegol, and golimumab, and for the IL-12/23 inhibitor, usteki-
numab (80,81). Since then, additional data have been published
for apremilast, the IL-17A inhibitors secukinumab and ixekizumab,
the Janus kinase inhibitor tofacitinib, and the T-cell inhibitor
abatacept, all of which are now approved for adults with active
PsA. The IL-23 inhibitor guselkumab is approved for moderate-to-
severe plaque psoriasis and is in late-stage development for PsA.
Additionally, NSAIDs, adalimumab, certolizumab pegol, etanercept,
golimumab, infliximab, and secukinumab are approved for the
treatment of ankylosing spondylitis (AS), a condition related
to PsA.
Domain-specific evaluation of PsA in clinical trials
Dermatologists should be particularly aware of measures used to
assess PsA, as the International Dermatology Outcome Measures
(IDEOM) group has recently encouraged screening and subse-
quent measurement of PsA symptoms in all psoriasis clinical trials
(82). The IDEOM group evaluated the patient global (PG)-arthritis,
routine assessment patient index data (RAPID)-3, and Psoriatic
Arthritis Impact of Disease (PsAID)-9 tools for PsA symptom evalu-
ation and recommended that PsAID9 and RAPID3 are potentially
more appropriate measures of PsA symptoms than PG-arthritis
(82). In PsA clinical trials, various measures (Table 4) are used to
assess peripheral arthritis, dactylitis, enthesitis, skin/nail disease,
and radiographic outcomes. Additionally, several different
instruments are used to evaluate patient health status (patient-
reported outcomes [PROs]), and several individual clinical and
PRO measures have been integrated into composite indices to
create more comprehensive measures.
Peripheral arthritis measures
Peripheral arthritis is predominantly assessed by indices, including
the 68 tender and 66 swollen joint count, the 28-joint Disease
Activity Score (DAS28), a composite measure that assesses 28
peripheral joints along with a measure of ESR or CRP (in the
DAS28-CRP measure), and the American College of Rheumatology
(ACR) criteria, another composite measure that specifies a
percentage improvement (i.e. 20, 50, or 70%) in tender or swollen
joint counts, as well as 3 of 5 additional measures (Table 4)
(56,83). These measures include the patient’s assessment of pain,
the patient’s global assessment of disease activity, the physician’s
assessment of physical function, the patient’s assessment of
physical function, and acute-phase reactant value. Furthermore,
when trials last longer than 1 year and agents are being tested as
DMARDs, ACR includes radiography or another imaging technique
(83,84). Across PsA clinical trials, 20% improvement in ACR criteria
(ACR20) has been used as a primary endpoint to assess the
efficacy of biologics and small-molecule inhibitors for the
treatment of articular symptoms. Results from these trials are
summarized in Figure 3. However, because DAS28 was originally
developed for RA, it does not evaluate some of the most
frequently involved joints in PsA (particularly in the lower
extremities) and all PsA domains. Although ACR response is used
as the primary endpoint in PsA clinical trials, it is not employed in
clinical practice and does not evaluate all PsA domains.
Dactylitis measures
Dactylitis is also measured using multiple approaches (Table 4).
The simplest assessment is counting dactylitic digits (tender and
non-tender or just tender) (85). Alternative clinical indices include
a 0–3 scale of physician-rated severity to assess all 20 digits (86),
the Leeds Dactylitis Index (LDI), and LDI-Basic (87,88). The LDI and
LDI-Basic multiply the tenderness score of each affected digit
(based on the Ritchie index – graded 0–3 for LDI or binary score
for LDI-Basic) by the ratio of the circumference of the affected
digit to the circumference of the digit on the opposite hand or
foot. Results from clinical trials using these indices to evaluate the
effects of treatment on dactylitis are summarized in Table 5.
Drugs that have shown statistically significant improvements in
dactylitis indices compared with placebo include infliximab,
certolizumab pegol, intravenous golimumab, subcutaneous
golimumab 100 mg, ustekinumab, guselkumab, secukinumab, and
ixekizumab. Statistical significance was not reached or was not
tested for in trials of adalimumab, etanercept, tofacitinib,
apremilast, and abatacept. It is not possible to indirectly compare
results across trials because different clinical indices and different
reporting methods were used to assess dactylitis across studies.
At present, there is no consensus on the best method for
assessing dactylitis in PsA clinical trials, and minimal clinically
important difference (MCID) thresholds have not been established
for available dactylitis indices.
Enthesitis measures
Enthesitis can be measured with imaging techniques, such as
ultrasound and MRI; however, in dermatology clinics, use of
 JOURNAL OF DERMATOLOGICAL TREATMENT 667

Table 4. Indices used to measure PsA activity by clinical domain (56,89,96–99,121,151–158).

PsA domain Measure Description/guidance for practical use Advantages/disadvantages
Peripheral arthritis 66 SJC, 68 TJC Specific joints are palpated for signs of tenderness and  Easy to perform; simple scoring
swelling, which are signs of inflammation and active  Can be completed in 2 min
synovitis. To perform, apply 4 kg/cm2 of pressure at  Good responsiveness in PsA clinical trials
the joint line  Severity of tenderness and swelling is
not graded
DAS28 A composite joint count measure that includes joints of  Good performance characteristics in PsA
both shoulders, elbows, knees, and wrists, as well as  Not recommended for use in PsA inclusion
all MCP joints, and all PIP joints of the hands criteria or as a primary endpoint in clinical
trials because it may underestimate disease
in lower extremities and DIP joints
 Severity of tenderness and swelling is
not graded
 Does not evaluate foot involvement, which
is common in PsA
ACR The ACR joint count documents the number of joints  Reliable measure of peripheral disease activ-
with tenderness and swelling ity in PsA clinical trials
 Can be used for patient follow-up in clin-
ical practice
Dactylitis 0–3 score assigned to Overall scores range from 0 (none) to 60 (severe)  Simple counting and scoring method
each digit of the  Demonstrated responsiveness in PsA trials
hands and feet of biologics
 Not as quantitative as LDI
LDI Uses an instrument called a dactylometer to measure  Minimal burden for patients
digit circumference and evaluate pain and tenderness  Objective quantitative measure
on a 0–3 scale; size comparisons are made vs. contra-  Requires a specialized tool (dactylometer)
lateral digits  More complicated scoring system that
involves comparison of the ratio of circum-
ferences between affected and contralat-
eral digits
Enthesitis 4-point enthesitis Enthesitis at Achilles tendon and plantar fascia graded  Demonstrated responsiveness in PsA clin-
measure as present or absent or scored on a 0–3 scale ical trials
 Does not perform as well as indices that
evaluate more sites
LEI Bilateral evaluation of six entheseal sites (lateral epicon-  Developed specifically for PsA
dyles, medial femoral condyles, and Achilles tendon  Can be completed in 30 s
insertions) for the presence (1) or absence (0)  Correlates well with other PsA disease activ-
of tenderness ity measures
 Least floor effect of available enthesi-
tis indices
MASES Evaluation of 13 entheseal sites (bilateral first costo-  Recommended by ASAS for use in SpA
chondral joints, seventh costochondral joints, poster- randomized controlled trials
ior superior iliac spines, anterior superior iliac spines,  Can be completed in 2–5 min
iliac crests, proximal insertion of Achilles tendons,  Demonstrated responsiveness in PsA clin-
and fifth lumbar spinous process) for the presence ical trials
(1) or absence (0) of tenderness  Not validated in PsA
 Lower ICC in patients with PsA vs. AS
SPARCC Bilateral evaluation of 16 entheseal sites (Achilles ten-  Can be completed in 2–5 min
dons, plantar fascia insertion at the calcaneus, patel-  Correlates well with AS disease activ-
lar tendon insertion at base of the patella, quadriceps ity measures
insertion into the superior border of the patella,  Not validated in PsA
supraspinatus insertion into the greater tuberosity of
the humerus, and medial and lateral epicondyles) for
the presence (1) or absence (0) of tenderness.
Modified versions are available evaluating 6 and
8 sites
Berlin Evaluation of 12 entheseal sites scored as absent (0) or  Has not been used in PsA clinical trials
present (1)  Lower ICC in patients with PsA vs. AS
San Francisco Evaluation of 17 tendon-insertion sites scored based on  More sensitive than Berlin index and MASES
pain and tenderness on a scale of 0–3 in AS clinical trial
 Has not been used in PsA clinical trials
 Lower ICC in patients with PsA vs. AS
Skin PASI Quantitative assessment of skin lesions based on BSA  Widely used in psoriasis and PsA clin-
affected and severity of erythema, induration, and ical trials
scale, weighted by body area  Can be administered in 5 min
 Not used in clinical practice, in part because
of complexity
PGA Assessment of skin lesions scored on a scale from 0  Simpler to use than PASI
(clear) to 6 (very severe)  Widely recognized and accepted by
dermatologists
 Less quantitative than PASI
BSA Assessed by considering the surface area of skin  Basic, easy-to-perform assessment that can
affected by psoriasis lesions; patient’s handprint be used in daily practice
(palm and fingers) is estimated to be 1% BSA  Does not include assessment of lesion sever-
ity or body location affected
(continued)
668 A. GOTTLIEB AND J. F. MEROLA

Table 4. Continued.
PsA domain Measure Description/guidance for practical use
Nails NAPSI Nails are scored based on the presence or absence of
nail bed and nail matrix psoriasis, with each nail div-
ided into four quadrants (scores for each nail range
from 0 to 8)
Modified NAPSI Each nail is evaluated for seven features: pitting, ony-
cholysis and oil-dropping dyschromia, nail plate
crumbling, leukonychia, splinter hemorrhages, hyper-
keratosis, and red spots in the lunula
Radiographic Modified Steinbrocker 40 joints in the hands and feet are classified on a 0–4
progression global scoring radiographic scale in which 0 ¼ normal, 1 ¼ juxta-
method articular osteoporosis or soft-tissue swelling, 2 ¼ ero-
sions, 3 ¼ erosion and joint-space narrowing or sub-
luxation, and 4 ¼ total joint destruction (lysis
or ankylosis)
Sharp method Evaluates joints in the hands (40–44 joints) and feet
for PsA (8–12 joints) for erosions and joint-space narrowing
on a scale of 0–5; separate grading is used for pen-
cil-in-cup phenomenon, gross osteolysis, periostitis,
and tuft resorption
Sharp/van der Heijde Erosions are scored from 0 to 5 and joint-space narrow-
method for PsA ing from 0 to 4, with pencil-in-cup and osteolysis
scored separately
PARS Assessment of 40 joints in the hands and feet scored
separately for destruction (0–5 scale) and bony prolif-
eration (0–4 scale) for a total score range of 0–360
Spine BASDAI Set of 6 questionnaires scored on a 0–10 cm VAS about
assessment symptoms of fatigue, pain, and stiffness
BASFI Set of 10 items related to functional anatomy (bending,
reaching, changing position, standing, turning, and
climbing steps) and ability to cope with everyday life
rated on a 0–10 cm VAS
ACR: American College of Rheumatology; AS: ankylosing spondylitis; ASAS: Assessment of SpondyloArthritis international Society; BASDAI: Bath Ankylosing
Spondylitis Disease Activity Index; BASFI: Bath Ankylosing Spondylitis Function Index; BSA: body surface area; DAS28: Disease Activity Score in 28 joints; DIP: distal
interphalangeal; ICC: intraclass correlation coefficient; LDI: Leeds Dactylitis Index; LEI: Leeds Enthesitis Index; MASES: Maastricht Ankylosing Spondylitis Enthesitis
Score; MCID: minimal clinically important difference; MCP: metacarpophalangeal; NA: not available; NAPSI: nail psoriasis severity index; PARS: Psoriatic Arthritis
Ratingen score; PASI: psoriasis area and severity index; PGA: physician global assessment; PIP: proximal interphalangeal; PsA: psoriatic arthritis; RA: rheumatoid arth-
ritis; SDD: smallest detectable difference; SJC: swollen joint count; SpA: spondyloarthritis; SPARCC: spondyloarthritis research consortium of Canada; TJC: tender joint
count; VAS: visual analog scale.
Advantages/disadvantages
 Has been used extensively in psoriasis clin-
ical trials
 Relatively straightforward physical
examination
 Can be completed in 5–10 min
 Not validated in psoriasis or PsA
 Not used in clinical practice
 Shorter and easier to use than NAPSI
 Good inter-rater reliability
 Used in PsA clinical trials
 Well correlated with other clinical measures
of PsA
 Relatively straightforward physical
examination
 Can be completed in <5 min
 Simple scoring method used since 1949
 Can be performed quickly in clinical prac-
tice (6 min)
 Does not include use of any radio-
graphic standards
 Less sensitive than other methods
 Various Sharp score modifications have been
used in different PsA clinical trials
 More sensitive to detecting change in RA
than PsA
 Time-consuming and not practical for use in
a clinical setting
 Has been widely used in PsA clinical trials
 Can be performed in 15 min
 Changes > MCID have not been observed in
PsA clinical trials because disease progres-
sion is slow relative to study durations
 Validated in PsA
 Only instrument to evaluate proliferation,
which is a PsA-specific feature
 Can be performed in 10 min
 Destruction and proliferation scales are only
weakly correlated
 Has not been used in any clinical trials
 Most commonly used measure in AS clin-
ical trials
 Can be completed in 2 min
 Does not discriminate well between periph-
eral and axial PsA disease activity
 Fails to discriminate between high and low
PsA disease activity
 Commonly used in AS disease
impact studies
 Can be completed in <3 min
 Does not discriminate well between periph-
eral and axial disease activity

domain-specific clinical indices is more practical. Instruments avail-
able for the assessment of enthesitis include the Leeds Enthesitis
Index (LEI), the Maastricht Ankylosing Spondylitis Enthesitis Score
(MASES), the 4-point enthesitis measure, the Spondyloarthritis
Research Consortium of Canada (SPARCC) enthesitis measure, the
Berlin index, and the San Francisco index (Table 4) (56).
As with dactylitis, there is currently no consensus on which
enthesitis index is best; therefore, PsA trials of biologics and
small-molecule inhibitors have used different instruments. As
shown in Table 6, even when the same instrument was used in
different studies, differences in reporting methods and study
designs restrict the ability to indirectly compare results across
studies. Furthermore, the clinical significance of improvements on
different indices is not well established, and MCID is not available
for any enthesitis measure (89,90). However, it is noteworthy that
statistically significant improvements in enthesitis have been
reported compared with placebo in phase 3 studies of infliximab,
certolizumab pegol, golimumab (subcutaneous and intravenous
formulations), secukinumab, ustekinumab, and apremilast, and in
a phase 2 study of guselkumab (Table 6).
 JOURNAL OF DERMATOLOGICAL TREATMENT 669

100

76.8

% of patients achieving
80 71.7

ACR20 at Week 24
69
63.8 65
61 60
57 56.3 58
60 52 53 51
54
48 49 49.5
42.4
39.4
36.6
40
26.4

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Figure 3. ACR20 response rates reported at week 24 in PsA trials of biologics and small-molecule inhibitors (86,102,103,132,134–136,138,139,159–161,180). For agents
without a dose specified, results are presented for the approved dosage. Figure is for visualization purposes only and should not be used to make direct comparisons
of efficacy between therapies. Data values have not been statistically corrected. Unless otherwise indicated, the proportion of patients with ACR20 at week 24 was
the primary endpoint of the study. ACR: American College of Rheumatology; BID: two times daily; BIW: twice weekly; PsA: psoriatic arthritis; Q2W: every 2 weeks;
Q4W; every 4 weeks; QW: once weekly.
Primary endpoint: ACR20 at week 12; †Primary endpoint: ACR20 at week 16; ‡ACR20 at week 24 is a secondary endpoint;
§
Primary endpoint: ACR20 at week 14; ||Results reported at week 16 (primary endpoint).

Table 5. Results of dactylitis assessments by clinical index from trials of biologics and small-molecule inhibitors in PsA.
Dactylitis index Trial name/description
Scale of 0–3 for each ADEPT (Adalimumab Effectiveness in Psoriatic
digit of the hands Arthritis Trial) (159)
and feet PRESTA (Psoriasis Randomized Etanercept STudy in
Subjects with Psoriatic Arthritis) (160)
IMPACT (Infliximab Multinational Psoriatic Arthritis
Controlled Trial) (86)
GO-REVEAL (A Randomized Evaluation of Safety
and Efficacy in Subjects with Psoriatic Arthritis
Using a Human Anti-TNF Monoclonal
Antibody) (161)
GO-VIBRANT (A study of golimumab in participants
with active PsA) (102)
PSUMMIT 1 (A study of the safety and effectiveness
of ustekinumab in patients with PsA) (138)
OPAL Beyond (Oral Psoriatic Arthritis Trial;
Tofacitinib in PsA subjects with inadequate
response to TNF inhibitors) (134)
Efficacy and safety of guselkumab in patients with
active PsA: a phase 2a, randomized, double-
blind, placebo-controlled study (132)
Presence (1) or absence (0) FUTURE 1 (Efficacy at 24 weeks and long-term
for each digit of the safety, tolerability and efficacy up to 2 years of
hands and feet secukinumab (AIN457) in patients with active
PsA (133)
PALACE 1 (Psoriatic Arthritis Long-term Assessment
of Clinical Efficacy 1) (135)
LDI or LDI-Basic RAPID-PsA (Certolizumab pegol in subjects with
adult onset active and progressive PsA) (139)
SPIRIT-P1 (A study of ixekizumab in participants
with active PsA) (136)
ASTRAEA (Active PSoriaTic Arthritis RandomizEd
TriAl) (103)
BID: two times daily; IV: intravenous; LDI: Leeds Dactylitis Index; PsA: psoriatic arthritis; Q2W: every 2 weeks; Q4W: every 4 weeks; TNF: tumor necrosis factor.
Key dactylitis outcomes
Mean improvement in dactylitis was greater with adalimumab vs. placebo
but statistical significance was not reached (values not reported)
Mean percent change from baseline to week 24 was 85% with etanercept
50 mg BIW/QW and 85% with etanercept 50 mg QW/QW
At week 16, mean percent improvement was 85% in the infliximab group
vs. 29% in the placebo group (p < .001)
Median percent change from baseline to week 24 was 100% with
golimumab 50 mg, 100% with golimumab 100 mg, and 42% with
placebo (both p  .09 vs. placebo)
Mean change from baseline to week 24 in dactylitis score was –8.2 with IV
golimumab 2 mg/kg and –5.0 with placebo (p < .001)
Among patients with dactylitis at baseline, dactylitis was present at week
24 in 56% of patients treated with ustekinumab 45 or 90 mg vs. 76% of
the placebo group (p¼.0013)
Mean dactylitis score change from baseline to month 3 was –5.2 with
tofacitinib 5 mg, –5.4 with tofacitinib 10 mg, and –1.9 with placebo
(statistical significance not tested)
Median percent improvement from baseline to week 24 was 100% with
guselkumab 100 mg and 33% with placebo (p < .001)
At week 24, complete resolution of dactylitis was achieved by 52% of
patients receiving secukinumab 75 or 150 mg compared with 16% of
the placebo group (p < .05)
The percentage of patients with complete resolution of dactylitis at week
24 was 51% with apremilast 20 mg BID, 48% with apremilast 30 mg
BID, and 41% with placebo (statistical significance not reached)
Mean LDI change at week 24 was –40.7 with certolizumab pegol 200 mg
Q2W, –53.5 with certolizumab pegol 400 mg Q4W, and –22.0 with pla-
cebo (both p  .002)
Mean change from baseline in LDI-Basic was –75.4 with ixekizumab Q4W,
–66.1 with ixekizumab Q2W, and –33.7 with placebo (both p < .05 vs.
placebo). Complete resolution of dactylitis (LDI-Basic score ¼ 0) was
reported by 80% of the ixekizumab Q4W group, 77% in the ixekizumab
Q2W group, and 25% of the placebo group (both p  .001 vs. placebo)
Using LDI-Basic, complete resolution of dactylitis at week 24 was achieved
by 44% of patients treated with abatacept vs. 34% with placebo; statis-
tical significance was not reached
670 A. GOTTLIEB AND J. F. MEROLA
Table 6. Results of enthesitis assessments by clinical index from trials of biologics and small-molecule inhibitors in PsA.
Enthesitis index Trial name/description
4-point scale ADEPT (Adalimumab Effectiveness in Psoriatic Arthritis
Trial) (159)
PRESTA (Psoriasis Randomized Etanercept STudy in
Subjects with Psoriatic Arthritis) (160)
IMPACT (Infliximab Multinational Psoriatic Arthritis
Controlled Trial) (86)
FUTURE 1 (Efficacy at 24 weeks and long term safety,
tolerability and efficacy up to 2 years of
secukinumab (AIN457) in patients with active
PsA (133)
LEI RAPID-PsA (Certolizumab pegol in subjects with adult
onset active and progressive PsA) (139)
GO-VIBRANT (A study of golimumab in participants
with active PsA) (102)
SPIRIT-P1 (A study of ixekizumab in participants with
active PsA) (136)
OPAL Beyond (Oral Psoriatic Arthritis Trial; Tofacitinib
in PsA subjects with inadequate response to TNF
inhibitors) (134)
ASTRAEA (Active PSoriaTic Arthritis RandomizEd
TriAl) (103)
Efficacy and safety of guselkumab in patients with
active PsA: a phase 2a, randomized, double-blind,
placebo-controlled study (132)
MASES or modified GO-REVEAL (A Randomized Evaluation of Safety and
MASES Efficacy in Subjects with Psoriatic Arthritis Using a
Human Anti-TNF Monoclonal Antibody) (161)
PSUMMIT 1 (A study of the safety and effectiveness of
ustekinumab in patients with PsA) (138)
PALACE 1 (Psoriatic Arthritis Long-term Assessment of
Clinical Efficacy 1) (135)
BID: two times daily; BIW: twice weekly; IV: intravenous; IXEQ2W: ixekizumab 80 mg once every 2 weeks; IXEQ4W: ixekizumab 80 mg once every 4 weeks; LEI: Leeds
Enthesitis Index; MASES: Maastricht Ankylosing Spondylitis Enthesitis Score; PsA: psoriatic arthritis; Q2W: every 2 weeks; Q4W: every 4 weeks; QW: once weekly; TNF:
tumor necrosis factor.
Skin and nail psoriasis measures
Psoriasis is measured by tools frequently used in dermatology
trials, including the psoriasis area and severity index (PASI),
body surface area (BSA), physicians global assessment (PGA),
Investigator’s Global Assessment (IGA), or IGA modified 2011
(Table 4) (56,91). The primary endpoint in psoriasis trials and the
key skin endpoint in PsA trials are PASI responses (usually
percentage of patients achieving at least 75% improvement in
PASI scores [PASI75]). Nail psoriasis is assessed using the nail
psoriasis severity index (NAPSI) or modified NAPSI (Table 4) (56).
The National Psoriasis Foundation recently defined
acceptable response as either BSA 3% or 75% BSA
improvement from baseline and target response as BSA
1% for patients with psoriasis (92). Additionally, the
product of PGA and BSA (PGAxBSA) is a simple tool for
assessing psoriasis severity and response to treatment with
concordance to PASI response that can evaluate treatment
targets for psoriasis (93–95). As use of newer biologics and
small-molecule inhibitors will be needed to meet these
goals, it is critical that dermatologists understand the
impact that these drugs have on PsA and other domains of
psoriatic disease so that patients are appropriately treated.
Treatment of skin disease by dermatologists is an import-
ant component of comprehensive PsA disease management.
Key enthesitis outcomes
Mean improvement in enthesitis was greater with adalimumab vs placebo,
but statistical significance was not reached (values not reported)
81% of patients treated with etanercept 50 mg BIW/QW, and 81% of patients
treated with etanercept 50 mg QW/QW had a reduction in enthesitis sites
at week 24
At week 16, 14% of patients treated with infliximab compared with 31% of
the placebo group had enthesitis (p < .001)
At week 24, complete resolution of enthesitis was achieved by 48% of
patients treated with secukinumab 75 or 150 mg compared with 13% of
the placebo group (p < .05)
In patients with LEI >1 at baseline, mean change at week 24 was –2.0 with
certolizumab pegol 200 mg Q2W, –1.8 with certolizumab pegol 400 mg
Q4W, and –1.1 with placebo (both p  .003)
Mean change from baseline to week 14 in LEI was –2.1 with IV golimumab
2 mg/kg and –1.1 with placebo (p < .001)
Mean LEI score change from baseline to week 24 was 1.3 for IXEQ4W, 1.4
for IXEQ2W, and 0.8 for placebo (statistical significance not reached)
Mean LEI score change from baseline to month 3 was –1.3 with tofacitinib
5 mg, –1.3 with tofacitinib 10 mg, –0.5 with placebo (statistical significance
not tested)
Complete resolution of enthesitis at week 24 was achieved by 33% of
patients treated with abatacept vs. 21% with placebo (statistical signifi-
cance not reached)
Median percent improvement from baseline to week 24 was 100% with
guselkumab 100 mg and 33% with placebo (p ¼ .009)
Median percent change on modified MASES from baseline to week 24 was
60% with golimumab 50 mg, 67% with golimumab 100 mg, and 12% with
placebo (both p < .001 vs. placebo)
Among patients with modified MASES 1 at baseline, enthesitis was present
at week 24 in 65% of patients treated with ustekinumab 45 or 90 mg vs.
81% of the placebo group (p ¼ .0006)
The percentage of patients with complete resolution of enthesitis at week 24
was 32% with apremilast 20 mg BID, 34% with apremilast 30 mg BID, and
14% with placebo; both p  .0037 vs. placebo
While PsA clinical trials have included skin assessments,
results from psoriasis trials can provide the most specific
and focused information on the effects of different therapies
on clearance of skin and nail lesions. Table 7 summarizes
PASI and NAPSI response rates for biologic and small-mol-
ecule inhibitor therapies approved for the treatment of
moderate-to-severe plaque psoriasis, including etanercept,
infliximab, adalimumab, ustekinumab, guselkumab,
secukinumab, ixekizumab, and apremilast.
Radiographic measures
As shown in Table 4, the most common radiographic scoring
methods for PsA clinical trials are modified from RA scoring meth-
ods and include the modified Steinbrocker, the modified Sharp
method for PsA, the modified Sharp/van der Heijde method for
PsA (also reported as the van der Heijde-modified total Sharp
score [mTSS]), and the Psoriatic Arthritis Ratingen Score (PARS)
(96). Although these tools all analyze joints in the hands and feet,
scoring criteria vary between methods. For example, both
modified Sharp and mTSS separately assess erosions and joint
space narrowing (a product of cartilage destruction), whereas the
PARS method separately assesses erosions and bony prolifera-
tions. Further, the modified Steinbrocker uses only one scale that
considers erosions, joint space narrowing, and ankylosis. GRAPPA

Table 7. Results of psoriasis assessments from trials of biologics and small-molecule inhibitors in chronic plaque psoriasis.
Skin outcomes
Drug Trial
Etanercept Etanercept as monotherapy
in patients with psoria-
sis (162)
Infliximab EXPRESS (Infliximab induction
and maintenance therapy
for moderate-to-severe
psoriasis) (164)
Adalimumab REVEAL (Adalimumab therapy
for moderate to severe
psoriasis) (165)
Ustekinumab PHOENIX 1 (Efficacy and
safety of ustekinumab in
patients with psoria-
sis) (167)
Secukinumab ERASURE (Efficacy or
response and safety of
two fixed secukinumab
regimens in psoria-
sis) (169)
Ixekizumab UNCOVER-3 (Comparison of
ixekizumab with
etanercept or placebo in
moderate-to-severe
psoriasis) (171)
Apremilast ESTEEM 1 (Efficacy and safety
trial evaluating the effects
of apremilast in psoria-
sis) (173)
JOURNAL OF DERMATOLOGICAL TREATMENT 671
Nail outcomes
PASI result Trial NAPSI result
Week 12 PASI 75 Open-label trial of the effects Mean target fingernail NAPSI
 49% with 50 mg BIW (p < .001 of etanercept 50 mg BIW/ score change from baseline
vs. placebo) QW or QW/QW on nail to week 24:
 34% with 25 mg BIW (p < .001 psoriasis in patients with  –4.3 with etanercept
vs. placebo) moderate-to-severe plaque 50 mg BIW/QW
 14% with 25 mg QW (p < .001 psoriasis (163)  –4.4 with etanercept
vs. placebo) 100 mg QW/QW
 4% with placebo
Week 12 PASI 90
 22% with 50 mg BIW (p < .001
vs. placebo)
 12% with 25 mg BIW (p < .001
vs. placebo)
 3% with 25 mg QW
 1% with placebo
Week 10 EXPRESS (164) NAPSI % improvement from
 PASI 75 achieved by 80% with baseline to week 24:
infliximab vs. 3% with pla-  56% with infliximab vs.
cebo (p < .0001) –3% with pla-
 PASI 90 achieved by 57% with cebo (p < .0001)
infliximab vs. 1% with pla-
cebo (p < .0001)
Week 12 Post hoc nail psoriasis suba- Median NAPSI response at
 PASI 75 achieved by 68% with nalysis of data from the week 16, 40%
adalimumab vs. 5% with pla- BELIEVE study in patients
cebo (p < .001 vs. placebo) with moderate-to-severe
 PASI 90 achieved by 37% with psoriasis (166)
adalimumab vs. 2% with pla-
cebo (p < .001 vs. placebo)
Week 12 PASI 75 PHOENIX 1 (168) NAPSI % improvement from
 66% with ustekinumab 90 mg baseline to week 24:
(p < .0001 vs. placebo)  47% with ustekinu-
 67% with ustekinumab 45 mg mab 45 mg
(p < .0001 vs. placebo)  49% with ustekinu-
 Placebo 3% mab 90 mg
Week 12 PASI 90
 37% with ustekinumab 90 mg
(p < .0001 vs. placebo)
 42% with ustekinumab 45 mg
(p < .0001 vs. placebo)
 Placebo 2%
Week 12 PASI 75 TRANSFIGURE (Phase 3b Mean NAPSI % change from
 82% with secukinumab study of secukinumab vs. baseline to week 16:
300 mg (p < .001 vs. placebo) placebo in patients with  –45% with secukinumab
 72% with secukinumab moderate-to-severe psoria- 300 mg (p < .0001
150 mg (p < .001 vs. placebo) sis with nail involve- vs. placebo)
 5% with placebo ment (170)  –38% with secukinumab
Week 12 PASI 90 150 mg (p < .0001
 59% with secukinumab vs. placebo)
300 mg (p < .001 vs. placebo)  –11% with placebo
 39% with secukinumab
150 mg (p < .001 vs. placebo)
 1% with placebo
Week 12 PASI 75 UNCOVER-3 (172) Mean NAPSI % change from
 84% with ixekizumab Q4W baseline to week 12:
(p < .0001 vs. placebo)  –39% with
 87% with ixekizumab Q2W ixekizumab Q2W
(p < .0001 vs. placebo)  –40% with
 7% with placebo ixekizumab Q4W
Week 12 PASI 90  þ5% with placebo
 65% with ixekizumab Q4W
(p < .0001 vs. placebo)
 68% with ixekizumab Q2W
(p < .0001 vs. placebo)
 3% with placebo
Week 16 PASI 75 Subanalysis of ESTEEM 1 and Mean NAPSI % change vs pla-
 33% with apremilast 30 mg ESTEEM 2 data for apremi- cebo at week 16:
BID (p < .0001 vs. placebo) last 30 mg BID vs. placebo  –23% vs. þ6.5% in
 5% with placebo in patients with moderate- ESTEEM 1; p < .0001
to-severe psoriasis (174)  –29% vs. –7.1% in
ESTEEM 2; p < .0001
(continued)
672 A. GOTTLIEB AND J. F. MEROLA

Table 7. Continued.
Skin outcomes Nail outcomes
Drug Trial PASI result Trial NAPSI result
Guselkumab VOYAGE 1 (Efficacy and Week 16 PASI 75 VOYAGE 1 (175) Mean NAPSI % change from
safety of guselkumab com-  91% with guselkumab baseline to week 16:
pared with adalimumab (p < .001 vs. placebo)  34% with guselkumab
for the continuous treat-  6% with placebo  –1% with placebo
ment of patients with Week 16 PASI 90
moderate-to-severe psoria-  73% with guselkumab
sis (175) (p < .001 vs. placebo)
 3% with placebo
BIW: twice weekly; NAPSI: Nail Psoriasis Severity Index; PASI: Psoriasis Area and Severity Index; Q2W: every 2 weeks; Q4W: every 4 weeks; QW: once weekly.

Table 8. Results of radiographic progression assessments from trials of biologics and small-molecule inhibitors in PsA.
Trial name/description
Etanercept treatment of PsA: safety, efficacy, and effect on
disease progression (137)
ADEPT (Adalimumab Effectiveness in Psoriatic Arthritis
Trial (131)
FUTURE 5 (Study to Demonstrate the Efficacy [Including
Inhibition of Structural Damage], Safety and Tolerability up
to 2 Years of Secukinumab in Active Psoriatic
Arthritis) (176)
SPIRIT-P1 (A study of ixekizumab in participants with active
PsA) (136)
IMPACT 2 (Infliximab Multinational Psoriatic Arthritis
Controlled Trial 2) (100)
GO-REVEAL (A Randomized Evaluation of Safety and Efficacy
in Subjects with Psoriatic Arthritis Using a Human Anti-TNF
Monoclonal Antibody) (101)
GO-VIBRANT (A study of golimumab in participants with active
PsA) (102)
RAPID-PsA (Certolizumab pegol in subjects with adult onset
active and progressive PsA) (177)
PSUMMIT-1 and PSUMMIT-2 (Study of the safety and effective-
ness of ustekinumab in patients with PsA) (29)
ASTRAEA (Active PSoriaTic Arthritis RandomizEd TriAl) (103)
mTSS: modified total Sharp score; PsA: psoriatic arthritis; Q2W: every 2 weeks; Q4W: every 4 weeks; QW: once weekly; SDC: smallest detectable change; SHS: Sharp/
van der Heijde score; TSS: total Sharp score.
Key radiographic outcomes
Annualized rate of change in modified TSS at 12 months was –0.03 units with etanercept vs.
þ1.00 unit for placebo (p ¼ .0001)
At week 24, mean change from baseline in modified TSS was –0.1 with adalimumab and þ0.9
with placebo; changes at week 48 were þ0.1 and þ1.0, respectively (SDC ¼ 1.88)
At week 24, mean change from baseline in modified TSS was þ0.08 with secukinumab 300 mg
with loading dose (p < .01 vs. placebo), þ0.17 with secukinumab 150 mg with loading dose
(p < .05 vs. placebo), –0.09 with secukinumab 150 mg without loading dose (p < .05 vs. pla-
cebo), and þ0.50 with placebo
At week 24, mean change from baseline in modified TSS was þ0.17 with ixekizumab Q4W,
þ0.08 with ixekizumab Q2W, and þ0.49 with placebo (both p  .01)
On a 0–528 scale (SDC ¼ 2.7), mean PsA-modified SHS change from baseline to week 24 was
–0.70 with infliximab 5 mg and þ0.82 with placebo (p ¼ .001); 97% of the infliximab group
and 88% of the placebo group had scores  SDD
On a 0–528 scale (SDC ¼ 1.56), mean changes from baseline to week 24 on the PsA-modified
SHS were –0.16 with golimumab 50 mg (p ¼ .011 vs. placebo), –0.02 with golimumab 100 mg
(p ¼ .086 vs. placebo), and þ0.27 with placebo. The percent of patients with a PsA-modified
SHS change from baseline  SDD was 96% with golimumab 50 mg, 94% with golimumab
100 mg, and 89% with placebo
On a 0–528 scale (SDC ¼ 2.49), mean change in total PsA-modified SHS was –0.4 with intraven-
ous golimumab 2 mg/kg vs. 2.0 in the placebo group (p < .001)
Imputation method significantly affected assessment and reporting of radiographic progression
With no imputation, mTSS change from baseline to week 24 was þ0.06 with certolizumab
pegol (pooled doses) and þ 0.29 with placebo (p ¼ .008)
On a 0–528 scale (SDC ¼ 2.01), mean changes from baseline to week 24 was 0.4 with
ustekinumab 45 or 90 mg and 1.0 with placebo (p < .001). In both groups, change in SHS
was  SDD for most patients (92% with ustekinumab and 84% with placebo; p < .001)
Mean change from baseline in PsA-modified total SHS score was 0.30 with abatacept vs. 0.35
with placebo at week 24; statistical significance and SDC not reported

consensus is that the Sharp/van der Heijde method for PsA is the
optimal tool for use in randomized controlled trials (97).
Radiographic progression results from PsA trials are summar-
ized in Table 8. All drugs, except abatacept, were associated with
statistically significant differences compared with placebo in
mTSS/modified Sharp/van der Heijde score (not reported for
guselkumab, apremilast, or tofacitinib). However, differences
between active treatment and placebo were below the MCID
based on the smallest detectable difference observed in RA
studies (98,99). In many cases, most (>80%) patients in both
placebo and active-treatment groups had a change in Sharp/van
der Heijde score that was below the smallest detectable change,
indicating that no measurable progression was observed in the
majority of patients during the study period (29,100–102). This
lack of progression has made it difficult to detect meaningful
treatment differences in radiographic progression (103). Of the
drugs available for PsA, approval for inhibition of radiographic
progression is given for adalimumab, etanercept, certolizumab
pegol, infliximab, ixekizumab, secukinumab, and abatacept by
both the FDA and EMA (104–117). For golimumab, ustekinumab,
and tofacitinib, only the EMA gives approval for inhibition of
radiographic progression (118–120). Apremilast does not have
approval for inhibition of radiographic progression from
either agency.
Spine measures
The most commonly used indices for assessment of spondylitis
include the Bath Ankylosing Spondylitis Disease Activity Index
(BASDAI) and the Bath Ankylosing Spondylitis Functional Index
(BASFI) (Table 4). Components of the BASDAI and BASFI, along
with patient assessments of spinal pain and global impression of
disease activity rated on a 0–10 cm visual analog scale, are
included in the composite Assessment of SpondyloArthritis inter-
national Society (ASAS) improvement criteria (121), which is the
most common primary endpoint in recent AS clinical trials.
While axial disease is an important clinical domain of PsA,
fewer than 5% of patients have isolated spinal joint involvement
(26). Thus, because not all patients with PsA present with spinal
involvement and use of MRI in clinical trials is expensive, formal
assessment of spondylitis has not been performed in randomized
controlled PsA trials. However, the effects of biologic and small-

molecule inhibitor therapies on axial disease in PsA can be
inferred from results of controlled clinical trials of these agents in
patients with AS. All TNF-a inhibitors approved for the treatment
of active PsA (etanercept, adalimumab, infliximab, golimumab,
and certolizumab pegol) are also approved for the treatment of
AS. In AS clinical trials, ASAS20 response rates were similar to all
TNF-a inhibitors, ranging from 58 to 61% (122). In the MEASURE 1
and MEASURE 2 studies of the IL-17A inhibitor secukinumab in
patients with AS, ASAS20 response rates at week 16 were 61 and
61%, respectively, with the 150-mg dose and 60 and 41%,
respectively, with the 75-mg dose (123). ASAS20 response rates
were significantly higher with tofacitinib 5 mg (80.8%) compared
with placebo (41.2%; p < .001) in a phase 2 dose-ranging study in
AS (124). In a small open-label pilot study of abatacept in AS,
27% of TNF inhibitor-naïve and 20% of TNF inhibitor-experienced
patients achieved ASAS20 responses, suggesting limited efficacy
of abatacept for this indication (125). Methotrexate has not been
demonstrated to show benefit in patients with AS (126). A clinical
trial of ixekizumab (NCT02696798) is ongoing in AS.
PRO measures
PRO measures were developed to assess patients’ perspectives of
various quality-of-life domains. These measures include the pain
visual analog scale (VAS), the health assessment questionnaire
disability index (HAQ-DI), the EuroQoL 5 dimension questionnaire
(EQ-5D), and the 36-item short form survey (SF-36), which is bro-
ken into the physical component summary (PCS) and mental
component summary (MCS) (56). Changes from baseline of
10 mm for pain VAS and 0.30–0.35 for HAQ-DI have been
used as MCID in PsA trials, and an MCID for change from baseline
in SF-36 has been defined as 5–10 (2.5–5 for PCS and MCS
individually) in PsA (101,127–130). Clinically important improve-
ments in these PROs have been reported in PsA clinical trials of
adalimumab, etanercept, infliximab, golimumab (subcutaneous
and intravenous), certolizumab pegol, ustekinumab, guselkumab,
secukinumab, ixekizumab, apremilast, tofacitinib, and abatacept
(100–103,131–139). Additionally, the PsAID12, which is available
on the GRAPPA mobile-phone app, and the RAPID3 question-
naires are useful for dermatologists to use in clinical practice to
evaluate the impact of PsA symptoms on patients (140,141).
Additional composite measures
Composite indices, such as the Psoriatic Arthritis Disease Activity
Score (PASDAS), have been developed as a means of integrating
information from a variety of individual outcome indices, includ-
ing physician’s global assessment scores, disease activity indices,
and PROs into one meaningful measure of PsA (142). Minimal dis-
ease activity (MDA), a measure that encompasses all aspects of
PsA, is different from PASDAS and similar composite indices
because it was created to be an objective target for treatment.
When MDA criteria are met, PsA is considered to be in a satisfac-
tory state of disease activity for both patients and physicians.
Patients are classified as achieving MDA when they meet 5 of 7
criteria, including tender joint count 1; swollen joint count 1;
PASI 1 or body surface area 3%; patient pain VAS 15; patient
global disease activity VAS 20; health assessment questionnaire
0.5; and tender entheseal points 1 (143). The value of using
MDA as a treatment target was demonstrated in the TIght
COntrol of Psoriatic Arthritis (TICOPA) trial (144). In this study,
MDA was successfully used as an objective goal in a treat-to-tar-
get approach as patients with early PsA treated with this tight
JOURNAL OF DERMATOLOGICAL TREATMENT 673
control goal had significantly improved joint outcomes compared
with patients receiving standard care.
Summary
PsA is a heterogeneous, rapidly developing disease with poten-
tially deleterious effects and frequently occurs within 10 years fol-
lowing the appearance of psoriasis (21). We consider PsA to be
the major comorbidity of psoriasis due to the likelihood of PsA to
result in permanent disability if left untreated. Early PsA diagnosis
and initiation of treatment can prevent possibly adverse conse-
quences, whereas a diagnostic delay of more than 6 months con-
tributes to poor radiographic and functional outcomes (27).
Therefore, while providing important care to manage the skin
symptoms of psoriasis, dermatologists have the unique ability to
recognize early signs of PsA in patients with psoriasis and be the
first healthcare practitioners to detect PsA. Dermatologists can
then initiate treatment with agents that are effective for both
psoriasis and PsA. There are currently available PsA drugs that
block TNF-a and IL-17A. These medications can inhibit radio-
graphic progression, control signs and symptoms, improve phys-
ical function, prevent disability, and improve quality of life. Thus,
dermatologists, by detecting PsA early, are key to preventing dis-
ability in these patients. Treatments should be selected that tar-
get the most burdensome or progressive PsA clinical domain(s)
for each patient based on the efficacy profiles of available treat-
ments for these domains.
Acknowledgments
Technical assistance with editing and styling of the manuscript for
submission was provided by Oxford PharmaGenesis Inc. and was
funded by Novartis Pharmaceuticals Corporation. The authors
were fully responsible for all content and editorial decisions and
received no financial support or other form of compensation
related to the development of this manuscript.
Disclosure statement
Alice Gottlieb: Consultant/advisory board agreements for Janssen,
Celgene, Bristol-Myers Squibb, AbbVie, UCB, Novartis, Incyte, Lilly,
Reddy Labs, Valeant, Dermira, Allergan, Sun, XBiotech, and Leo.
Pharmaceutical industry research/educational grants from Janssen,
Incyte, UCB, Novartis, and Lilly, and XBiotech.
Joseph F. Merola: Consultant and/or investigator for Merck
Research Laboratories, Abbvie, Eli Lilly and Company, Novartis,
Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GSK, Almirall,
Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.
Funding
This work was supported by Novartis Pharmaceuticals Corporation.
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