Psoriatic arthritis

Neil McHugh
Royal National Hospital for Rheumatic Diseases
University of Bath
 The Spondyloarthropathies
Axial Spondyloarthropathy Peripheral joint arthritis
• Features
• Spondylitis
• Uveitis
• Enthesitis Psoriatic arthritis
• Psoriasis Ankylosing
• IBD Spondylitis

• Familial Reactive
Non- arthritis
• B27 related radiographic Undifferentiated
• Th17/IL23 SPA SPA

Enteropathic
arthritis
Psoriasis and Arthritis
V Wright
Ann Rheum Dis 1956, 15, 348 Topographical association between
nail disease and DIPJ involvement

‘This arthritis was less severe

than rheumatoid arthritis, and
was characterized by distal
interphalangeal joint
involvement, erosion of the
terminal phalanges, and a
greater incidence of sacro-iliac
joint changes.’
 Burden of psoriatic arthritis
• Joint damage in 50% within 2 years
of disease
• Reduced quality of life similar
to rheumatoid arthritis
• Comorbidities – e.g. obesity, cardiovascular
disease, uveitis
• One in three unemployed
• High direct health costs
(£4832 per patient-year)

Husted Arthritis Rheum 2001

Sokoll J Rheumatol 2001
Lindqvist J Rheumatology 2008
Kane et al Rheumatology 2003
Diagnosis of psoriatic arthritis
 Moll and Wright subgroups of psoriatic arthritis

Arthritis Mutilans
Predominantly DIP Disease

Polyarthritis

Oligoarthritis Spondylitis

Seminar Arthritis Rheum 1973

 The CASPAR criteria
To meet the CASPAR criteria a patient must have an inflammatory
articular disease (joint, spine or entheseal) and ≥ 3 points from:
1. Current psoriasis 2 points
or Personal history of psoriasis 1 point
or FH of psoriasis 1 point
2. Current psoriatic nail dystrophy 1 point
3. Negative RF 1 point
4. Current or Rheumatologist confirmed dactylitis 1 point
5. Juxta-articular new bone formation 1 point

Taylor et al 2006. Arthritis and Rheum; 54, 2665-2673

 Psoriatic arthritis
• Skin psoriasis affects 2-3% of
normal population often with
nail disease
• About 30% of individuals with
psoriasis develop a distinct
form of inflammatory arthritis
called psoriatic arthritis
• Estimated 400,000 in England
 Differential diagnosis from Rheumatoid arthritis
Features Psoriatic arthritis Rheumatoid arthritis
Number of joints involved 30-50% with oligoarthritis Predominantly polyarthritis
Joint involvement Any joint, including distal Spares distal interphalangeal joints
interphalangeal joints

Enthesitis Typical, clinically present in up to 80% Not typical

Dactylitis Present in 30% Not typical
Axial involvement Axial spondyloarthritis phenotype Erosive cervical disease
Skin/nail disease Psoriasis in 80%, nail disease in 60% Background population prevalance
Serology Usually RhF and ACPA negative Usually RhF and/or ACPA positive

Typical radiographic changes Periosteal new bone formation Erosion and osteopenia
 Radiographic and MRI features of psoriatic arthritis

Tillett and McHugh Oxford Textbook PsA 2017 McGonagle and Tan Clin Exp Rheum 2015
Time interval from first psoriasis record to first PsA record
comparing CPRD to Bath Psoriatic arthritis cohort

Clinical Practice Research Datalink RNHRD PsA Database

• Median interval between psoriasis • Median interval between psoriasis
and PsA 8 years (excluding synchronous and PsA 7 years (excluding synchronous
onset 9 years) onset 13 years)
• 60% diagnosed within 10 years • 57% diagnosed within 10 years
 Risk factors for arthritis in psoriasis

Life style Obesity, smoking

Clinical Nail psoriasis, severity or
pattern of psoriasis
Imaging Ultrasound evidence of
enthesitis
Genetic HLA-B27, IL13, PTPN22
Biomarkers
Other DC-STAMP. hsCRP, MMP-3,
Biomarkers DKK-1, M-CSF, CPII:C2C
Psoriatic Arthritis is Associated with Diagnostic Delay and Worse
Outcome at 3 Months when Compared with Rheumatoid Arthritis:
Results from the UK National Audit for Inflammatory Arthritis
Median time to diagnosis in weeks

PsA (n=1016) RA (n=1016)

Symptoms to GP presentation 8.9 6.6
GP presentation to referral 5.4 4
GP presentation to diagnosis 12.1 9.7
Symptoms to diagnosis 28.6 21.6

Adjusted for age, sex, ethnicity and deprivation index; P<0.02 for all between-group comparisons

Holland et al EULAR 2017

Psoriatic Arthritis is Associated with Diagnostic Delay and Worse
Outcome at 3 Months when Compared with Rheumatoid Arthritis:
Results from the UK National Audit for Inflammatory Arthritis

Holland et al EULAR 2017

How important is detection of early psoriatic arthritis?
• Recent meta-analysis suggest between 10-15 %
prevalence of undiagnosed PsA in dermatology
clinics1
• Delay in diagnosis may be associated with poor
outcome
• Most studies are retrospective and have selection
and recall bias
• NICE recommends annual screening for patients
in primary care on treatment for psoriasis
• At least 40% people with psoriasis not on treatment
or not attending healthcare2
1 Vilani et al JAAD 2015
2 Lebwohl AJCD 2015
Assessment of psoriatic arthritis
Psoriatic arthritis endpoints used in clinical trials
ACR Response Criteria: 20%, 50%, 70%
Tender and swollen joint score (modified for PsA to include DIP and CMC joints)
3/5: patient global, physician global, patient pain, HAQ, acute phase reactant (ESR,
CRP)

Psoriatic Arthritis Response Criteria (PsARC)*

Improvement in at least 2 of 4 criteria, including:
 Physician global assessment (0-5)
 Patient global assessment (0-5)
 Tender joint score (>30%)
 Swollen joint score (>30%)
Improvement in at least 1 of 2 joint scores
No worsening in any criteria
Domains of psoriatic disease
 CPDAI (composite psoriatic disease activity index)
None (0) Mild (1) Moderate (2) Severe (3)
Peripheral ≤ 4 joints; normal ≤ 4 joints but function > 4 joints and function
function (HAQ <0.5) impaired; or > 4 joints, impaired
Arthritis normal function

Skin Disease PASI ≤ 10 and DLQI PASI ≤ 10 but DLQI >10; PASI > 10 and DLQI > 10
≤ 10 or PASI > 10 but DLQI ≤
10

Enthesitis ≤ 3 sites; normal ≤ 3 sites but function >3 sites and function
function (HAQ <0.5) impaired; or >3 sites but impaired
normal function

Dactylitis ≤ 3 digits; normal ≤ 3 digits but function >3 digits and has function
function (HAQ <0.5) impaired; or >3 digits but impaired
normal function

Spinal Disease BASDAI <4; normal BASDAI >4 but normal BASDAI >4 and function
function (ASQol < 6) function; BASDAI <4 but impaired
function impaired
 ACR 20 66/68 joint
PsARC score
PASI 75 BASDAI
CPDAI ACTIVITY PASI score
PASDAS NAPSI
AMDF Enthesitis score
DAPSA

Reversible HAQ
ASQOL
DLQI
SF36
Disease EQ5D
WPAI
Severity*
Sharp score Patient reported outcomes
Mortality

Irreversible Impact of
Damage
Musculoskeletal Disease
Psychosocial
Cardiovascular

*Total effect of disease on organ function

Do we have the correct outcome measures for
psoriatic arthritis?
 The EULAR Psoriatic Arthritis Impact of Disease
Domain od Health Relative importance in the PSAID-12 Relative importance in the PSAID-9
score for clinical practice score for clinical trials
Pain 15 17.4
Fatigue 10 13.1
Skin problems 10 12.1
Work and/or leisure activities 10 11.0
Functional capacity 10 10.7
Discomfort 10 9.8
Sleep disturbance 10 8.9
Coping 5 8.7
Anxiety 5 8.5
Embarrassment and/or shame 5 N/A
Social participation 5 N/A
Depression 5 N/A

Gossec et al 2015 Ann Rheum Dis

International patient and physician consensus on a psoriatic arthritis core outcome set
for clinical trials
Ana-Maria Orbai, Maarten de Wit, Philip Mease, Judy A Shea, Laure Gossec, Ying Ying Leung, William Tillett, Musaab
Elmamoun, Kristina Callis Duffin, Willemina Campbell, Robin Christensen, Laura Coates, Emma Dures, Lihi Eder, Oliver
FitzGerald, Dafna Gladman, Niti Goel, Suzanne Dolwick Grieb, Sarah Hewlett, Pil Hoejgaard, Umut Kalyoncu, Chris
Lindsay, Neil McHugh, Bev Shea, Ingrid Steinkoenig, Vibeke Strand, Alexis Ogdie

Revised 2016 OMERACT core set domains for psoriatic arthritis

Ann Rheum Dis 2017

Treatment and guidelines
Advancing treatments for psoriatic arthritis
secukinumab, brodalumab,
Early treatments: etanercept tofacitinib,
ustekinumab,
NSAIDs, apremilast guselkumab,
corticosteroids The first clazakizumab,
biological
therapy: TNFi 4 Authorisations ixekizumab,
infliximab, for therapies with ABT-122
Methotrexate, adalimumab alternative MoAs
sulfasalazine etc golimumab
certolizumab
PsA described More targets and
pegol
as a clinical more options
RA csDMARDs1
entity More TNFi
2016 and
c.1960s 1990s 2000 2005 2009 2014 2015
The Future
Advances in the treatment of psoriatic arthritis
• TNF inhibition
• Other biologicals
• IL12/23
• IL17
• Small molecules
• PDE4i
• Treatment strategies
 Efficacy of traditional DMARDs vs anti-TNF

LFN: . Peter Kaltwasser, et al., ; CSA: Salvarani et al; SSZ: Salvarani et al; MTX: Kinsgley et al.
 Anti-TNF treatments: ACR responses at 12/14 weeks

Trial n ACR20% ACR50% ACR70%

Rx P Rx P Rx P
Adalimumab 315 58 14 36 4 20 1
Certolizumab 409 58 24 36 11 25 3
Etanercept 205 59 15 38 4 11 0
Golimumab 405 52 8 32 3.5 18 0.9
Infliximab 200 58 11 36 3 15 1

• Effective for all domains of disease and slow structural damage

• Risk of infection (e.g. mycobacterium)
• Risk of malignancy and safety in pregnancy and heart failure?

Adapted from Mease Rheum Dis Clin N Am 2015

 Predictors of response to anti-TNF
• Positive predictors
• Male gender
• High CRP
• Younger age
• Concomitant methotrexate
• Negative predictors
• Smoking
• Obesity
• High HAQ-DI
 Effectiveness of switching anti-TNF
-registry data
• South Swedish Arthritis Treatment Group Register
• ACR20 response at 12 weeks falls to 47% for first time switches and
and to 22% for second time switches
• Median drug survival time 64 months for first time switches and 14
months for second-time switches
• Higher HAQ predicted premature drug withdrawal
• Results suggest that other therapeutic options should be considered
after 2nd course of anti-TNF

Kristensen et al J Rheum 2016:43:81-87

Advances in the treatment of psoriatic arthritis
• TNF inhibition
• Other biologicals
• IL12/23
• IL17
• Small molecules
• PDE4i
• Treatment strategies
 IL-12 and IL-23 cytokines
• TNF inhibition
• Other biologicals
• IL12/23
• IL17
• Small molecules
• PDE4i
• Treatment strategies

Teng et al Nature Med 2015:21:719

IL12 and IL23 as targets for therapy

Patel DD and Kuchroo VK Immunity Dec 2015

 Indications for Ustekinumab
• Recommended by NICE as a possible treatment, alone or with
methotrexate, for adults with active psoriatic arthritis, if TNFi
contraindicated or failed one or more TNFis
• 90 mg dose at same cost as 45 mg dose for patients > 100 kg
• Stopped after 24 weeks if not working
• Ideal patient
• High psoriasis burden
• TNFi refractory, especially primary non-responder
• TNF adverse events ( e.g. lupus-like reaction) or contraindications (recurrent
infections?)
IL23R resident T cells present at the enthesis

Sherlock et al Nature Med 2012

Lories RJ & IMcInnes IB Nature Medicine 2012
Advances in the treatment of psoriatic arthritis
• TNF inhibition
• Other biologicals
• IL12/23
• IL17
• Small molecules
• PDE4i
• Treatment strategies
IL-17 as a target for treatment in psoriatic arthritis

• Interleukin-17A producing cells increased in circulation, joints and skin plaques of

patients with PsA
• Synovium of PsA enriched with IL-17 producing CD4+ effector memory T cells,
CD4-CD8+ T cells and functionally active IL-17RA
Patel DD et al ARD 2013, Raychaudhuri SP et al Mol Cell Biochem 2012, Menon et al Arthritis Rheum 2014
IL-17 isoforms as targets for treatment

Patel DD and Kuchroo VK Immunity Dec 2015

 Apremilast: Mechanism of action
• TNF inhibition
• Other biologicals
• IL12/23
• IL17
• Small molecules
• PDE4i
• Treatment strategies

Busa S & Kavanaugh A Expert Opin. Drug Saf 2015

 Summary of recent findings of new agents
N ACR20 wk16 ACR20 wk24 PASI75 wk24 Delta HAQ

Rx P Rx P Rx P Rx P
PSUMMIT 1 UST 45mg 205 42 23 57 11 -0.25 0
UST 90mg 204 50 23 62 11 -0.25 0
PSUMMIT 2 UST 45mg 103 44 20 51 5 -0.13 0
UST 90 mg 105 44 20 56 5 -0.25 0
PALACE 1 APREM 30mg bd 163 36 12 37 13 21 5 -0.24 -0.09
PALACE 2 APREM 30mg bd 162 34 19 22 2.7
PALACE 3 APREM 30mg bd 159 43 19 42 NA 21 8 -0.20 -0.07
PALACE 4 APREM 30mg bd 139 32 17
FUTURE 1 SECU 150 mg 202 50 17 65 8.3 -0.40 -0.17
FUTURE 2 SECU 150 mg 100 52 15 48 16 -0.48 -0.31
Advances in the treatment of psoriatic arthritis
• TNF inhibition
• Other biologicals
• IL12/23
• IL17
• Small molecules
• PDE4i
• Treatment strategies
• Minimal disease activity (MDA) achieved in tight control arm if 5 of
the following criteria are met:
• Tender joint count (0-68): ≤1
• Swollen joint count (0-66): ≤1
• Patient global activity VAS (0-100): ≤20
• Patient pain VAS (0-100): ≤15
• HAQ-DI (0-3): ≤0.5
• Tender entheseal points (0-13): ≤1
• PASI (0-72): ≤1 or BSA(0-100): ≤3%
Lancet. 2015 December 19; 386(10012): 2489–2498.
 A treat-to-target strategy has effectiveness in PsA
and current guidelines support this approach
• In TICOPA, a tight control strategy leads to better outcomes (although
greater incidence of AEs) with more patients at MDA and potential
associated cost effectiveness in the long-term.
• 2016 GRAPPA recommendations
• An ultimate goal of therapy is to achieve the lowest possible level of disease
activity in all domains…
• The treat-to-target approach has also become the first
recommendation in 2016 EULAR guidelines

Coates L. C, et al. Lancet. 2015;386:2489─98

Coates L. C, et al. Arthritis Rheum. 2016 May;68(5):1060-71
Gossec L, et al. Ann Rheum Dis. 2016 Mar;75(3):499-510.
2016 EULAR guidelines for psoriatic arthritis:
management of peripheral joint disease

Gossec et al Nat Rev Rheum 2016

2016 EULAR guidelines for psoriatic arthritis:
management of predominant entheseal disease

Gossec et al Nat Rev Rheum 2016

2016 EULAR guidelines for psoriatic arthritis:
management of predominant axial disease

Gossec et al Nat Rev Rheum 2016

Potential therapies to inhibit osteolysis and new bone formation
• Osteolysis • New bone formation
• NSAIDs
• Inhibition of
• Wnt anatagonists
• TNFi (etanecept, infliximab, adalimumab,
golimumab, certilizumab) • BNP antagonists
• IL23 (ustekinumab) • Anti-IL22
• IL17 (sekukinumab)
• PDE4 (Apremilast
• Jak/Stat inhibitors (tofacitinib)
• Anti-RANKL (denosumab)

vs
 Key messages
• Psoriatic arthritis is not uncommon but is frequently undiagnosed
• In addition to skin psoriasis other important risk factors are obesity,
nail disease and HLA-B27
• Significant comorbidities include obesity, uveitis, Crohn’s, and
cardiovascular disease
• Newer treatments (e.g. anti-TNF, anti-IL23, anti-IL17) are more
effective than traditional DMARDS ( e.g. methotrexate) and small
molecule inhibitors are becoming available
• Psoriatic arthritis is not a benign disease