2. INTRODUCTION TO PSORIATIC ARTHRITIS (PSA)
Chronic progressive, inflammatory disorder of the joints and skin1
Characterized by osteolysis and bony proliferation1
Clinical manifestations include dactylitis, enthesitis,
osteoperiostitis, large joint oligoarthritis, arthritis mutilans,
sacroiliitis, spondylitis, and distal interphalangeal arthritis1
PsA is one of a group of disorders known as the
spondyloarthropathies2
Males and females are equally affected3
PsA can range from mild nondestructive disease to a severely
rapid and destructive arthropathy3
Usually Rheumatoid Factor negative3
Radiographic damage can be noted in up to 47% of patients at a
median interval of two years despite clinical improvement with
standard DMARD therapy4
1Taylor
WJ. Curr Opin Rheumatol. 2002;14:98–103.
1Taylor
P. Curr OpinWJ. Curr Opin Rheumatol. 2002;14:98–103.
Rheumatol. 2004;16:366–370.
2Mease P. Curr Opin Rheumatol. 2004;16:366–370.
3Brockbank J, et al. Exp Opin Invest Drugs. 2000;9:1511–1522.
43Brockbank J,Rheumatology. 2003;42:1460–1468.
Kane D, et al. et al. Exp Opin Invest Drugs. 2000;9:1511–1522.
4Kane D, et al. Rheumatology. 2003;42:1460–1468.
2Mease
3. SPONDYLOARTHRITIS, PSORIASIS AND PSA
Spondyloarthritis (SpA)
The prevalence of SpA is comparable to that of RA (0.5–1.9%)1,2
Psoriasis (Pso)
Psoriasis affects 2% of population
Juvenile SpA
3
7% to 42% of patients with Pso will develop arthritis
Undifferentiated
SpA (uSpA)
PsA
Ankylosing
spondylitis (AS)
Arthritis
Psoriatic Arthritis
Reactive
associated with
arthritis
IBD
A chronic and inflammatory arthritis in association with skin psoriasis4
Usually rheumatoid factor (RF) negative and ACPA negative5
Distinct from RA
Psoriatic Arthritis is classified as one of the subtypes of spondyloarthropathies
Characterized by synovitis, enthesitis, dactylitis, spondylitis, skin and nail
psoriasis4
1Rudwaleit
RA: Rheumatoid arthritis
M et al. Ann Rheum Dis 2004;63:535-543; 2Braun J et al. Scand J Rheumatol 2005;34:178-90;
3 Fitzgerald ―Psoriatic Arthritis‖ in Kelley’s Textbook of Rheumatology, 2009;
4Mease et al. Ann Rheum Dis 2011;70(Suppl 1):i77–i84. doi:10.1136/ard.2010.140582;
5Pasquetti et al. Rheumatology 2009;48:315–325
5. EPIDEMIOLOGY OF PSA
•
Recent review undertaken to 20061,2
− Incidence
Europe+North America: 3 to 23.1 cases/105
Japan
0.1 case/105
− Prevalence
•
Europe+North America 20 and 420 cases/105
Japan
1 case/105
Population-based study/Minnesota (CASPAR criteria)2,3
− Incidence
7.2 cases/105 (men 9.1, female 5.4)
− Prevalence
158 cases/105
The prevalence of PsA is assumed to be larger than expected, since
enthesitis associated with PsA can develop without symptoms or
signs that are recognizable by patients themselves or the physicians4
1
Alamos et al. J Rheumatol 2008;35:1354-8;
F et al. J Rheumatol 2009;36:361-7;
3Editorial by Chaudran. J Rheumatol 2009;36:213-5;
4Takata et al. J Dermatol Sci. 2011 Nov;64(2):144-7
2Wilson
6. ETIOLOGY
Genetic Factors
Immunologic Mechanisms
Environmental
Trauma – Koebner phenomenon: psoriatic lesions arising
at site of trauma (24-52%); development of PsA after
trauma to joint.
Bacterial infections - association between guttate
psoriasis and streptococcal pharyngitis; up to 30% of PsA
synovial tissue-derived T cells proliferate following
exposure to group A strep
7. GENETIC FACTORS
Has been known to occur in families
Up to 40% psoriasis or PsA have a family
history in first degree relative
The disease is 50 times more likely to occur
in first degree relative than controls
Tends to be concordant among monozygotic
twins more commonly than dizygotic
8. GENETICS AND HLA ANTIGENS
Concordance rate monozygotic twins of 35-70%, 1220% for dizygotic twins.
HLA-B27 in the presence of HLA-DR7, HLA-DQ3 in
the absence of HLA-DR7, and HLA-B39 are predictors
for disease progression, HLA-B22 is protective.
HLAB27 less than AS or Reiter’s; some psoriasis and
SpA are HLA B27 (-)
PsA and HLA B27 who do not have SpA
Some patients with HLA DR4: PsA with polyarthritis
9. ROLE OF TNF
Released predominantly by cells of the
monocyte/macrophage lineage
Accumulation of T-cells, infiltration of
synovium: TNF-mediated production of
factors that attract T-cells – monocyte
chemoattractant protein-1 and macrophage
inflammatory protein 3 alpha
Induces lymphocyte and neutrophil migration
into synovium
10. TNF IN PSA
High levels of TNF-α in PsA synovium
Marked upregulation of TNF-α in PsA synovial
membrane
Inflammation of synovium, enthesis and bone
TNF-α transgenic mice – bone destruction
Promotes release of matrix-degrading
metalloproteinases
Enhances secretion of pro-inflammatory cytokines
(IL-1, IL-6, IL-8)
Potentiates osteoclastic bone resorption
14. CLASSICAL DESCRIPTION OF PSA USING THE
DIAGNOSTIC CRITERIA OF MOLL AND WRIGHT
Including 5 clinical patterns:
Asymmetric mono-/oligoarthritis (~30% [range 12-70%])1-4
Symmetric polyarthritis (~45% [range 15-65%])1-4
Distal interphalangeal (DIP) joint involvement (~5%)1
Axial (spondylitis and Sacroiliitis) (HLA-B27) (~5%)1,3
Arthritis Mutilans (<5%)1,3
• However patterns may change over time and are therefore not useful for
classification 5
HLA: Human leucocytes antigen
References see notes
15. ASYMMETRICAL OLIGOARTICULAR ARTHRITIS
MC type (70%)
Asymmetrical similar
to low grade gout.
Sausage like swelling
of one or more digit
(dactylitis).
A large joint, such as
the knee, is also
commonly involved.
Usually, <5 joints are
affected at any one
time.
Enthesitis
Flexor sheath
synovitis
16. HALLMARK CLINICAL FEATURES IN PSA
P so ria tic A rth ritis
D a ctylitis
E n th e sitis
Ritchlin C. J Rheumatol. 2006;33:1435–1438.
Helliwell PS. J Rheumatol. 2006;33:1439–1441.
17. DACTYLITIS
• Diffuse swelling of a digit may be acute, with painful
inflammatory changes, or chronic wherein the digit remains
swollen despite the disappearance of acute inflammation1
• Also referred to as
―sausage digit‖1
• Recognized as one
of the cardinal
features of PsA,
occurring in up
to 40% of patients1,2
• Feet most commonly
affected1
• Dactylitis involved
digits show more
radiographic damage1
ACR Slide Collection on the Rheumatic Diseases; 3rd edition. 1994.
1Brockbank J, et al. Ann Rheum Dis. 2005;64:188–190.
2Veale D, et al. Br J Rheumatol. 1994;33:133–38.
18. DEFINITION OF ENTHESITIS
Entheses
are the regions at
which a tendon, ligament, or
joint capsule attaches to
bone1
Inflammation at the
entheses is called enthesitis
and is a hallmark feature of
PsA1,2
Pathogenesis of enthesitis
has yet to be fully
elucidated2
Isolated peripheral
enthesitis may be the only
rheumatologic sign of PsA in
a subset of patients3
1McGonagle
D. Ann Rheum Dis. 2005;64(Suppl II):ii58–ii60.
2Anandarajah AP, et al. Curr Opin Rheumatol. 2004;16:338–343.
3Salvarani C. J Rheumatol. 1997;24:1106–1140.
19. SYMMETRICAL POLYARTHRITIS
-
-
-
Rheumatoid like pattern.
15%
Hands, wrists, ankles, and feet
may be involved.
D/D from RA by
DIP joint involvement,
Morning stiffness
Fusiform deformity
Wind swept deformity
Relative asymmetry,
Subcutaneous nodules absent.
RF negative.
Milder, with less deformity.
20. DISTAL INTERPHALANGEAL ARTHROPATHY
Classical form
Less common 16%
Involvement of the nail with significant inflammation of the
paronychia and swelling of the digital tuft may be
prominent,
30 pits with inflammatory arthritis of DIP joints considered
diagnostic.
22. ARTHRITIS MUTILANS
Rare form
1-5%
Some reports suggest up to 16% of patients.
Resorption of bone (osteolysis), with dissolution of the
joint, is observed as the "pencil-in-cup" radiographic
finding and leads to redundant, overlying skin with a
telescoping motion of the digit.
This "opera-glass hand" is M>F and is more frequent
in early-onset disease.
23. ARTHRITIS MUTILANS, A TYPICALLY
PSORIATIC PATTERN OF ARTHRITIS,
WHICH IS ASSOCIATED WITH A
CHARACTERISTIC "PENCIL-IN-CUP"
RADIOGRAPHIC APPEARANCE OF
DIGITS.
Arthritis mutilans (ie,
"pencil-in-cup"
deformities).
24. SPONDYLITIS WITH OR WITHOUT SACROILIITIS
-
-
Affect 5% of patients and has a male predominance.
Can occur in conjunction with other subgroups of PA.
Spondylitis may occurWithout radiologic evidence of sacroiliitis, which
frequently tends to be asymmetrical,
May appear radiologically without the classic
symptoms of morning stiffness in the lower back.
Thus, the correlation between symptoms and
radiologic signs of sacroiliitis can be poor.
Vertebral involvement differs from that observed in AS.
25.
-
-
Vertebrae are affected
asymmetrically, and the
atlantoaxial joint may be
involved with erosion of the
odontoid and subluxation
(with attendant neurologic
complications).
Therapy may limit
subluxation-associated
disability.
Unusual radiologic feature
nonmarginal asymmetrical
syndesmophytes
(characteristic),
paravertebral ossification,
and,
less commonly, vertebral
fusion with disk calcification.
Lateral radiograph of the cervical spine
shows syndesmophytes at the C2-3 and
C6-7 levels, with zygapophyseal joint fusio
26. PATTERNS MAY CHANGE OVER TIME AND ARE
THEREFORE NOT USEFUL FOR CLASSIFICATION
Clinical subgroups at baseline and follow-up:
Monoarthritis
Monoarthritis
Oligoarthritis
Oligoarthritis
DIP
DIP
Polyarthritis
Polyarthritis
Spondyloarthritis
Spondyloarthritis
Mutilans
Mutilans
No clinical evidence of
joint disease
McHugh et al. Rheum 2003;42:778-783
27. CASPAR CRITERIA FOR THE CLASSIFICATION OF
PSA
Inflammatory articular disease (joint, spine, or
entheseal)
With 3 points from following categories:
− Psoriasis: current (2), history (1), family history (1)
− Nail dystrophy (1)
− Negative rheumatoid factor (1)
− Dactylitis: current (1), history (1) recorded by a
rheumatologist
− Radiographs: (hand/foot) evidence of juxta-articular new
bone formation
Specificity 98.7%, Sensitivity 91.4%
Taylor et al. Arthritis & Rheum 2006;54: 2665-73
28. SIGNS AND SYMPTOMS
Morning stiffness lasting >30 min in 50% of patients1
Ridging, pitting of nails, onycholysis – up 90% of patients vs
nail changes in only 40% of psoriasis cases2,3
Patients may present with less joint tenderness than is
usually seen in RA1
Dactylitis may be noted in >40% of patients2,4
Eye inflammation (conjunctivitis, iritis, or uveitis) — 7–33%
of cases; uveitis shows a greater tendency to be bilateral
and chronic when compared to AS2
Distal extremity swelling with pitting edema has been
reported in 20% of patients as the first isolated manifestation
of PsA5
1Gladman
DD. In: Up To Date. Available at: www.uptodate.com. Accessed December 3, 2004.
2Taurog JD. In: Harrison's Online McGrawHill. Available at:
http://www3.accessmedicine.com/popup.aspx?aID=94996&print=yes. Accessed January 2,2005.
3Gladman DD. Rheum Dis Clin N Amer. 1998;24:829–844.
4Veale D, et al. Br J Rheumatol. 1994;33:133–38.
5Cantini F, et al. Clin Exp Rheumatol. 2001;19:291–296.
29. MAIN FEATURES OF PSA
*Low levels of RF and ACPA can be found in 5-16% of patients; **To a lesser degree than in RA
***Spinal disease occurs in 40-70% of PsA patients
Helliwell PS & Taylor WJ. Ann Rheum Dis 2005;64(2:ii)3-8
Fitzgerald ―Psoriatic Arthritis‖ in Kelley’s Textbook of Rheumatology, 2009
30. MAIN FEATURES AND THEIR FREQUENCY
Back involvement (50%)1
Skin Involvement
In nearly 70% of patients,
cutaneous lesions precede
the onset of joint pain, in
20% arthropathy starts
before skin manifestations,
and in 10% both are
concurrent. 6
DIP involvement (39%)2
Nail psoriasis (80%)4, 5
Dactyilitis (48%)3
Enthesopathy (38%)2
DIP: Distal interphalangeal
1Gladman
D et al. Arth & Rheum 2007;56:840; 2 Kane. D et al. Rheum 2003;42:1460-1468
3 Gladman D et al. Ann Rheum Dis 2005;64:188–190; 4Lawry M. Dermatol Ther 2007;20:60-67
5Jiaravuthisan MM et al. JAAD 2007;57:1-27; 6Yamamoto Eur J Dermatol 2011;21:660-6
31. COMORBIDITIES IN PSA PATIENTS
Ocular inflammation1
(Iritis/Uveitis/ Episcleritis)
IBD2
Pso patients6-8
• Psychosocial burden
• Reactive depression
• Higher suicidal ideation
• Alcoholism
Metabolic Syndrome3-5
• Hyperlipidemia
• Hypertension
• Insulin resistent
• Diabetes
• Obesity
Higher risk of
Cardiovascular disease (CVD)
Nail pitting, transverse depressions,
and subungual hyperkeratosis
1Qieiro
et al. Semin Arth Rheum 2002;31:264; 2Scarpa et al. J Rheum 2000;27:1241; 3Mallbris et al. Curr Rheum Rep 2006;8:355;
et al. J Am Acad Derm 2006;55:829; 5Tam et al. 2008;47:718; 6Kimball et al. Am J Clin Dermatol 2005;6:383-392;
7Naldi et al. Br J Dermatol 1992;127:212-217; 8Mrowietz U et al. Arch Dermatol Res 2006;298(7):309-319
4Neimann
37. Pharmaceutical treatments for psoriatic arthritis: corticosteroid
Generic Name
Manufacturer U.S.
Trade Name(s)*
How Supplied
Usual Adult Dose
Methyl-prednisolone
Multiple
®
Medrol , Depo®
Medrol , Solu®
Medrol
Acetate - Injectable
IM—20, 40, and 80
mg/ml
Sodium succinate Injectable:
IM—40, 125, and 500
mg, 1 and 2 g vials
Oral:
Tabs—2, 4, 8, 16, and
32 mg
•Acetate:IM—10 to 80
mg every 1 to 2
weeks
•Intra-articular,
intralesional —4 to 80
mg every 1 to 5
weeks
•Sodium
succinate:IM—10 to
80 mg daily
•IV—10 to 40 mg
every 4 to 6 hours; up
to 30 mg/kg every 4
to 6 hours
•Oral:2 to 60 mg in 1
to 4 divided doses to
start, followed by
gradual reduction
Prednisone
Multiple
®
Deltasone ,
®
Sterapred ,
®
LiquiPred
Oral Solution—1 and
5 mg/ml
Tabs—1, 2.5, 5, 10,
20, and 50 mg
Use lowest effective
dose (5–60 mg/day)
Prednisolone
Multiple
®
Orapred ,
Oral Solution/Syrup—
5, 15, and 20 mg/5 ml
Use lowest effective
dose (5 to 7.5
®
40. Mechanism of action, dosing schedule and
major risks with the biologic therapies
41. Generic Name
Manufacturer
U.S. Trade
Name(s)*
Injectable Supply
Usual Adult Dose
Abatacept
Bristol
Myers
Squibb
®
Orencia
250 mg vial
IV—Dosed according to body weight
(<60 kg=500 mg; 60–100 kg=750 mg;
>100 kg=1,000 mg); dose repeated at 2
weeks and 4 weeks after initial dose, and
every 4 weeks thereafter
SQ—may give weight-based IV loading
dose, then 125 mg SQ once weekly
Adalimuma
b
Abbott
®
Humira
40 mg/0.8 ml, 20
mg/0.4 ml prefilled
syringe
SQ—40 mg every other week alone or in
combination with other DMARDs
Anakinra
Amgen
®
Kineret
100 mg/0.67 ml
syringe
SQ—100 mg/day; dose should be
decreased to 100 mg every other day in
renal insufficiency
Certolizuma
a
bPegol
UCB
®
Cimzia
200 mg powder for
reconstitution, 200
mg/ml solution
SQ—initial dose of 400 mg (as 2 SQ
injections of 200 mg), repeat dose 2 and
4 weeks after initial dose; Maintenance
dose is 200 mg every other week (may
consider maintenance dose of 400 every
4 weeks)
Etanercept
Amgen
Pfizer
Immunex
®
Enbrel
50 mg/ml in 25 mg
or 50 mg single
use prefilled
syringe
SQ—50 mg once weekly with or without
MTX
42. Golimuma
b
Centocor
Ortho
Biotech
®
Simponi
50 mg/0.5
ml syringe
Infliximab
Centocor
Ortho
Biotech
®
Remicade
100 mg in a IV—5 mg/kg at 0, 2 and 6 weeks
20 ml vial
followed by maintenance every 8
weeks thereafter; may be given with
or without MTX
Rituximab
Biogen
Idec /
Genentech
®
Rituxan
100 mg/10
ml and 500
mg/50 ml
vial
Tocilizuma
b
Genentech
/ Roche
®
Actemra ,
RoActemra
80 mg/4 ml, IV—4 mg/kg every 4 weeks; increase
200 mg/10
to 8 mg/kg every 4 weeks based on
ml, 400
clinical response
mg/20 ml
vial
®
SQ—50 mg once per month, alone or
in combination with MTX
IV—1,000 mg IV infusion separated by
2 weeks (one course) every 24 weeks
or based on clinical evaluation, but
not sooner than every 16 weeks
43. OTHER AGENTS
Several other agents have been tried, including vitaminD3, bromocriptine, peptide T, and fish oils, but their
efficacy remains to be proven.
Antimalarials, particularly hydroxychloroquine
(Plaquenil), are usually avoided in patients with psoriasis
for fear of precipitating exfoliative dermatitis or
exacerbating psoriasis.
However, 2 studies showed that these reactions did not
occur in patients who were treated with
hydroxychloroquine; therefore, this drug is occasionally
used to treat PA.
Systemic corticosteroids are usually avoided because of
possible rebound of the skin disease upon withdrawal.
44. SURGICAL CARE IN PSORIATIC ARTHRITIS
Arthroscopic synovectomy has been effective in treating
severe, chronic, monoarticular synovitis.
Joint replacement and forms of reconstructive therapy
are occasionally necessary.
Patients in severe pain or with significant contractures
may be referred for possible surgical intervention;
however, high rates of recurrence of joint contractures
have been noted after surgical release, especially in the
hand.
45.
Hip and knee joint replacements have been
successful.
Arthrodesis and arthroplasty have also been used on
joints, such as the thumb PIP joint.
The wrist often spontaneously fuses, and this may
relieve the patient's pain without surgical intervention.
For arthritis mutilans, surgical intervention is usually
directed toward salvage of the hand; combinations of
arthrodesis, arthroplasty, and bone grafts to lengthen
the digits may be used.
46. CONSULTATIONS AND MONITORING IN PSORIATIC
ARTHRITIS
If the patient's physiatrist feels uncomfortable with
prescribing medications for PA, referral to a
rheumatologist with more experience with these agents
may be advisable.
The physiatrist may then concentrate on functional
restoration of the patient.
Referral to a surgeon should be considered for
appropriate patients.
Children with juvenile PA should be examined by an
ophthalmologist annually to check for the several forms
of eye inflammation usually associated with various
forms of juvenile arthritis.
In addition, consultation with an orthopedic surgeon is
warranted for individuals who may benefit from joint
replacement, arthrodesis, or contracture release.
47. DIETARY CONSIDERATIONS
For people who have morning stiffness, the optimal
time for taking an NSAID may be after the evening
meal and again upon awakening.
Taking NSAIDs with food can reduce stomach
discomfort.
Any NSAID can damage the mucous layer and cause
ulcers and GI bleeding when taken for long periods.
Cyclooxygenase (COX)–2 selective inhibitors are
associated with a lower prevalence of gastric ulcer
formation.
48. PHYSICAL THERAPY IN PSORIATIC ARTHRITIS
The rehabilitation treatment program should be
individualized and should be started early in the
disease process. Such a program should consider the
use of the following:
Rest - Local and systemic
Exercise - Passive, active, stretching, strengthening,
and endurance
Modalities - Heat, cold
Orthotics - Upper and lower extremities, spinal
49. DETERRENCE AND PREVENTION
Lithium and withdrawal from systemic corticosteroids are
well known to cause disease flare-ups.
Other drugs that have been implicated include beta
blockers, antimalarials (although, as previously
mentioned, evidence suggests that hydroxychloroquine
does not exacerbate skin lesions), and NSAIDs.
If skin lesions worsen with an NSAID, switch to a
different family of NSAID.
Prevention includes rest and exercise.
Joint protection, including splints, braces, and other
supports, may be helpful.
No definitive prevention exists, because this is a chronic
disease that can wax and wane.
#### PLEASE DO NOT DELETE CONTENT BELOW THIS LINE ! ############### Presentation 'GLM_OPT02_GLM Optimize PsA_r00_05AUG10.ppt' created on Wednesday, 4 August, 2010 ###########Author: GIB1 Purpose: Optimize slide decks QA: 04-Aug-10 Review By: 04-Feb-11Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 9/108 Golimumab-Specific Deck: Yes
#### PLEASE DO NOT DELETE CONTENT BELOW THIS LINE ! ############### Presentation 'GLM_OPT02_GLM Optimize PsA_r00_05AUG10.ppt' created on Wednesday, 4 August, 2010 ###########Author: GIB1 Purpose: Optimize slide decks QA: 04-Aug-10 Review By: 04-Feb-11Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 9/108 Golimumab-Specific Deck: Yes
#### PLEASE DO NOT DELETE CONTENT BELOW THIS LINE ! ############### Presentation 'GLM_OPT02_GLM Optimize PsA_r00_05AUG10.ppt' created on Wednesday, 4 August, 2010 ###########Author: GIB1 Purpose: Optimize slide decks QA: 04-Aug-10 Review By: 04-Feb-11Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 14/108 Golimumab-Specific Deck: Yes
Two important features of PsA that cause significant problems for PsA patetients. Data to be shared later will show significant benefit of anti-tnf therapy in this regard.
#### PLEASE DO NOT DELETE CONTENT BELOW THIS LINE ! ############### Presentation 'GLM_OPT02_GLM Optimize PsA_r00_05AUG10.ppt' created on Wednesday, 4 August, 2010 ###########Author: GIB1 Purpose: Optimize slide decks QA: 04-Aug-10 Review By: 04-Feb-11Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 17/108 Golimumab-Specific Deck: Yes