PSORIATIC ARTHRITIS. Elvia Moreta, MD St. Paul Rheumatology 2012

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1 PSORIATIC ARTHRITIS Elvia Moreta, MD St. Paul Rheumatology 2012

2 RESEARCH DISCLOSURE ABBOTT BMS CENTOCOR GENENTEC LILLY NOVARTIS ROCHE SAVIENT UCB CONSULTANT ABBOTT UCB MEMBER ABIM fellow CORRONA Consortium of Rheumatology Researchers of NA GRAPPA Group of Researchers Against Psoriasis & Psoriatic Arthritis ISEMIR International Society of Extremity MRI (executive board) ISCD International Society of Clinical Densitometry

of NA GRAPPA Group of Researchers Against Psoriasis & Psoriatic Arthritis ISEMIR

3 Psoriatic Disease Skin involvement present in 1/3 of PsA 1 Approximately 25% PsO manifest Psoriatic arthritis 2 FHx Pso or PsA in 1 st degree relative > 40% PsA patients 3 Subclinical intestinal & duodenal inflammation is present in subset of PsA 4 Uveitis observed in 15 40% of PsA 5 PsA have higher prevalence metabolic syndrome & early MI than age-matched controls 6 Metabolic syndrome & other CV risk factors observed in PsO +/- presence of PsA 7 1. Gladman DD. Psoriatic Arthritis. Rheum Dis Clinic North Am 1998;24: Mease P. Curr Opin Rheum Little H, Harvie JN, et al. Can Med Asso J 1975;112: Lindqvist U. J Rheum 2006 & Schatterman L. J Rheum 1995; 22: Pavia E. Ann Rheum Dis Gelfand J. JAMA Husni ME, et al. ACR Chicago, IF Nov 2011 poster 500.

CV risk factors observed in PsO +/- presence of PsA 7 1. Gladman DD. Psoriatic Arthritis. Rheum Dis Clinic North Am 1998;24:829-44. 2. Mease P. Curr Opin Rheum 2004. 3. Little H, Harvie JN, et al.

4 Psoriatic Arthritis: Clinical Features 97% have peripheral arthritis (20% destructive)* 1. RA like (RF often negative, 30% are positive) 30-50% is most common phenotype 2. DIP (mimics OA but asymmetrical) associated with nail disease, 10-15% 3. Dactylitis (mimics gout) whole digit inflammation - 50% & associated with risk of progressive X-ray 4. Asymmetric small or large joint, oligoarticular 5. Arthritis mutilans can present with any clinical presentation

DIP (mimics OA but asymmetrical) associated with nail disease, 10-15% 3.

5 PSORIATIC ARTHRITIS : Features Clinical Spondylitic 25 70% 1 - commonly have iritis and HLA-B27+ - older patient with longer disease duration - many are asymptomatic - high prevalence of cervical spine - outcome measures for AS are applicable (BASDAI) Enthesitis : + pain & tendon insertion - Achilles,plantar fasciitis, tibial tuberosity, epicondylitis 1. Gladman DD et al. Curr Rheum Rep 2009; 9: 455.

- outcome measures for AS are applicable (BASDAI) Enthesitis : + pain & swelling @ tendon insertion -

6 Dactylitis

7 DIP

8 Polyarticular

9 Enthesitis

10 Nail

11 Psoriatic Arthritis Epidemiology Incidence approximately 6 per 100,000/yr; Peak yrs, M = F Prevalence 1 2 per 1000 in US Prevalence of PsA among PsO ranges 4 30% 1. Zachariae H. Prevalence of joint disease in pts. with PsO: Implications for therapy. Am J Clin Derm 2003; 4: Ibrahim G. et al. The prevalence of PsA in people with PsO. Arthritis Rheum 2009; 61: 1373 PsO precedes in 70% of PsA; 15% present concurrently; PsA presents before PsO in 15% in adults, more often in children Kavanaugh A, et al. New Developmets in Rheumatic Dis (vol 3, no.2);3. Prospective study of Pso w/out presentation had incidence of new PsA 2%/yr based on CASPAR Eder L. et al. Incidence of Arthritis in Prospective Cohort of Psoriasis Patients. Arthritis Care Res (Hoboken) 2011; 63: 619.

Arthritis Rheum 2009; 61: 1373 PsO precedes in 70% of PsA; 15% present concurrently; PsA presents before PsO in 15% in adults, more often in children Kavanaugh A, et al.

12 Psoriatic Arthritis POOR PROGNOSIS 1. Polyarthritis with elevated ESR +/- CRP 2. Joint erosions 3. Inadequate clinical response to traditional therapy High incidence of poor health related quality of life & disability Without prompt therapeutic intervention joint destruction can develop rapidly Over 50% develop deforming arthritis Mortality increased relative to general population Gladman DD, Mease P, et al. Ann Rheum Dis 2005;64 (Suppl 2):

disability Without prompt therapeutic intervention joint destruction can develop rapidly Over 50% develop

13 PSORIASIS AND PsA Clues to Pathogenesis 40% have positive Family History Psoriasis precedes arthritis (70%), but may be absent Male/female ratio 1:1 Association with Class I MHC alleles PsO 62% & PsA 27.9% are + HLA-Cw0602 PsA higher % vs controls are + HLA-B27, B39 +Cw06 have 10 yr gap between Pso & onset PsA +B27 have skin & joint dz. present w/in 1 yr GRAPPA. Stockholm Sweden June 2012.

14 Psoriatic Arthritis Synovial Inflammation Unique Immunohistologic Features PsA vs RA 1. Significant reduction in monocyte/macrophage cells 2. Synovium exhibits significantly less hyperplasia 3. ICAM-1 and VCAM expression similar, but ELAM lower 4. Synovium more vascular 5. IL-2, IFN-γ, IL-10 present at higher levels than RA 6. IL-1β & TNF-α also present in high levels Ritchlin C et al. Patterns of Cytokine Production in Psoriatic Synovium. J Rheum 1998;25:

ICAM-1 and VCAM expression similar, but ELAM lower 4. Synovium more vascular 5.

PSORIATIC ARTHRITIS Abnormal Bone Remodeling : Role of IL-17 in arthritis TH- 17 fibroblast Inflammation Cytokines : IL-1,6,8 TNF, GM-CSF LIF, GRO, MIP-1α

15 PSORIATIC ARTHRITIS Abnormal Bone Remodeling : Role of IL-17 in arthritis TH- 17 fibroblast Inflammation Cytokines : IL-1,6,8 TNF, GM-CSF LIF, GRO, MIP-1α macrophage Destruction mediators MMP s, NO, COX-2 = CARTILAGE DAMAGE chondrocyte IL-17 BONE EROSION RANKL - Oscteoclastogenesis Koenders et al. Ann Rheum Dis 2006; 65:

macrophage Destruction mediators MMP s, NO, COX-2 = CARTILAGE DAMAGE chondrocyte

16 PSORIATIC ARTHRITIS BONE DESTRUCTION TNFα contributes to joint damage 1 1. Stimulates osteoclast activation (bone resorption) 2. Inhibits osteoblast therefore bone formation 3. Inhibits proteoglycan synthesis = cartilage damage In PsO & PsA high RANKL expression increase signaling osteoclast differeniation 2 1. Bertolini DR, et al. Nature 1986;319: Ritchlin C et al. J Clin Invest 2003;111:1

Inhibits proteoglycan synthesis = cartilage damage In PsO & PsA high RANKL expression increase

17 No definite lab tests Psoriatic Arthritis Diagnosis Common signs & symptoms general fatigue swollen fingers & toes pain & tenderness over tendon insertions morning stiffness (>1 H, >/= 3 mos.) eye redness, photophobia, +/- visual changes nail changes (pitting, onycholysis, hypertrophic)

tendon insertions morning stiffness (>1 H, >/= 3 mos.

18 Psoriatic Arthritis Radiological Aspects Lack of periarticular osteopenia Periostitis (away from joint margin) Bony ankylosis Sacroilitis (unilateral, iliac side) Asymmetic erosions, non-marginal Pencil-in cup deformities & acrolysis Bulky syndesmophytes - spine

Sacroilitis (unilateral, iliac side) Asymmetic erosions,

19 DIP, Pencil-in-cup

20 Unilateral SI

21 Heel Plantar calcification

22 MRI Enthesitis Active

23 Spine Syndesmophytes in PsA 00; 27:1247 Radiology August 2008 vol. 248 no

24 Normal X-ray, + MRI (BME)

25 PSORIATIC ARTHRITIS CASPAR CRITERIA Inflammatory articular disease (joint, spine, or enthesal) AND >/= 3 points of the following 5 categories: CATEGORY DEFINITION POINTS Evidence of Psoriasis : 1 of the following current psoriasis Skin or scalp disease judged by derm or rheumatologist 2 points personal hx of psoriasis Hx obtained from pt., PMD, derm., rheum or other qualified health care provider - FHx of psoriasis Hx in 1 st or 2 nd degree relative by patient report Taylor W, Gladman DD, Helliwell P., et al. Classification Criteria for Psoriatic Arthritis from Large International Study. Arthritis Rheum 2006; 54:2665.

26 PSORIATIC ARTHRITIS CASPAR CRITERIA CATEGORY DEFINITION POINTS Nail Dystrophy RF negative Dactylitis (1 of following) Current dactylitis History of dactylitis X-ray evidence of juxtaarticular new bone formation Onycholysis,pitting,hyperkeratosis on PEx Preferably ELISA not LATEX Swelling of entire digit Hx recorded by rheum Ill-defined ossification near joint margins(exclude osteophyte) on plain films of hand or foot 1 point 1 point 1 point 1 point Taylor, et al. Arthritis Rheum 2006; 54: 2665.

27 GRAPPA PsA Treatment Guidelines Diagnosis Peripheral Arthritis Skin and Nail Disease Axial Disease Dactylitis Enthesitis tis NSAID s IA steroids DMARDs Biologics Topicals PUVA/UVB DMARDs Biologics NSAID s PT Biologics NSAID s Injection Biologics NSAID s Injection Biologics Reassess Response to Therapy and Toxicity

28 Controlled Trials of DMARDs in PsA COMPOUND ARTHRITIS SKIN Sulfasalazine(5) Marginal None Methotrexate(1) Improvement PGA only Improvement Cyclosporin(abs) Marginal Good Gold Marginal None Azathioprine(1) Marginal None Lefluonimide(1) PsARC 59% ACR % PASI(median) 23.8% 1. Palit J. Br J Rheum 1990;29: Clegg DO. Arth Rheum 1996;39: Wilkins Rf. Arth Rheum 1994;27: Spadaro A. Clin Exp Rheum 1995;13: Kaltwasser P. Arth Rheum 2004;50:

29 TNFi PsA Controlled Trials Phase III COMPOUND Duration ACR PASI X-ray Etanercept N= mg BW Infliximab N=200 5 mg/kg Adalimumab N= mg EOW Wk % 23%PASI75 vs 3% pbo Wk % 63% PASI75 vs 2.3 pbo Wk % 59%PASI75 vs 1% pbo 42%PASI90 Modified Sharp 0.03 mean change vs. 1.0 Unit progress in pbo Modified Sharp -0.7 vs. +o.82 in pbo Total Sharp -0.1 vs in pbo 1. Mease P, et al. Lancet 2000;356: Arth Rheum 2004;50: Antoni CE, et al. Ann Rheum Dis 2005; Aug; 64(8): Mease P, et al. Arth Rheum 2004;50:4097.

30 Psoriatic Arthritis TNFi controlled trials COMPOUND ACR20 PASI 75 Golimumab 1 50 mg q mo N = 146 WEEK 24 52% WEEK 24 40% 100 mg q mo N = 146 N= % 58% PBO N = % 3% Certolizumab mg q mo n=135/ n= MG q EOW N=138/N=90 PBO N = 136 WEEK % 23.5% WEEK %

31 ACR Response Criteria ACR 20 requires 20% reduction 1. Tender joint count (78/78) : - includes DIP hands, DIP + PIP of feet 1. Swollen joint count (78/78) Additional 20% reduction in 3 0f 5 following : 1. Patient global 4. Disability 2. Physician global 5. Acute phase reactant 3. Pain Felton DT, et al. ACR Preliminary definition of improvement in RA. Arthitis Rheum 1995; 38:

32 PSORIATIC ARTHRITIS Conclusions PsA affects 1% of the population PsA is associated with considerable morbidity Radiological damage occurs early in the dz course Polyarticualr presentation carries poor prognosis DMARDS in trials have disappointing efficacy TNFi trials show improvement in jt & skin dz., QOL, & radiographic inhibition Early recognition & aggressive treatment improves Clinical & radiographic outcome

Psoriatic Arthritis. Ewa Olech, MD Division of Rheumatology University of Nevada School of Medicine Las Vegas

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