A complex and severe disabling disease Psoriatic Arthritis A complex and severe disabling disease

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 PsA is one of a group of disorders known as the spondyloarthropathies. PsA is a chronic, progressive inflammatory disorder affecting the joints and skin characterized by osteolysis and bony proliferation. C PsA can range from mild and non-destructive in nature to a severely rapid and destructive arthropathy. Radiographic damage can be noted in up to 47% of patients at a median interval of two years despite clinical improvement on standard DMARD therapy. 1Taylor WJ. Curr Opin Rheumatol. 2002;14:98–103. 2Mease P. Curr Opin Rheumatol. 2004;16:366–370. 3Brockbank J, et al. Exp Opin Invest Drugs. 2000;9:1511–1522. 4Kane D, et al. Rheumatology. 2003;42:1460–1468.

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 7% to 42% of patients with Pso will develop arthritis3 Psoriatic Arthritis 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 Juvenile SpA Reactive arthritis Arthritis associated with IBD PsA Undifferentiated SpA (uSpA) Ankylosing spondylitis (AS) #### 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-11 Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 9/108 Golimumab-Specific Deck: Yes 1Rudwaleit 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 RA: Rheumatoid arthritis

Psoriatic Arthritis Psoriatic arthritis is an inflammatory disease, the manifestations of which may include: Inflammatory arthritis which over time typically progresses to involve greater numbers of joints and can result in joint damage in over 40% of patients Psoriasis Diffuse swelling of the fingers and toes known as dactylitis Enthesitis, which is the inflammation of the point of insertion of tendons, ligaments or joint capsules into bone. Shown here is swelling in the ankle region resulting from the inflammation of the Achilles tendon at the point of insertion into the heel. This is a common site of enthesopathy. ACR Slide Collection on the Rheumatic Diseases; 3rd edition. 1994. Data on file, Centocor, Inc.

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 7.2 cases/105 (men 9.1, female 5.4) 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 #### 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-11 Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 9/108 Golimumab-Specific Deck: Yes 1 Alamos et al. J Rheumatol 2008;35:1354-8; 2Wilson 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

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 Signs and symptoms of PsA in include morning stiffness lasting >30 minutes in 50% of patients, nail involvement in up to 90% of patients (as compared to 40% of psoriasis patients). Patients may present with joint deformity and less pain than is usually seen in RA. Dactylitis may be noted in >40% of patients, eye inflammation in 7-33% of cases. Finally, distal extremity swelling with pitting edema has been reported in 20% of patients as the first isolated manifestation of PsA. 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.

Main Features of PsA #### PLEASE DO NOT DELETE CONTENT BELOW THIS LINE ! #### ########## Presentation updated on Wednesday, 4 August, 2010 by GIB1 ########## ########## Presentation updated on Monday, 16 March, 2009 by KAB3 ########## ########### Presentation updated on Wednesday, 4 August, 2010 ########### Author: GIB1 Purpose: Optimize slide decks QA: 04-Aug-10 Review By: 04-Feb-11 Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 10/108 Golimumab-Specific Deck: Yes ########### Presentation 'PsA Optimize_core_18SEP08_WIRE.ppt' created on Thursday, 18 September, 2008 ########### Author: ANDO QC&C: 18-Sep-08 Review By: 18-Mar-09 Medical Review: No Slide: 5/68 *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

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 Enthesopathy (38%)2 #### PLEASE DO NOT DELETE CONTENT BELOW THIS LINE ! #### ########## Presentation updated on Wednesday, 4 August, 2010 by GIB1 ########## ########### Presentation updated on Wednesday, 4 August, 2010 ########### Author: GIB1 Purpose: Optimize slide decks QA: 04-Aug-10 Review By: 04-Feb-11 Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 11/108 Golimumab-Specific Deck: Yes ########### Presentation 'PsA Optimize_core_18SEP08_WIRE.ppt' created on Thursday, 18 September, 2008 ########### Author: ANDO QC&C: 18-Sep-08 Review By: 18-Mar-09 Medical Review: No Slide: 5/68 Nail psoriasis (80%)4, 5 Dactyilitis (48%)3 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 DIP: Distal interphalangeal 8

Comorbidities in PsA Patients Ocular inflammation1 (Iritis/Uveitis/ Episcleritis) Pso patients6-8 Psychosocial burden Reactive depression Higher suicidal ideation Alcoholism IBD2  Metabolic Syndrome3-5 Hyperlipidemia Hypertension Insulin resistent Diabetes Obesity  Higher risk of Cardiovascular disease (CVD) #### PLEASE DO NOT DELETE CONTENT BELOW THIS LINE ! #### ########### Presentation 'OPTIMize_Pso_core_24NOV08.ppt' created on Monday, 24 November, 2008 ########### Author: SILE QC&C: 24-Nov-08 Review By: 24-May-09 Medical Review: Yes Slide: 11/131 ########### Presentation 'OPTIMize_Pso_core_14MAY09.ppt' created on Thursday, 14 May, 2009 ########### Author: SILE QC&C: 14-May-09 Review By: 24-Oct-09 Medical Review: Yes Slide: 1/131 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; 4Neimann 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

Hallmark Clinical Features in PsA 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. Ritchlin C. J Rheumatol. 2006;33:1435–1438. Helliwell PS. J Rheumatol. 2006;33:1439–1441.

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 Dactylitis is characterized by swelling of a digit and may be acute with painful inflammatory changes, or chronic changes where the digit remains swollen despite the disappearance of acute inflammation. Digits with dactylitis are referred to as sausage digits. Dactylitis is recognized as one of the cardinal features of PsA, occurring in up to 40% of patients. Feet are most commonly affected. Dactylitis-involved digits show more radiographic damage. Shown here is psoriasis involving the first, third and fourth toes accompanied by PsA of the interphalangeal joints of the third and fourth toes and dactylitis. The “sausage shape” of these toes is caused by soft-tissue swelling. 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.

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 Entheses are the regions at which a tendon, ligament, or joint capsule attaches to bone. The entheses act to dissipate biomechanical stress and are subjected to repeated microtraumas. Inflammation at the entheses is called enthesitis and is a hallmark feature of PsA. The pathogenesis of enthesitis has yet to be fully elucidated. Isolated peripheral enthesitis may be the only rheumatologic sign of PsA in a subset of patients. 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.

Classification Criteria of PsA How to diagnose PsA? #### 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-11 Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 14/108 Golimumab-Specific Deck: Yes

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 1Moll JMH, Wright V. Psoriatic arthritis. Semin Arthritis Rheum 1973;3:55-78 2Gladman DD et al. Q J Med. 1987;62(238):127-41 3Torre Alonso JC et al. Br J Rheumatol. 1991;30(4):245-50 4Helliwell PS & Taylor WJ, Ann Rheum Dis 2005;64:3-8 5 Gladman et al. Derm therapy 2009;22:40-55 It is important to note that since the original Moll and Wright publication of 1973, the proportion of each subgroup has been changed. The symmetric polyarthritis in the original publication was only 15% and now was shown to be the predominant group. The last 3 bullet points are as in Moll&Wright’s ref. Helliwell & Taylor, ARD, 2005: Fig.1 shows different distributions of Sym. PolyA and Asym. OligoA according to different references. For a recent review on SUBTYPES of PsA, PsA classification and a suggestion for a NEW classification, check out Coates & Helliwell, Clinical Rheumatology, July 2008. Ref 1973 Moll 1987 Gladman 1991 Torre ----------------------------------------------------------------------------------------------------------------------------- DIP <5% DIP involvement found in all groups ----------------------------------------------------------------------------------------------------------------------------- Arth. Mutilans 5% 4% Symmetric Arth. 15% (= PolyA?) 30.5% sym PolyA* 37% OligoA + 36% PolyA No differentiation ------------------------------------------------------------------------------------------------ between symA and Asymmetric Arth. >70% OligoA 28% Asym. OligoA asymA. + MonoA + 30.5% asym PolyA* Ankyl.Arth. 5% 23% SpondA HLA-B27 Not mentioned Not mentioned ########## Presentation updated on Wednesday, 4 August, 2010 by GIB1 ########## ########## Presentation updated on Thursday, 18 September, 2008 by ANDO ########## ########### Presentation updated on Wednesday, 4 August, 2010 ########### Author: GIB1 Purpose: Optimize slide decks QA: 04-Aug-10 Review By: 04-Feb-11 Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 16/108 Golimumab-Specific Deck: Yes associated with SpondA *Torre, 1991, talks about 61% PolyA, with equal repartition of sym.A and asymA.   However patterns may change over time and are therefore not useful for classification 5 HLA: Human leucocytes antigen References see notes

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 #### 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-11 Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 17/108 Golimumab-Specific Deck: Yes McHugh et al. Rheum 2003;42:778-783

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% Juxtaarticular: The prefix "juxta-" comes from the Latin preposition meaning near, nearby, close. #### PLEASE DO NOT DELETE CONTENT BELOW THIS LINE ! #### ########## Presentation updated on Wednesday, 4 August, 2010 by GIB1 ########## ########## Presentation updated on Monday, 16 March, 2009 by KAB3 ########## ########### Presentation updated on Wednesday, 4 August, 2010 ########### Author: GIB1 Purpose: Optimize slide decks QA: 04-Aug-10 Review By: 04-Feb-11 Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 18/108 Golimumab-Specific Deck: Yes ########### Presentation 'PsA Optimize_core_18SEP08_WIRE.ppt' created on Thursday, 18 September, 2008 ########### Author: ANDO QC&C: 18-Sep-08 Review By: 18-Mar-09 Medical Review: No Slide: 7/68 Taylor et al. Arthritis & Rheum 2006;54: 2665-73 16

Spondyloarthritis and Classification Criteria Spondyloarthropathies Axial and Peripheral AMOR criteria (1990) ESSG criteria (1991) Axial Spondyloarthritis ASAS classification 2009 Peripheral Spondyloarthritis ASAS classification 2010 Ankylosing spondylitis Prototype of axial spondylitidis Modified New York criteria 1984 Infliximab (IFX) and Golimumab (GLM) indications #### 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-11 Review Type: Scientific, Reference Check, Compliance Review and HCC Office Slide: 15/108 Golimumab-Specific Deck: Yes Psoriatic arthritis From Moll & Wright 1973 to CASPAR criteria 2006 ESSG: European Spondyloarthropathy Study Group ASAS: Assessment of Spondyloarthritis International Society CASPAR: Classification criteria for psoriatic arthritis Sieper et al. Ann Rheum Dis 2009;68:ii1-ii44 Taylor et al. Arthritis & Rheum 2006;54:2665-73 Van der Heijde et al. Ann Rheum Dis 2011;70:905-8

Outcomes measurements Treatment of PsA Outcomes measurements

Clegg D.O. et al. Arthritis Rheum 1996;39:2013. Outcome Measure in PsA Psoriatic Arthritis Response Criteria (PsARC) Clinical assessment of joint improvement, no skin assessment Improvement in at least 2 of 4 criteria, one of which must be tender or swollen-joint score Physician global assessment (> 1 unit) Patient global assessment (> 1 unit) Tender-joint score (> 30%) Swollen-joint score (> 30%) No worsening in any criterion ACR response slide included in RA presentation Clegg D.O. et al. Arthritis Rheum 1996;39:2013.