Review articleHong Kong Bull Rheum Dis 2008;8:1-11

Psoriatic Arthritis: An Update on Classification, Clinical Featuresand Therapies

Ying-Ying Leung, Lai-Shan Tam, Emily Wai-Lin Kun, Edmund Kwok-Ming Li

DEPARTMENT OF MEDICINE & GERIATRICS, TAI PO HOSPITAL,9 CHEUNG ON ROAD, TAI PO, N.T., HONG KONG SARYing-Ying Leung FHKAM

Emily Wai-Lin Kun FHKAM

DEPARTMENT OF MEDICINE & THERAPEUTICS, PRINCE OF WALES

HOSPITA, THE CHINESE UNIVERSITY OF HONG KONG, SHATIN, N.T.,HONG KONG SARLai-Shan Tam MD

Edmund Kwok-Ming Li MD

Correspondence to: Ying-Ying Leung

Abstract: Psoriatic arthritis (PsA) is a chronic systemic inflammatory disease characterized by joint inflammationand cutaneous psoriasis. With advances in knowledge of genetics, immunohistology and pathogenesis,PsA is now recognized as a distinct disease entity. Unique clinical features include distal interphalangealjoint (DIPJ) involvement, dactylitis, enthesitis, axial involvement, specific radiographic features, and specificskin and nail changes. PsA affects young adults and is progressive and destructive, causing deformities,impaired physical function, reduced quality of life and lost of productivity. We now focus on more aggressivetreatment in patients with progressive disease. With both conventional disease modifying anti-rheumaticdrugs (DMARDs) and emerging biological agents, the outlook for patients with PsA has improved.

Keywords: Classification, Diagnosis, Drug therapy, Epidemiology, Pathology, Psoriatic arthritis

Introduction

Psoriatic arthritis (PsA) is a chronic inflammatory arthritisoccurring in individuals with psoriasis. Both the joint and skinlesions have deleterious effect on affected individuals causingimpaired physical function and quality of life.1 Distinctionbetween PsA and rheumatoid arthritis (RA) is now recognizedclinically, genetically and immunohistologically. The keypathophysiology and cellular processes are being elucidated.Along with advances in the development of a number oftargeted biological therapies, substantial progress in thetargeted therapies has been made. The clinical profile of 127PsA patients in Hong Kong has been described.2 The mean

age of onset was in the third decade. Men and women wereequally affected. Predominant axial disease occurred in 11%and over 70% of patients were treated with disease modifyinganti-rheumatic drugs (DMARDs). Impairment in physicalfunction and quality of life was prominent and 33% of patientsreported loss of employment due to the disease.

Classification

Historically, the Moll and Wright criteria have been used toclassify PsA.3 PsA can be classified when a patient withpsoriasis has inflammatory arthritis and negative rheumatoidfactor. Under these criteria, five subgroups were described:1) asymmetrical oligoarthirits (<5 joints), 2) symmetricalpolyarthritis, 3) distal interphalangeal joint (DIPJ)predominant, 4) spondylitis predominant, and 5) arthritismutilans. Considerable overlaps between subgroups have beenrecognized, and asymmetrical oligoarthritis and symmetricalpolyarthritis was noted to be changing with time and withtreatment.4,5 Some authors advocated classification into twobroad subgroups: peripheral disease (PD) and axial disease(AD).6 The Classification of Psoriatic Arthritis study group(CASPAR) criteria were recently developed as a agreed andvalidated classification for PsA.7 They give a sensitivity andspecificity of 0.914 and 0.987 to classify PsA from otherarthropathies (Table 1).

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Clinical Manifestations

PsA is classified as subtype of spondyloarthropathy based oncommon HLA association and characteristic clinical andimmunopathological features. As compared to RA, PsA hasgreater tendency towards asymmetry and oligoarticularinvolvement. The DIPJs are more frequently involved. SevereDIPJ involvement and digital tuft resorption could give riseto telescoping of finger or arthritis mutilans. Enthesitis anddactylitis are more common. Rheumatoid factor, which isdetected in 80% of patients with RA, may only present in 3%of PsA. Rheumatoid nodules are typically absent in PsA.1

SpondylitisPsA is classified as a subtype of spondyloarthopathy basedon common HLA association and characteristic inflammatoryclinical and immunopathological features. The prevalence ofaxial disease varies from 25% to 70% depending on the criteriaused.8,9 High prevalence of asymptomatic radiologicalsacroiliitis and spondylitis have been reported.2,10-12 Thedistribution of sacroiliitis and syndesmophytes tends to beasymmetrical. The occurrence of extraarticular manifestationis common, including mucous membrane lesion, iritis, andurethritis. The association with HLA-B27 however is onlyweak. The prevalence of HLA-B27 was only around 20% invarious cohort. It had no associated with MRI sacroiliitis11 anddid not influence disease progression in long term follow up.13

The Presence of Skin PsoriasisThe presence of psoriasis is the most distinguished feature ofPsA. Psoriasis is an itchy skin lesion characterized by well-demarcated erythematous and scaly plaques, distributed overextensor body surfaces and scalp. Psoriasis is of two maintypes: psoriasis vulgaris (plaque psoriasis) and pustular

psoriasis. Different types of psoriasis can be divided intosubgroups according to severity, location on body andmorphological appearance of the lesion. Psoriasis usuallyprecedes arthritis in 70% of patients and occurs concomitantlyin 15%. Arthritis however, may precede psoriasis in 15% ofcases and make diagnosis of PsA difficult.14 In the Hong Kongcohort, psoriasis preceded PsA in 60.4% of the patients by5.4 (± 4.8) years. Psoriasis occurred concurrently with PsA in18.9%; psoriasis occurred after arthritis in 20.7%.2

Psoriasis may also present in 'hidden' sites like around theumbilicus, under the hairline, or even natal cleft. Psoriasismay only be evident in the nails. Nail dystrophies includespitting, subungual hyperkeratosis, discoloration andonycholysis. The association of nail lesions with DIPJ waswell recognized.15 PsA is associated with higher rate of naildystrophy than psoriasis alone. One study reported nail lesionsin 40-45% of patients with psoriasis and up to 80% of patientswith PsA.16 In true absence of psoriasis, positive family historyin the first-degree relative might be of equal importance.

The course of psoriasis is influenced by various environmentalfactors. Many patients experience worsening of symptomswith weather change. The classical Koebner's phenomenonwhich describe the worsening of psoriasis lesion at site ofphysical injury, is possibly mediated through the unmaskingof autoantigens and release of proinflammatory cytokines.17

Infection like streptococcal infections and humanimmunodeficiency virus infection have long been recognizedas triggers for psoriasis.18,19

DactylitisDactylitis is one of the hallmarks of PsA. It occurs in onethird of patients with PsA. It appears as swelling and sausaging

Table 1. The Classification of Psoriatic Arthritis (CASPAR) criteria for classification of PsA7

Inflammatory articular disease (joint, spine or entheseal)

With 3 or more points from the following:1. Current psoriasis (sores 2 points)

2. Personal history of psoriasis (if current psoriasis not present)

3. Family history of psoriasis (if personal history of psoriasis or current psoriasis not present)

4. Psoriatic nail dystrophy

5. A negative test for rheumatoid factor

6. Current dactylitis

7. History of dactylitis (if current dactylitis not present)

8. Radiological evidence of juxta-articular new bone formation

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of the entire digit. Predominant flexor tenosynovitis wasdemonstrated in magnetic resonance imaging (MRI) andultrasonography studies.20,21 Dactylitis may also extend beyondthe digits to involve other structures like the palmer tendonsheath and bursa.22,23 Soft tissue edema was also a commonfeature. Acute dactylitis is a marker of active disease of PsA.It was shown to be associated with a greater degree ofradiological damage than digits without dactylitis.24

EnthesitisEnthesitis is the inflammation at the site of attachment of atendon or ligament to the joint capsule. With the emergingknowledge from anatomical and MRI studies, the concept of"enthesis organ" has emerged.25 In this concept, the enthesisand its adjacent fibrocartilage, periosteum, synovium shouldbe viewed as an "unique" organ. PsA was proposed to be aprimarily enthesis disease as compared to synovial disease ofRA.26 Clinical features that are supporting this enthesitispathology include peripheral enthesitis, dactylitis, DIPJinvolvement, spinal inflammation, and specific periostitis andosteolysis. For example, the typical "pencil-in-cup" deformityof the DIPJ can be explained by enthesitis. While the DIPJhas too little synovium to be inflamed, the distal tuft exhibitscapsule calcification and central erosion at the site of tendoninsertion. The fluffy periostitis and bone erosion adjacent tothe capsule are also suggestive of enthesitis.

SAPHO SyndromeThe SAPHO syndrome (Synovitis, Acne, Pustulosis,Hyperostosis and Osteitis) was reported in 2% of patients with

PsA.27 The occurrence of musculoskeletal manifestations(including synovitis, chest wall artho-osteitis and multifocalaseptic osteomyelitis) in association with severe acne,palmoplantar pustulosis and psoriasis was also related toinflammatory bowel disease and other spondyloarthopathies.The psoriatic variety is typically HLA-B27 negative.

Specific Radiographical FeaturesThe specific radiographical features of PsA are grouped intoerosion and proliferation.28 Erosions typically begin at the jointmargins and progress towards the center. Erosions can be veryextensive leading to the characteristic pencil-in-cup deformity(Figure 1a) with a blunted osseous surface on the proximalbone, protruding into an expanded surface of the distal bone.Marked osteolysis may occur such that the whole phalanxmay be resorbed (Figure 1b). The DIPJs are often the first tobe affected. Proliferative changes with new bone formationmay occur along the shaft of the bones, causing metacarpalor metatarsal shaft periostitis. Osteoperiostitis of the distalphalanx of big toe is frequent in PsA and is reported to beassociated with nail dystrophy. Typically, osteolysis (erosivechange) and ankylosis (proliferative change) may occur inthe same hand and even the same finger. Joint involvement inPsA is often asymmetrical. A ray pattern involving the samefinger is contrasted with the mirror pattern in RA. Periarticularosteoporosis is less commonly observed than in RA.

Spondylitis may be similar to that of AS. However,unilateral sacroiliitis, asymmetry of syndesmophytes, and

Figure 1. Typical radiographic features of PsA. (a) Pencil-in-cup deformity (black arrow) and distal interphalangeal joint ankylosis (greyarrow) appear on radiography of same hand. (b) Distal phalanx tuft resorption (white arrow) and distal interphalangeal joint ankylosis (grey

arrow) appear on radiography of same hand.

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non-marginal syndesmophytes distinguish PsA from AS.Non-marginal syndesmophytes describes vertebralossification from vertebral body-to-body as compared tothose from corner-to-corner in AS. PsA spondylitis canbe less symptomatic and even asymptomatic.2,10,12

Nonetheless, radiological spinal disease also predictincreased mortality.29

Burden of Disease and Increased Atherosclerosis

PsA typically affects young adults aged 35-55 years. Thespectrum of severity of PsA is broad, ranging from mild degreeof joint pain to severe deformities. PsA is not benign, there issubstantial social and financial implications to the societyincluding impact on medical burden and inability to work.30,31

PsA is well recognized as a cause of progressive joint damage,32,33

increased disability,31,34 impairment of quality of life,35,36 andincreased mortality.29 The commonest cause of death iscardiovascular diseases. The risk of premature death is relatedto previous active and severe joint disease, presence of erosions

and high erythrocyte sedimentation rate at presentation.Interestingly, PsA patients have higher incidence of metabolicsyndrome including obesity, insulin resistance, dyslipidemia,hypertension possibly related to the common inflammatorypathway.37,38 Subclinical atherosclerosis has also been reportedin PsA cohorts.39-41

Outcome Measures

PsA outcome measures have been adapted from that of RA.Many of these measures were shown to be effective inassessment of peripheral joint and skin diseases, physicalfunctioning, quality of life and X-ray structural damages.Methods to evaluate enthesitis, dactylitis and spinalinvolvement are still under development (Table 2). The Groupfor Research and Assessment of Psoriasis and PsoriaticArthritis (GRAPPA) is a consortium of internationalinvestigators. It is involved in developing, refining andvalidating these existing outcome measures as well as thoseunder development.42

Table 2. Psoriatic arthritis outcome measures50,57

Arthritis ResponseACR Response Criteria (including DIPJ and CMCJ)Psoriatic Arthritis Response Criteria (PsARC)Disease Activity Score (DAS)

EthesitisMander Enthesitis Index (MEI)Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)Leeds Enthesitis Index (LEI)

DactylitisDactylitis CountLeeds Dactylitis Index (LDI)

Radiological AssessmentsModified SharpModified van der Heijde

Skin ResponsePsoriasis Area and Severity Index (PASI)Dermatologist Static GlobalPhysician Global Assessment of Psoriasis (PGA)

QoL/ Physical FunctioningMedical Outcome Short Form 36 (SF-36)Health Assessment Questionnaire Disability Index (HAQ-DI)Psoriatic Arthritis Quality of Life (PsAQoL)Dermatology Life Quality Index (DLQI)Dermatology Quality of Life Scale (DQoLs)

5Leung et al

PsA has been the focus of the Outcome Measures inRheumatology Clinical Trials (OMERACT) group in the pastfew years. Consensus has been achieved on a core set of 6domains (peripheral joint activity, skin activity, patient globalassessment, pain assessment, physical functioning, and healthrelated quality of life HRQOL) to be assessed in clinical trials.43

Despite its differences from RA, the adaptation of RAmethodologies in radiological assessment was considered tobe appropriate.44 Given its construct validity and sensitivityto change, there is adequate evidence in using the physicalfunctioning of SF-36 in assessing physical functioning inPsA.45,46 A quality of life instrument specific to PsA(PsAQoL) has been developed recently.47 In addition toHAQ and SF-36, there is consensus to use this PsAQoL infuture treatment trials to test its performance. Researchesare underway aiming at incorporating the World HealthOrganization (WHO)'s International Classification ofFunctioning, Disability and Health (ICF) schema in thedevelopment of a comprehensive questionnaire that morecomprehensively address physical functioning, quality oflife and participation (i.e. the involvement in lifesituations) pertinent to patients with PsA.48

Genetic Basis for PsA

Psoriasis and PsA are complex genetic disorders resulting frominterplay between genetic and environmental factors. Therelative risk for PsA among first-degree relatives indicates astrong genetics association. The human leukocyte antigen(HLA) region on chromosome 6p is implicated as one of thecandidate regions in PsA. Association with HLA-B13, B-17,B-27, B-39, B-39, HLA-Cw6 and HLADRB1*07 has beendemonstrated.49

Immunopathogenesis of PsA

Immunohistology of various spondyloarthropathy subtypesincluding PsA is in synovial biopsy. It is distinct from that ofRA. Angiogenesis is a prominent early event in both psoriasisskin and synovium. TNF-α up-regulates angiogenic growthfactors including vascular endothelial growth factor (VEGF),transforming growth factor beta (TGFβ), platelet-derivedgrowth fac tor and angiopoie t ins . The resul tantneovascularization is an important component of theinflammatory and erosive nature of the disease.50

TNF-α plays a central role in the pathogenesis of PsA andpsoriasis. High levels of TNF-α are found in synovial fluid,synovium, serum and psoriatic skin lesions of patients withPsA. Treatment with TNF-α inhibitors also leads to substantialbenefit. The pathophysiology of PsA is summarized in Figure2. Other key cytokines that are up regulated in PsA, and thusmay be potential therapeutic targets include IL-1, IL-6, IL-12,IL-15, and IL-18. T cell activity is also up regulated andinhibition of T cell via blockage of "co-stimulatory" pathwaymay also be a therapeutic target.

PsA Therapy

Conventional DMARDsA challenge of PsA therapy is to address the multiple domainsof the disease: arthritis, enthesitis, dactylitis, spinal disease,skin disease, physical functioning and quality of life. In milddisease, nonsteroidal anti-inflammatory drugs (NSAIDs) ortopical ointment (e.g. corticosteroid or vitamin D analogues)for skin disease may be appropriate. Moderate to severemanifestation often requires disease modifying anti-rheumaticdrugs (DMARDs) Conventional DMARDs includingmethotrexate, sulphasalazine, leflunomide, anti-malarials andcyclosporin A have proven efficacy in PsA. Comprehensivereviews of therapy of PsA have been published.51,52 In theCASPAR cohort study involving 588 PsA patients across 13countries (mean duration of illness, 12.5 ± 0.4 years),methotrexate was the most frequently used DAMRDs (39%)in which > 70% of patients were still taking the drug. Otherdrugs were used with the following frequencies respectively:sulphasalazine 22%, gold salts 7%, anti-malarials drugs 5%,corticosteroids 10% and anti-TNF drugs 6%.53 A summary ofthese treatment with ratings of level of evidence is outlined inFigure 3.

Methotrexate is effective for both skin and joint disease inPsA. Its efficacy has been demonstrated but in smallrandomized controlled trials.54,55 Its liver toxicity has elicitedconcerns regarding its long-term use. There is an apparentyet unexplained increase in proclivity for hepatotoxicity inpsoriasis patients verse RA patients.56 A discord still existsamong dermatologists and rheumatologists regardingmethotrexate monitoring. The American College ofDermatology recommends pretreatment liver biopsies andrepeat biopsies after 1.5 gram accumulated dose,57 whereasthe American College of Rheumatology (ACR) guidelinerecommends pretreatment liver biopsies only in patients with

6 Psoriatic Arthritis

Figure 2. Pathophysiology of PsA.

persistently elevated liver enzymes, chronic hepatitis B or Cinfection, or significant alcohol intake; and with repeatbiopsies only as indicated by results of liver enzymes.58 In aretrospective study of 104 PsA patients followed over twodecades, there was no suggestion of increased liver toxicity.59

Sulphasalazine has proven efficacy for peripheral arthritis inPsA from several randomized controlled trials.60-62 In thelargest trial that evaluated 221 patients treated withsulphasalazine 2 g/day for 36 weeks, 57.8% of sulphasalazinepatients vs. 44.6% of placebo patients (p=0.05) achieved thePsA Response Criteria (PsARC).62 The efficacy ofsulphasalazine however, is confined to peripheral joints. It isnot effective for axial disease or skin disease.63

Leflunomide is a selective pyrimidine synthesis inhibitortargeting activated T cells lacking a salvage pathway. Its

efficacy in PsA and psoriasis was demonstrated in onerandomized controlled trial in 188 patients with active PsA.More than half of them had been inadequately controlled byother DMARD. After 6 months, 59% of leflunomide-treatedvs. 30% placebo-treated patients achieved the PsARC respond;24% had significant PASI score improvement (compared with0% in placebo group).64 Leflunomide is generally welltolerated, with the commonest adverse event being diarrhea.

The use of anti-malarials is limited by the concern of theirexacerbation of psoriasis skin lesions.65 More frequentreactions were observed in early trials that primarilyused regimens with quinacrine. Chloroquine orhydroxychloroquine seems to have less toxicity. In acase-control study, 6 out of 32 chloroquine-treated patientsexperienced a psoriasis f lare, only one requireddiscontinuation of therapy. There was no case of exfoliative

7Leung et al

Figure 3. GRAPA treatment guideline

for PsA.[Categories of evidence; strength of recommendation]

dermatitis. Six of the 24 control patients had an exacerbationof psoriasis as well. 75% of the chloroquine-treated patients(compared with 58% of control) had a 30% reduction in activejoint inflammation over a 6-month period.66 Prospectivecontrolled trials are required to establish the efficacy and safetyof these agents.

Cyclosporin A has been used with success in psoriasis andPsA. Toxic effects, most notably hypertension and renaltoxicity, limit its use. A prospective controlled trial comparingcyclosporin A (3 mg/kg/day) with methotrexate (7.5 mg/week)for one year has demonstrated equivalent efficacy in 35patients with PsA.67 The efficacy of cyclosporin A withmethotrexate on arthritis and PASI has been demonstrated.68

TNFααααα InhibitorsAnti-TNFα agents, including infliximab, etanercept andadalimumab have shown the greater efficacy over anyconventional DMARDs in various clinical aspect of PsA.They may have minor difference in efficacy in the skinand enthesium, but all have excellent effects in thesedomains.

A phase 3 double blind placebo-controlled trial evaluated theefficacy of 5 mg/kg infliximab in 200 patients with PsAunresponsive to previous treatment (IMPACT 2).69 ACRcriteria and PsARC response were achieved by 58% and 77%of infliximab patients as compared to 11% and 27% of placebopatients at week 14. Fewer infliximab patients than placebo

8 Psoriatic Arthritis

patients had dactylitis (12% vs. 34%; p<0.001) and activeenthesopathy (20% vs. 37%; p = 0.002) at week 24. Significantbeneficial effect to skin lesions was demonstrated, 64% ofinfliximab patients achieved 75% PASI improvement (PASI 75)compared to 2% of placebo patients. A high degree of clinicalresponse in peripheral arthritis, dactylitis, enthesopathy andpsoriasis were maintained at end of 2 years.70 Infliximab wasshown to inhibit radiographic progression. At week 54, thechange of modified Sharp/van der Heijdi score in infliximabpatients were -0.7 ± 2.53 compared to 0.82 ± 2.62 in placebopatients (p<0.001).71 Over 2 years, the average estimatedannual radiographic progression with infliximab treatment wassignificantly reduced versus the estimated baseline rate ofprogression.70 At week 14, a higher proportion of infliximabpatients achieved a minimal clinical change in HAQ score [i.e.more than 0.3 decrease] (59% vs. 19%; p < 0.001). The physicaland mental components of SF-36 scores also improved ininfliximab group.72 Infliximab was well tolerated with similarincidence of adverse events compared to placebo group.

The efficacy of subcutaneous etanercept 25 mg administeredtwice-weekly was demonstrated in a phase 3 randomizedplacebo-controlled trial (n=205).73 ACR 20 response wasachieved in 59% of etanercept patients as compared to 15%of placebo patients at the end of 12 weeks (p<0.001), and theresults were sustained at 24 and 48 weeks. Psoriasis responsewas significant, 23% of etanercept patients achieved PASI 75verse 3% of placebo patients (p<0.001). Radiographicprogression was inhibited in etanercept group at 12 months,the change of modified Sharp score (mTSS) was -0.03 units,compared with +1.00 unit in placebo patients (p=0.001).Sustained respond with arthritis, radiographic damagesuppression, physical function and quality of life weredemonstrated in the extension trail at the end of 2 years.74

The efficacy of adalimumab, given at 40 mg subcutaneousevery other week was studied in a large (n=313) phase 3 study,the Adalimumab Effectiveness in Psoriatic Arthritis Trial(ADEPT).75 At week 12, 58% of adalimumab patients achievedACR20 response compared to 14% of placebo patients(p<0.001). No difference in response rate was noted betweenpatients taking adalimumab alone or in combination withmethotrexate (50% of patients). There were greater meanimprovement in dactylitis and enthesitis in the treatment group,but the results were not statistically significant. PASI 75 wasachieved in 59% of adalimumab patients compared to 1% ofplacebo patients (p<0.01). Radiographic progression asassessed by modified Sharp score was significantly inhibitedin the treatment group. Mean change in HAQ score was

significant and clinically meaningful (-0.4 vs. -0.1; p<0.001).Improvement in SF-36 in the treatment group was noted. Theseclinical response were sustained at end of 2 year with a gooddrug safety profile.76

The Risks and Benefits of TNFα inhibitors in PsA wereevaluated in a metaanalysis. Six randomized controlled trialswith 982 patients were included. All 3 TNFα inhibitors wereshown to be more effective than placebo as measured byPsARC, ACR20, 50 and 70 ratings. There were no importantadded risks associated with their short-term use.77 Spinedisease however, was not studied in these trials. As significantefficacy of TNFα inhibitors has been demonstrated in AS,78

extrapolation of this experience to PsA seems reasonable.Although with limited data, cost effectiveness of TNFαinhibitors in the management of PsA seems promizing.79,80

Other Biologic AgentsAlefacept is a fusion protein that blocks interaction betweenleukocyte-function-associated antigen-3 (LFA-3) on antigenpresenting cells and CD2 on T cells. It binds to CD2 onactivated T cells and impairs the co-stimulatory signalsdelivered by LFA-3 and thus induces apoptosis in circulatingmemory T cells. It efficacy in combination with methotrexatefor both joint and skin diseases was demonstrated in a phase2 trial (n=185). However, its efficacy for joint disease wasvery limited.81

Efalizumab is a humanized monoclonal antibody targeting atCD11 subunit of LFA-1 on T cells. It interferes with T cellcoupling with ICAM-1 on endothelial cells. Activation of Tcells and migration of cells to the site of inflammation is theninhibited. It is approved for use in psoriasis. A phase 2 trial(n=107) failed to demonstrate significant difference in ACR20response as compared to placebo.82 It is therefore notrecommended for treatment of arthritis.

Abatacept (CTLA4-Ig) is a recombinant fusion proteinbinding to the CD80/86 receptor on antigen presenting cells.It blocks the second-signal activation of CD28 on T cells. Ithas been approved for use in RA. A phase 2 trial for use inpsoriasis has been conducted.83 It may have beneficial effectson peripheral arthritis in PsA.

Conclusion

PsA is a chronic systemic inflammatory disease involving skin,peripheral joints, spine and enthesis. It affects young adults

9Leung et al

and is progressive and destructive, causing deformities,impaired functional status and quality of life. It is nowrecognized as a distinct disease entity clinically,radiographically, genetically, immunohistologically and hasunique pathogenesis. Numerous studies have increased ourunderstanding of pathophysiology of PsA, which providedsupport for targeted therapy. The effectiveness of these agentshas also helped to elucidate the pathogenesis of PsA andpsoriasis, which may lead to more novel and effective targetedtherapies. Anti-TNF therapy has achieved encouragingefficacy in alleviating skin and joint disease and variousdomain. The benefit of anti-TNF therapy should be balancedagainst the adverse events and cost. The risk of seriousinfection, in particular tuberculosis is a definite challenge inSoutheast Asian countries. Further comprehensive and longterm health economic analyses are required to aid our abilityto see the full impact of these new targeted therapies on patientfunction, quality of life, employment and productivity in thecontext of the society.

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