1 PSORIATIC ARTHRITIS PSA AND OUTCOME MEASURES
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by arthritis associated with skin psoriasis and several extra articular manifestations. The clinical complexity of this disease is mirrored in the difficulties of its assessment, which ranges from peripheral and axial arthritis to enthesitis, dactylitis, skin and nails lesions, and patient perception of disease (i.e. fatigue, pain, quality of life, functional and global status) This paper summarizes the main assessment tools available for PsA in clinical practice and research trials. Revista Latinoamericana de Psoriasis y Artritis Psoriasica 2012, 5: 1 10 http:/www.fmv uba.org.ar/ Assessment in Psoriatic Arthritis 2 Psoriatic Arthritis (PsA) is a systemic inflammatory disease characterized by the prominent involvement of the peripheral and axial joint and by skin dermatitis (psoriasis, Ps) It is usually seronegative for rheumatoid factor and also for this reason has been included in the spectrum of the spondyloarthropaties which share this condition (SpA) According to the classical Moll and Wright classification (1) PsA may present different clinical pictures: peripheral joint arthritis (oligoarticular, polyarticular, distal or mutilans pattern) or inflammatory spinal disease. Overlap of clinical subtypes is common. Other clinical manifestations that deeply influence the clinical picture are: enthesitis, dactylitis, tendonitis, uveitis, features that are common to the other spondyloarthropathies such as ankylosing spondilitis (AS) reactive arthritis (ReA) and SpA associated with inflammatory bowel disease (IBD) (2) The early immunological events in PsA pathogenesis are considered to take place largely on the basis of a genetic susceptibility (3, and to be mediated by T cells (4) interacting with other cells (5) giving rise to the inflammatory cascade which then activate a wide range of pathways, leading ultimately to joint damage and repair mechanisms. Recently, increasing evidence has underlined the role of a new subset of T lymphocyte, named Th17 according to its signature cytokine, to the pathogenesis of PsA. It is noteworthy that when PsA patients present spinal involvement they often are positive for the HLA B27 marker (6) Clinical monitoring and assessment of response to drug treatment were influenced in the past by the lack of specific outcome measures for treatment. The need to test the efficacy and safety of new biologic agents in randomized controlled trials was the main force to trigger a collaborative effort to define domains and develop instruments which could effectively assess response to treatment. Furthermore new classification criteria were developed by the international multicentre (30 rheumatologists) CASPAR group (Classification of Psoriatic Arthritis) to differentiate PsA from other forms of arthritis (7) In the last decade several Rheumatologist, Dermatologists and non clinical members joined in GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) with the aim to validate and standardize outcome assessment tools in PsA and Ps, both for clinical practice and for therapeutic investigative studies. Key domains for assessment of disease activity and response to treatment in PsA and Ps were identified through a multi step process by means of literature review (8) and a Delphi exercise (9) Further work took place during the first GRAPPA meetings and OMERACT modules in Asilomar (CA) (10) and Malta (11 12) Six domains were included in the inner circle of the core set of recommended domains to be assessed in randomized controlled trials and/or longitudinal observational studies in PsA. Eight domains were also considered important but not mandatory and were included in the outer circle. Five domains did not receive sufficient support for inclusion in the core set but were considered important and were placed in the research agenda (Table 1) Following this first stage GRAPPA set up committees to study old e new instruments to measure these domains. In this paper we review the assessment of the principal domains and the instruments useful in daily clinical practice and in research studies. Assessment of peripheral joint Several instruments have been applied in drug trials to point out treatment efficacy compared to placebo. Among these instruments the most popular are: the American College of Rheumatology (ACR) response criteria developed in patients with rheumatoid arthritis (RA) (13) and the Psoriatic Arthritis Response Criteria (PsARC) developed in patients with PsA for a trial testing sulfasalazine efficacy in PsA (14) These criteria include clinical assessment of swollen Revista Latinoamericana de Psoriasis y Artritis Psoriasica 2012, 5: 1 10 http:/www.fmv uba.org.ar/ Assessment in Psoriatic Arthritis 3 joint count (SJC) tender joint count (TJC) patient and physician self assessments of global disease activity. To satisfy the ACR20 (or 50 or 70) response criteria the patient must shows improvement =20% (or =50% or =70% in both the swollen and tender joint counts, as well as a 20% (or =50% or =70% improvement in 3 of the following 5 items: patient and physician global assessments of disease activity (by means of visual analogue scale, VAS) patient pain evaluated by means of VAS (0 100) Health Assessment Questionnaire (HAQ) and either erythrocytes sedimentation rate (ESR) or C reactive protein (CRP) The PsARC measures swollen joint scores (SJS) tender joint scores (TJS) patient global assessment (on a 0 5 point scale) and physician global assessment of disease activity (on a 0 5 point Likert scale) A response is detected by a reduction of 30% in SJS and or TJS and reduction of at least 1 unit in Likert assessment scores. The overall response is fulfilled when improvement is present in 2 of the 4 items (one must be SJS or TJS) without worsening in any domain. Another instrument that has been proposed and applied in peripheral subset PsA is the DAS composite score which includes 44 SJC and TJC, or the simplified DAS28, a 28 tender and swollen joint count plus patient global assessment of well being and ESR or CRP (15) The DAS defines arthritis disease activity at time of visit, EULAR DAS response criteria consider the change from two distinct time points. Application of the DAS28 to PsA is not encouraged because of the limited number of joints evaluated. In clinical evaluation of PsA patients it is suggested to use the 68 joint count because it includes the majority of joints affected in PsA. Recently, Philip Helliwell from Leeds University promoted a collaborative multi centre study (GRACE) addressing the issue of development of a new comprehensive disease severity and responder composite index for Psoriatic Arthritis (PsA) (16) work is still in progress. Assessment of skin Skin psoriasis is a major manifestation of disease in PsA, it is responsible of discomfort and may cause low quality of life. It is therefore important to evaluate skin involvement precisely and objectively. There are basically two approaches, one is subjective: patient and/or physician global assessment of disease activity and the other objective, photographs and or calculation of involved and severity of body surface area. Specific tools include Psoriasis Area Severity Index (PASI) (17) Lattice System Physician Global Assessment (LS PGA) (18) and National Psoriasis Foundation Psoriasis Score (NPF PS) (19) Despite the known deficiencies of PASI score, mainly low performances in patients with low degree and extent of skin psoriasis, PASI has functioned well in randomized clinical trial testing the efficacy of new biologic drugs in both in psoriasis and in PsA. Although it has limitations, PASI still remains the "gold standard" Patient Global Assessment of Disease Activity Patient global assessment (PGA) has been included in inner circle of the core set of domains for the assessment of PsA by GRAPPA and OMERACT (12) Patient global assessment is useful and important because helps physicians to evaluate patient discomfort and to calibrate a more patient centered clinical and therapeutic approach. PGA has also been included in widely used composite indices developed for rheumatoid arthritis but also employed in PsA. Among these measures are the American College of Rheumatology (ACR) response criteria (13) the Disease Activity Score (DAS) (15) and the Psoriatic Arthritis Response Criteria (PsARC) (14) A collaborative study performed on patients enrolled in 18 centres from 10 countries worldwide assessed the reliability of the PGA, measured by means of 0 100 mm visual analogue scale (VAS) and the possible additional utility of separate VAS scales for joints and skin (20) The 100 mm VAS instrument was selected by GRAPPA for this domain, over a 5 point Likert and 11Revista Latinoamericana de Psoriasis y Artritis Psoriasica 2012, 5: 1 10 http:/www.fmv uba.org.ar/ Assessment in Psoriatic Arthritis 4 point numeric rating scales, because of its performance in RA and OA (21, 22) Reliability was determined by test retest. It should be underlined that patient perception of joint disease and patient perception of skin disease explained nearly all the variance in PGA (r squared of 0.73) The study also showed a major impact of the arthritis symptoms over the skin, which was expected given the low PASI scores found in the majority of the patients attending rheumatology clinics, and broadly speaking in the PsA population in general. The possibility that anxiety and depression could substantially affect the perception of the disease by the patients was evaluated and the results suggest that the PsA patients perception was unrelated with the mood status. Therefore the study demonstrated that PGA assessed by means of VAS is a reliable tool related to both joint and skin disease activity. Nevertheless, since joint and skin disease often diverge, it was suggested that both joint and skin should also be assessed