destruction. Apart from its tropism for exocrine glands, the inßammatory process can, however, affect any organ. As a result, clinical features can be divided into two facets: (i) benign subjective but disabling manifestations such as dryness, articular and muscular pain, and fatigue, affecting almost all patients and (ii) systemic manifestations such as synovitis, vasculitis, skin, lung, renal and neurological involvement, or lymphoma. Systemic involvement of the disease, which refers to active inßammatory disease with potential severity, affects 20Ð40% of patients.

Until recently, evidence-based therapy for SjšgrenÕs syndrome was largely limited to treatments that may improve sicca features [1]. Consequently, for decades, the evaluation of primary SS in clinical trials has been primarily based on the assessment of glandular features, either with objective or subjective parameter [2Ð4]. Moreover, all these studies used a different measurement tool, which makes comparisons impossible. Outcome criteria using composite criteria have also been proposed in the most recent clinical trials [5, 6]. But, none of these measures was able to capture the activity of systemic features of the disease, and, until now, therapeutic evaluation of primary SS has never focused on systemic features, despite their potential severity.

Over the past few years, evidence-based evaluation of therapies has become important, with an increasing number of large clinical trials conducted in this disease [1Ð6]. Valid activity indexes were needed [7Ð9] to assess the effectiveness of new targeted therapies, such as B-cell-targeted therapies that have shown promising results for both severe systemic [10, 11] and glandular features [12Ð16]. Therefore, in the past decade, great efforts have been made to determine a core set of outcome measure [7, 8]. The primary SS core set includes sicca features (oral and ocular, subjective and objective), fatigue, health-related quality of life, composite activity score, and laboratory measures. However, assessing the beneÞt of therapies for primary SS lacks consensual outcome measures.

Different disease-speciÞc indexes have then been developed, Þrst, for evaluation of patientsÕ

symptoms (subjective features), such as ProÞle of Fatigue and Discomfort (PROFAD) and Sicca Symptoms Inventory (SSI) [17, 18], and, more recently, for systemic features, such as Ss Disease Activity Index (SSDAI) [19] and SjšgrenÕs Systemic Clinical Activity Index (SCAI) [20]. The development of these indexes was based on exploratory studies conducted in a single country, but served as bases of the present collaborative project. Thus, EULAR has promoted an international collaboration between primary SS experts to develop consensus disease activity indexes. Two indexes have been developed: (i) a patient-administered questionnaire to assess subjective features, the EULAR SjšgrenÕs Syndrome Patients Reported Index (ESSPRI), and (ii) a systemic activity index to assess systemic complications, the EULAR SjšgrenÕs Syndrome Disease Activity Index (ESSDAI).

30.2Evaluation of Systemic Features of Primary SS

As previously mentioned, three disease activity scores have been recently developed to assess activity in patients with systemic complication of primary SS. Table 30.1 compared these three scores.

30.2.1The SSDAI: Sjögren’s Syndrome Disease Activity Index

The SSDAI [19] is a disease activity index that includes 11 items grouped in 8 domains. The weights of each item were obtained with multivariate model using PhGA as gold standard, in a cohort of 206 patients. The relative weightings of each domain are indicated in brackets: pleuropulmonary (4), articular (2), change in vasculitis (3), lymph node/spleen enlargement (2), active renal (2), constitutional (3), change in salivary gland swelling (3), recent onset peripheral neuropathy (1), and leukopenia (1). The Þnal score, the sum of all items, varies from 0 to 21.

Table 30.1 Description of disease activity indexes for primary SjogrenÕs syndrome

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30.2.2The SCAI: Sjögren’s Systemic Clinical Activity Index

The SCAI is an ordinal transition scale, derived from the British Isles Lupus Activity Group (BILAG) scoring system, developed in a cohort of 104 patients [20, 21]. It reßects changes in clinical symptoms during the 4-week period prior to evaluation or compared to the previous visit. SCAI includes 42 items that are clearly deÞned and grouped into the 8 following domains: constitutional, musculoskeletal, skin/vasculitis, respiratory, neurological, renal, salivary gland, and hematological. Each item is scored as absent, improving, the same, worse, or new. This scoring is used to score each domain with an Òintention to treatÓ alphabetical scoring system. Category A denotes disease that requires prednisolone >20 mg and/or immunosuppressants for treatment. Category B denotes disease requires prednisolone <20 mg and/or anti-malarials and/or NSAIDs. Category C indicates stable, mild disease. Category D is assigned to a domain that was previously affected, but where disease is currently inactive. Category E indicates an organ system that has never been involved. Categories were derived from the BILAG index for systemic lupus (created by nominal consensus techniques). This scoring could be converted into a numeric variable according to the author recommendation a A score = 9, a B score = 3, a C score = 1, and a D or E score = 0. Therefore the maximum theoretical SCAI score is 72. This numerical conversion has never been evaluated.

30.2.3The ESSDAI: EULAR Sjögren’s Syndrome Disease Activity Index

The ESSDAI (Table 30.2) is a disease activity index that was generated in 2009, by consensus of a large group of worldwide experts from European and North American countries. The ESSDAI is a systemic disease activity index and includes 12 domains (i.e., organ systems). Each domain is divided in three to four levels

depending on their degree of activity. The weights of each domain were obtained with multiple regression modeling using the physician global assessment of disease activity (PhGA) as gold standard, in a cohort of 702 clinical vignettes based on 96 real patients. The relative weightings of each domain are indicated in brackets: constitutional (3), articular (2), cutaneous (3), glandular (2), lymphadenopathy (4), pulmonary (5), renal (5), muscular (6), peripheral nervous system (5), central nervous system (5), hematological (2), and biological (1). Before rating the score, experts are asked to rate only manifestations related to the disease and to avoid rating long-lasting clinical features. No item is rated as new or worse. The Þnal score, the sum of all weighted scores, falls between 0 and, theoretically, 123, with 0 being the less disease activity.

30.2.4Comparisons of Systemic Disease Activity Scores

In a recent study, we evaluated and compared sensitivity to change of disease activity indexes for primary SS [22]. In this study we included 96 proÞles, were abstracted from real pSS patientsÕ medical charts. Patient proÞles were scored according the 3 scoring systems at 3 consecutive visits by 39 experts. In addition, experts also assessed proÞles according to whether disease activity had improved, worsened, or remained stable at follow-up visits. In this study we showed that, compared to SCAI and SSDAI, the ESSDAI was the most correlated with PhGA of disease activity. Also, when assessing sensitivity to change we found that for patients whose disease activity had improved, all disease activity scores showed a similar large sensitivity to change. But, the ESSDAI adequately varied according to the degree and the direction of change in disease activity, and therefore detects changes more accurately than did the SSDAI and SCAI. Notably, for patients with stable disease activity, the ESSDAI scores did not show erroneous improvement contrarily on SSDAI and SCAI.

Table 30.2 The EULAR SjšgrenÕs Syndrome Disease Activity Index (ESSDAI): domain and item deÞnitions and weights

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Table 30.2 (continued)

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