The Italian Society for Rheumatology recommendations for the management of axial spondyloarthritis.

Over the last few years, the landscape of treatments for axial spondyloarthritis (SpA) has been rapidly evolving, urging international scientific societies to draft or update existing clinical practice guidelines (CPGs) on the management of axial SpA. The Italian Society for Rheumatology (SIR) committed to provide revised and adapted evidence- and expert-based recommendations for the management of patients with axial SpA in Italy. A systematic approach to the adaptation of existing CPGs - the ADAPTE methodology - was adopted to obtain updated recommendations suitable for the Italian context. A systematic literature search was performed in Medline and Embase databases to find international CPGs and consensus statements with recommendations for the management of axial SpA published in the previous five years. A working group composed of rheumatologists with proven experience in the management of axial SpA and methodologists identified the key research questions which guided study selection and data extraction. Guideline quality was assessed using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The Italian recommendations were developed by endorsing or adapting and rewording some existing recommendations. The draft of the recommendations was sent to a multidisciplinary group of external reviewers for comment and rating. Six original CPGs were selected and used to create this SIR CPG, which includes a final set of 14 recommendations covering the management of patients with axial SpA across the following domains: assessment, pharmacological and non-pharmacological treatment, and follow-up. The dissemination and implementation of these SIR recommendations are expected to support an evidencebased clinical approach to the management of patients with axial SpA in Italy.

Consensus on the management of patients with psoriatic arthritis in a dermatology setting.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis (PsO). Early diagnosis and prompt therapeutic intervention are crucial for limiting PsA progression and prevention of disability. Dermatologists are in a privileged position to detect early PsA. The management of patients with PsA in the dermatology setting is widely variable. OBJECTIVE: To provide practical recommendations for the management of patients with PsA in the dermatology setting including early diagnosis and treatment. METHODS: A consensus document was written by an expert panel composed by dermatologists (n = 12) and rheumatologists (n = 6). Eleven highly relevant questions were selected and elaborated with answers/statements based on a narrative literature review. The resulting document was discussed in a face-to-face meeting adopting a nominal group technique to reach consensus (i.e. 100% agreement) using the Delphi method. RESULTS: A consensus was achieved in defining the following: the clinical characteristics differentiating inflammatory and non-inflammatory signs and symptoms of joint disease; the most important differential diagnoses of PsA in clinical practice; the most useful screening questionnaires, serum laboratory tests and imaging techniques for the detection of early PsA; the criteria for dermatologist to refer patients with PsO to rheumatologist; the criteria for the diagnosis of PsA; the selection of the indices that the dermatologist could use for measuring the activity and severity of PsA in clinical practice; when systemic steroids and/or intra-articular steroid injections are indicated in the treatment of PsA. Finally, systemic treatments including synthetic and biologic disease-modifying antirheumatic drugs to be considered for the treatment of PsA have been reported. CONCLUSIONS: The implementations of these practical recommendations could be very helpful for the management of patients with PsA in the dermatology setting including early diagnosis and treatment.

Evidence-based algorithm for diagnosis and assessment in psoriatic arthritis: results by Italian DElphi in psoriatic Arthritis (IDEA).

Psoriatic arthritis (PsA) is a chronic inflammatory disease involving skin, peripheral joints, entheses, and axial skeleton. The disease is frequently associated with extrarticular manifestations (EAMs) and comorbidities. In order to create a protocol for PsA diagnosis and global assessment of patients with an algorithm based on anamnestic, clinical, laboratory and imaging procedures, we established a DElphi study on a national scale, named Italian DElphi in psoriatic Arthritis (IDEA). After a literature search, a Delphi poll, involving 52 rheumatologists, was performed. On the basis of the literature search, 202 potential items were identified. The steering committee planned at least two Delphi rounds. In the first Delphi round, the experts judged each of the 202 items using a score ranging from 1 to 9 based on its increasing clinical relevance. The questions posed to experts were How relevant is this procedure/observation/sign/symptom for assessment of a psoriatic arthritis patient? Proposals of additional items, not included in the questionnaire, were also encouraged. The results of the poll were discussed by the Steering Committee, which evaluated the necessity for removing selected procedures or adding additional ones, according to criteria of clinical appropriateness and sustainability. A total of 43 recommended diagnosis and assessment procedures, recognized as items, were derived by combination of the Delphi survey and two National Expert Meetings, and grouped in different areas. Favourable opinion was reached in 100% of cases for several aspects covering the following areas: medical (familial and personal) history, physical evaluation, imaging tool, second level laboratory tests, disease activity measurement and extrarticular manifestations. After performing PsA diagnosis, identification of specific disease activity scores and clinimetric approaches were suggested for assessing the different clinical subsets. Further, results showed the need for investigation on the presence of several EAMs and risk factors. In the context of any area, a rank was assigned for each item by Expert Committee members, in order to create the logical sequence of the algorithm. The final list of recommended diagnosis and assessment procedures, by the Delphi survey and the two National Expert Meetings, was also reported as an algorithm. This study shows results obtained by the combination of a DElphi survey of a group of Italian rheumatologists and two National Expert Meetings, created with the aim of establishing a clinical procedure and algorithm for the diagnosis and the assessment of PsA patients. In order to find accurate and practical diagnostic and assessment items in clinical practice, we have focused our attention on evaluating the different PsA domains. Hence, we conceived the IDEA algorithm in order to address PsA diagnosis and assessment in the context of daily clinical practice. The IDEA algorithm might eventually lead to a multidimensional approach and could represent a useful and practical tool for addressing diagnosis and for assessing the disease appropriately. However, the elaborated algorithm needs to be further investigated in daily practice, for evidencing and proving its eventual efficacy in detecting and staging PsA and its heterogeneous spectrum appropriately.

Predictive factors for partial remission according to the Ankylosing Spondylitis Assessment Study working group in patients with ankylosing spondylitis treated with anti-TNFα drugs.

The objective of this study was to evaluate the predictive factors for achieving partial remission (PR) in patients with ankylosing spondylitis (AS) treated with anti-TNFα. We longitudinally enrolled in a multi-center study 214 AS patients, classified according to New York criteria, treated with anti-TNFα drugs adalimumab (ADA), etanercept (ETA) and infliximab (INF) with at least 12 months of follow up. PR was reached when the score was <20 mm (on a visual analogue scale of 0-100 mm) in each of the following 4 domains: 1) patient global assessment (in the last week); 2) pain (spinal pain); 3) function [measured by the bath ankylosing spondylitis functional index (BASFI)]; 4) inflammation [mean of intensity and duration of morning stiffness, from the bath ankylosing spondylitis disease activity index (BASDAI)]. Two hundred fourteen AS patients (M/F=160/54; median age/range=43.2/19-78 years; median disease duration/ range=96/36-189 months) were treated with ADA (15.8%), ETA (28.9%) and INF (55.1%). At 12 and 24 months, high serum level of C reactive protein (CRP) (≥2 vs ≤0.8 mg/dL) were associated with higher rate of PR in AS patients treated with anti-TNFα drugs. At 24 months, PR was associated with shorter disease duration (≤36 vs ≥189 months) and higher erythrosedimentation rate (ESR) values (≥45 vs ≤17 mm/h). In male patients lower bath ankylosing spondylitis metrology index (BASMI) (≤2 vs ≥6) and absence of psoriasis were associated with higher PR rate only at 12 months. Other parameters assessed before treatment, such as BASDAI, BASFI, peripheral arthritis, inflammatory bowel disease and uveitis were not associated with PR. Our long-term longitudinal study in a setting of clinical practice showed that inflammatory parameters (i.e. CRP, ESR) and disease duration represent the most important predictive variables to achieve PR with an anti-TNFα treatment.

The role of tumour necrosis factor in the pathogenesis of immune-mediated diseases.

Immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthropathies, Crohn's disease, ulcerative colitis and juvenile idiopathic arthritis, comprise a group of chronic disorders characterized by an immune-mediated pathogenesis. Although at clinical presentation these diseases appear unrelated, they have been recognized to share similar pathogenic mechanisms. Data from epidemiological and genetic studies further support the concept that IMIDs are interrelated, as they can co-occur in the same patient and share a similar genetic susceptibility. The specific aetiologies of IMIDs remain unknown, but all are known to involve dysregulation of the immune system, including an over-expression of the pro-inflammatory cytokine tumour necrosis factor (TNF). The pivotal role played by TNF in the pathogenesis and pathophysiology of IMIDs has been documented by extensive preclinical and clinical investigations, and confirmed by the efficacy of anti-TNF biotechnological drugs, such as etanercept, infliximab and adalimumab, in the therapeutic management of these disorders. In this narrative review, we discuss the available data on the TNF-dependent pathogenesis of IMIDs and associations among the different disorders. Although much remains to be discovered about the pathogenesis and aetiology of IMIDs, their common inflammatory pathological features may explain why they can be successfully targeted by anti-TNF drugs. Among these, adalimumab, a fully human monoclonal antibody, has been approved for treatment of nine distinct IMID indications and it is likely to become a valuable therapeutic tool for this complex cluster of chronic inflammatory disorders.

anti-TNF agents as therapeutic choice in immune-mediated inflammatory diseases: focus on adalimumab.

The complex pathogenesis of immune-mediated inflammatory diseases (IMIDs) has been extensively investigated and dysregulation of cytokines, such as tumour necrosis factor (TNF) has been shown to play a dominant role in the pathogenesis of various IMIDs, such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. The subsequent development of biological agents capable of blocking TNF has led to important advances in the pharmacotherapy of such diseases and confirmed the concept of a common pathophysiology among IMIDs with TNF having a predominant role. Five TNF inhibitors have currently been approved for treatment of one or more IMIDs; these include infliximab, etanercept, adalimumab, golimumab and certolizumab pegol. Given the similarities in the pathogenic background of IMIDs, one could expect that anti-TNF agents be similarly effective and with comparable tolerability profiles; however, this may not be the case. Structural and pharmacological differences among the anti-TNF drugs are likely to result in differences in efficacy and tolerability among the agents in the different IMIDs, together with differences in potency, therapeutic dose ranges, dosing regimens, administration routes, and propensity for immunogenicity. Among the five TNF inhibitors approved for treatment of IMIDs, adalimumab has the widest range of indications. Data from controlled clinical trials of adalimumab, showing its excellent efficacy and tolerability in a wide range of indications, are supported by real-world long-term data from observational studies, which confirm the value of adalimumab as a suitable choice in the management of IMIDs.

Adalimumab in the treatment of immune-mediated diseases.

Tumour necrosis factor (TNF) plays an important role in the pathogenesis of immune-mediated inflammatory diseases (IMIDs). TNF inhibition results in down-regulation of abnormal and progressive inflammatory processes, resulting in rapid and sustained clinical remission, improved quality of life and prevention of target organ damage. Adalimumab is the first fully human monoclonal antibody directed against TNF. In this article, we review the role and cost effectiveness of adalimumab in the treatment of IMIDs in adults and children. The efficacy and tolerability of adalimumab has been demonstrated in patients with a wide range of inflammatory conditions, leading to regulatory approval in rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis, inflammatory bowel diseases (Crohn's disease, ulcerative colitis, paediatric Crohn's disease, and intestinal Behçet's disease), ankylosing spondylitis (AS), axial spondyloarthritis (SpA) and juvenile idiopathic arthritis. The major tolerability issues with adalimumab are class effects, such as injection site reactions and increased risk of infection and lymphoma. As with all anti-TNF agents, adalimumab is immunogenic, although less than infliximab, and some patients receiving long-term adalimumab will develop anti-drug antibodies, causing a loss of response. Comparisons of its clinical utility and cost effectiveness have shown it to be a valid treatment choice in a wide range of patients. Recent data from Italian economic studies show the cost effectiveness of adalimumab to be below the threshold value for health care interventions for most indications. In addition, analysis of indirect costs shows that adalimumab significantly reduces social costs associated with RA, PsA, AS, Crohn's disease and psoriasis. The fact that adalimumab has the widest range of approved indications, many often presenting together in the same patient due to the common pathogenesis, may further improve the utility of adalimumab. Current clinical evidence shows adalimumab to be a valuable resource in the management of IMIDs. Further research, designed to identify patients who may benefit most from this drug, will better highlight the role and cost-effectiveness of this versatile TNF inhibitor.

Classification and clinical assessment.

There are at least nine classification criteria for psoriatic arthritis (PsA) that have been proposed and used in clinical studies. With the exception of the ESSG and Bennett rules, all of the other criteria sets have a good performance in identifying PsA patients. As the CASPAR criteria are based on a robust study methodology, they are considered the current reference standard. However, if there seems to be no doubt that they are very good to classify PsA patients (very high specificity), they might be not sensitive enough to diagnose patients with unknown early PsA. The vast clinical heterogeneity of PsA makes its assessment very challenging. Peripheral joint involvement is measured by 78/76 joint counts, spine involvement by the instruments used for ankylosing spondylitis (AS), dactylitis by involved digit count or by the Leeds dactylitis index, enthesitis by the number of affected entheses (several indices available) and psoriasis by the Psoriasis Area and Severity Index (PASI). Peripheral joint damage can be assessed by a modified van der Heijde-Sharp scoring system and axial damage by the methods used for AS or by the Psoriatic Arthritis Spondylitis Radiology Index (PASRI). As in other arthritides, global evaluation of disease activity and severity by patient and physician and assessment of disability and quality of life are widely used. Finally, composite indices that capture several clinical manifestations of PsA have been proposed and a new instrument, the Psoriatic ARthritis Disease Activity Score (PASDAS), is currently being developed.

Cardiovascular involvement in psoriatic arthritis.

Psoriasis is a chronic, genetically determined and immunomediated inflammatory skin disease that affects 2-3% of the Caucasian population. A considerable proportion of these patients develop a form of inflammatory arthritis known as psoriatic arthritis (PsA), although the prevalence of this has not been well defined. Patients with PsA have a higher mortality rate than the general population and the risk of mortality is related to disease severity at the time of presentation. Endothelial dysfunction and early atherosclerosis have been found in patients with PsA without any cardiovascular disease (CVD) risk factors, and experts believe that CVD is one of the leading causes of death, as it is in patients with rheumatoid arthritis (RA). Various disease-related mechanisms may be involved in the development of premature vascular damage in both cases, including an increased synthesis of proinflammatory mediators (such as cytokines, chemokines and adhesion molecules), autoantibodies against endothelial cell components, perturbations in T-cell subsets, genetic polymorphisms, hyperhomocysteinemia, oxidative stress, abnormal vascular repair, and iatrogenic factors. In a recent study of 22 patients with PsA without any signs of CVD, we found that the plasma concentration of asymmetric dimethylarginine (ADMA) levels were significantly high and coronary flow reserve (CFR) was significantly reduced. Moreover, there was a significant correlation between CFR and plasma ADMA levels in the PsA group. The significant correlation between the reduced CRF and increased ADMA levels suggests that, like patients with early RA, PsA patients suffer from endothelial dysfunction and impaired coronary microcirculation. Active PsA is a risk factor for CVD, and so PsA patients should be screened for subclinical forms of the disease and its risk factors, and an early treatment approach should be adopted.

Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus.

An inception cohort of patients with systemic lupus erythematosus from 14 European centres was followed for up to 5 years in order to describe the current early disease course. At inclusion patients (n = 200, 89% female, mean age 35 years, 97% Caucasian, mean SLEDAI 12.2) fulfilled a mean of 6.5 ACR classification criteria. The most prevalent criteria were antinuclear Ab presence (97%) followed by anti-dsDNA Ab (74%), arthritis (69%), leukocytopenia (54%) and malar rash (53%), antiphospholipid Ab (48%) and anti-synovial membrane Ab (21.6%). Clinical signs of lupus nephritis (LN) were present in 39% with biopsy-confirmed LN seen in 25%. Frequent additional findings were hypocomplementaemia (54%), anti-SSA Ab (49%), alopecia (26%) and Raynaud's phenomenon (31%). There were few regional differences in disease presentation and management. One and 5-year survival rates were 99% and 97% respectively. During the mean follow-up of 4.1 years 25% entered a state of early disease quiescence by global physician assessment, but the overall risk of subsequent flare was 60%. Maximum SLEDAI scores decreased over time, but 45% of patients accrued damage (SDI >or=1) for which baseline presence of proteinuria and persistent disease activity were independent predictors. The results indicate minor differences in SLE presentation and treatment within various regions of Europe and a high diagnostic reliance on anti-dsDNA Ab. Despite early reductions in disease activity and improved mortality, the risk for disease flare and damage development is, however, still substantial, especially in patients not entering an early remission.

An Italian shared dermatological and rheumatological proposal for the use of biological agents in psoriatic disease.

BACKGROUND: As psoriatic disease (PD) is a condition characterized by the combination of inflammatory skin (psoriasis) and osteo-articular manifestations (psoriatic arthritis), its treatment should cover both its clinical components. OBJECTIVE: The objective of this study was to propose a flexible framework for the use of biological agents in PD. METHODS: The proposal was drawn up by a group of dermatologists and rheumatologist expert in PD and was based on existing evidence and personal opinion. RESULTS: The three TNF-alpha inhibitors (adalimumab, etanercept, infliximab) are effective in all of the psoriatic manifestations and should be used in the case of moderate/severe disease refractory to systemic treatment with non-biological drugs. We propose the following definitions of moderate/severe disease: PASI > 10 or BSA > 10 or DLQI > 10 for plaque-psoriasis; BSA > or = 10 or DLQI > or = 10 for the other psoriatic skin lesions; DLQI > or = 10 or meaningful values of the NAPSI or mNAPSI for psoriatic nail involvement; > or = 1 inflamed joint + patient global VAS(3)4 + physician's judgement or arthritic joint deformities or radiographic joint damage plus > or = 5 inflamed small joints or > or = 1 large joints for peripheral joint involvement; > or = 1 digit with dactylitis and > or = 1 enthesitic sites + patient global VAS(3)4 + physician's judgement for dactylitis and enthesitis. BASDAI > or = 4 + physician's judgement for spondylitis; recurrent flares or risk of developing irreversible damage for uveitis. Other assessment instruments can be used if the physician is more familiar with them and if they have been validated. CONCLUSION We provide a shared dermatological and rheumatological proposal for the use of biological agents in PD.

[Long-term survival of methotrexate in psoriatic arthritis]. / Sopravvivenza a lungo termine del trattamento con methotrexate nell'artrite psoriasica.

OBJECTIVE: The purpose of this study was to evaluate the long-term survival rate of Methotrexate (MTX) in the peripheral joint involvement of psoriatic arthritis (PsA) in a setting of everyday clinical practice. METHODS: This was an observational restrospective study performed using the data from a dermatological-rheumatological PsA clinic. All of the patients evaluated at this clinic from March 1997 to December 2007 who were started on MTX alone, had a three-year follow-up time or had discontinued the therapy were included into the survey. RESULTS: Of the 174 evaluable patients, 104 (59.8%) were still taking MTX after three years of treatment. The reasons of therapy discontinuation in the remaining 70 (40.2%) patients were: 34 (19.5%) lost-to-follow-up, 18 (10.3%) adverse events, 14 (8%) inefficacies, and 4 (2.3%) deaths (none related to the therapy). MTX was effective in controlling joint inflammation but not in preventing their deterioration. Overall, adverse events were recorded in 43 patients (36.4% of the 114 patients with a three-year follow-up). No serious side effect occurred in the study population. CONCLUSIONS: The results of this study showed that, in a setting of clinical pratice, MTX had a good three-year performance in patients with peripheral PsA. Almost 60% of them were still taking this drug at the end of the study period and the toxicity was more than acceptable. In our opinion, MTX might be considered the non-biological DMARD of choice for the treatment of this condition. However it should be used earlier and at higher doses.

The radiological assessment of axial involvement in psoriatic arthritis: a validation study of the BASRI total and the modified SASSS scoring methods.

OBJECTIVES: To assess the validity of the BASRI and m-SASSS scores for the radiological axial involvement in psoriatic arthritis (PsA). Secondary end-points were to report on clinical, functional and radiographic characteristics of axial involvement. METHODS: Inclusion criteria were satisfaction of the CASPAR criteria and the presence of clinical, functional and/or radiological axial involvement. Three observers scored the radiographs by BASRI and m-SASSS. The construct validity was assessed by examining the correlation of instruments with patient reported outcomes and anthropometric measures. The reliability and the feasibility of the scores were also considered. RESULTS: Seventy-seven patients were enrolled (58 M, 19 F, mean age 49.4 + or - 10.8 yrs, disease duration 13.9 + or - 7.9 yrs). Both instruments showed some modest but significant correlation with clinical measures. When compared, the BASRI showed a correlation with BASMI (rho=0.47, p<0.001), cervical rotation (rho=-0.49, p<0.001), tragus to wall (rho=0.34, p<0.01) and occiput to wall (rho=0.49, p<0.001), modified Schober test (rho=-0.24, p<0.05) and RLDQ (rho=-0.24, p<0.05). When compared, m-SASSS showed a correlation with BASMI (rho=0.39, p<0.001), cervical rotation (rho=-0.41, p<0.001), tragus to wall (rho=0.31, p<0.01) and occiput to wall (rho=0.42, p<0.001), modified Schober and Schober test (rho=-0.34, p<0.001; rho= -0.32, p<0.01), finger to floor (rho=0.37, p<0.01). No correlation was found with BASFI, BASDAI and HAQ. Test-retest showed a good reliability of the scores. Both were feasible but BASRI was the quickest. CONCLUSION: Our results showed that BASRI and m-SASSS were valid instruments for use in spondylitis associated with psoriatic arthritis. Longitudinal data is required to provide sensitivity to change of the two scores.

Pattern of use, economic burden and vial optimization of infliximab for rheumatoid arthritis in Italy.

OBJECTIVE: The aim of this study was to retrospectively examine the pattern of utilization in clinical practice and the costs of therapy of infliximab in the treatment of refractory rheumatoid arthritis (RA). METHODS: Ninety-five RA patients (22 newly treated and 73 maintenance patients) who received at least one infliximab infusion during a selected observation period of one year were studied. After induction phase, infliximab was given at initial dose of 3 mg/kg every 8 weeks. Based on clinical efficacy measured by Disease Activity Score 28 (DAS 28) index, dose adjustments were performed by increasing pro kg dose and/or reducing infusion interval. Overall one-year's treatment costs were also examined. RESULTS: Sixteen (17%) out of 95 patients discontinued treatment before the end of the study owing to lack of efficacy (15) or adverse events (1). Thirteen (59%) out of 22 newly treated patients experienced treatment escalation in the first year of therapy by increasing dose (13.6%), reducing interval (9%), or both (36.3%). The mean infliximab dose administered to all the patients was 3.57 mg/kg and the mean infusion interval was 50 days. Considering all expenditure items, the mean year treatment cost per patient was euro 8454,65. Infliximab vial optimization allows us to reduce this amount to euro 7505,85, with a significant saving of euro 948,80 per patient/year. CONCLUSIONS: In this observational study, adjustments in infliximab treatment in the first year of therapy were common. Despite dose escalation, the mean dosing schedule does not significantly differ from those recommended in the product label. The cost of treatment could be reduced by using infliximab vial optimization.

Efficacy and safety of anti-TNF agents in the Lombardy rheumatoid arthritis network (LORHEN).

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis and bone damages, which consist of joint destruction. Clinical trials have shown that anti-tumour necrosis factor (TNF) drugs are effective in patients with rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drugs (DMARDs). At about the same time as the European approval of the third anti-TNF agent for treating rheumatoid arthritis (RA) patients, the Italian Society of Rheumatology (Società Italiana di Reumatologia [SIR]) started a database for the registration and active follow-up of patients with RA treated with biological response modifiers. Since 1999, all patients with RA (ACR criteria) and treated with at least one dose of an anti-TNF agent at four Rheumatology Centres in Lombardy (northwest Italy) have been included in the Lombardy Rheumatology Network (LORHEN) registry in order to track the efficacy and safety of the three available TNF inhibitors during the first three years of treatment.

Current causes of death in systemic lupus erythematosus in Europe, 2000--2004: relation to disease activity and damage accrual.

Current therapeutic and diagnostic resources have turned systemic lupus erythematosus (SLE) into a chronic disease by reducing mortality rates. The exact contribution of disease activity and disease related damage to mortality is not well studied. The aim of this study was to describe the current causes of death (COD) in a multinational European cohort of patients with SLE in relation to quantified measures of disease activity and damage. Prospective five-year observational study of case fatalities in SLE patients at 12 European centres was performed. Demographics, disease manifestations, interventions and quantified disease activity (by ECLAM and SLEDAI) and damage (by SLICC-DI) at the time of death were related to the various COD. Ninety-one case fatalities (89% females) occurred after median disease duration of 10.2 years (range 0.2-40) corresponding to a annual case fatality of one for each of the participating cohorts. Cumulative mortality correlated linearly with disease duration with nearly 10% of fatalities occurring in the first year and 40% after more than 10 years of disease. Death occurred during SLE remission in one third of cases. In the remaining cases a mixture of disease activity (median ECLAM 5.5, median SLEDAI 15) and accrued damage (median SLICC-DI 5.0) with opposing relationships to disease duration contributed to death. Infections and cardiovascular events were the most frequent COD in both early and late fatalities with no gender differences for type of COD, disease activity, damage or comorbidity. In Europe, case fatalities have become uncommon events in dedicated SLE cohorts. The bimodal mortality curve has flattened out and deaths now occur evenly throughout the disease course with infectious and cardiovascular complications as the main direct COD in both early and late fatalities. Accrued damage supplants disease activity over time as the main SLE specific contributor to death over time.

Recommendations of the Italian Society for Rheumatology for the use of biologic (TNF-alpha blocking) agents in the treatment of psoriatic arthritis.

AIM: To propose recommendations for the use of biologic (TNF-alpha blocking) agents in the treatment of psoriatic arthritis (PsA). METHODS: We developed these recommendations by reviewing the evidence published in medical journals and in abstracts of the American College of Rheumatology (ACR) and of the European League against Rheumatism. A draft of the recommendations was circulated to a group of Italian Rheumatologists with a special interest in PsA and in therapy with biologic agents, and their suggestions were incorporated in the final version. RESULTS: A consensus was achieved regarding the initiation and the monitoring of anti-TNF-alpha agents in PsA. More specifically, we propose that anti-TNF-alphaagents be considered in active PsA resistant to non-steroidal anti-inflammatory drugs, to at least two local steroid injections and at least 2 conventional disease-modifying anti-rheumatic agents (in cases of oligo/monoarthritis and/or enthesitis), and to at least two conventional disease-modifying anti-rheumatic agents (in patients with peripheral joints synovitis). Disease activity monitoring should be based on a variety of outcome measures including the ACR response criteria modified for use in PsA, the Bath ankylosing spondylitis disease activity index (BASDAI), and the Maastricht ankylosing spondylitis enthesis score (MASES). A favorable Expert opinion, based on evaluation of clinical symptoms and signs, of laboratory investigations (particularly acute phase reactants), and of imaging studies (whenever appropriate) should also be obtained. CONCLUSION: These recommendations may be used for guidance in deciding which patients with PsA should receive biologic therapy. Regular updates of these recommendations will be implemented on the basis of the results of new clinical studies and of data from post-marketing surveillance.