Organ damage is a major determinant of work productivity impairment in Behçet's Syndrome: a post-hoc analysis of the BODI validation study.

OBJECTIVES: To evaluate the prevalence, magnitude, and potential determinants of work productivity impairment in patients with Behçet's Syndrome (BS), focusing on the role of irreversible organ damage. METHODS: A post-hoc analysis of the BS overall damage index (BODI) prospective validation study was performed. Demographics and clinical features were recorded in all patients. The Work Productivity and Activity Impairment: General Health (WPAI: GH) questionnaire was administered to assess the work limitation and the BODI to measure organ damage. The independent effect of BS features on WPAI: GH outcomes was evaluated by regression analysis. RESULTS: Out of 148 patients, 34.5% were unemployed, with age (OR 1.035) and BODI score (OR 1.313 for 1-unit increase) as the only factors significantly (p< 0.05) associated with the unemployment state. An overall work impairment was reported in about 64.2% of the employed patients. Indeed, 22.7% reported missing work h due to their health (absenteeism), with a mean time loss of 34.4%; whereas 60.2% declared a reduced performance at work because of their health (presenteeism), with a mean productivity impairment of 45.4%. Ocular damage was associated with absenteeism (ß 0.225); female sex (ß 0.260), physician global assessment of disease activity (ß 0.502) and an increased BODI score (ß 0.166 for 1-point increase) with presenteeism; fibromyalgia (ß 0.246), physician global assessment (ß 0.469), and musculoskeletal damage (ß 0.325) with overall work impairment. CONCLUSIONS: Disease activity and organ damage accrual remarkably affect work productivity in BS patients. Achieving remission and preventing damage accrual are crucial and complementary objectives.

Accrual of organ damage in Behçet's syndrome: trajectory, associated factors, and impact on patients' quality of life over a 2-year prospective follow-up study.

BACKGROUND: This study aimed to investigate the trajectory of damage accrual, associated factors, and impact on health-related quality of life (HR-QoL) in a multicenter cohort of patients with Behçet's syndrome (BS) over 2 years of follow-up. METHODS: Patients recruited in the BS Overall Damage Index (BODI) validation study were prospectively monitored for 2 years and assessed for damage accrual, defined as an increase ≥1 in the BODI score, and HR-QoL was evaluated by the SF-36 questionnaire. Logistic and multiple linear regression models were built to determine factors associated with damage accrual and impairment in the different SF-36 domains. RESULTS: During follow-up, 36 out of 189 (19.0%) patients had an increase ≥1 in the BODI score with a mean (SD) difference of 1.7 (0.8) (p <0.001). The incidence rate of damage accrual was stable over time, regardless of the disease duration. Out of 61 new BODI items, 25 (41.0%) were considered related to glucocorticoid (GC) use. In multivariate analysis, duration of GC therapy (OR per 1-year 1.15, 95% CI 1.07-1.23; p <0.001) and occurrence of ≥1 disease relapse (OR 3.15, 95% CI 1.09-9.12; p 0.038) were identified as predictors of damage accrual, whereas the use of immunosuppressants showed a protective effect (OR 0.20, 95% CI 0.08-0.54, p<0.001). Damage accrual was independently associated with the impairment of different physical domains and, to a greater extent, in emotional domains of the SF-36 questionnaire. Female sex, higher disease activity, and fibromyalgia were also significantly associated with impairment in HR-QoL. CONCLUSION: In BS, organ damage accrues over time, also in long-standing disease, resulting in an impairment of the perceived physical and mental health. Adequate immunosuppressive treatment, preventing disease flares and minimizing exposure to GCs have a crucial role in lowering the risk of damage accrual.

An Italian Multicenter Study on Anti-NXP2 Antibodies: Clinical and Serological Associations.

The identification of anti-NXP2 antibodies is considered a serological marker of dermatomyositis (DM), with calcinosis, severe myositis and, in some reports, with cancer. Historically, these associations with anti-NXP2 antibodies have been detected by immunoprecipitation (IP), but in the last few years commercial immunoblotting assays have been released. The aim of this collaborative project was to analyse the clinical features associated to anti-NXP2 antibodies, both with commercial line blot (LB) and IP. Myositis-specific and myositis-associated autoantibodies were detected in single centres by commercial line blot (LB); available sera were evaluated in a single centre by protein and RNA immunoprecipitation (IP), and IP-Western blot. Sixty patients anti-NXP2+ (NXP2+) positive by LB were compared with 211 patients anti-NXP2 negative with idiopathic inflammatory myositis (IIM). NXP2+ showed a younger age at IIM onset (p = 0.0014), more frequent diagnosis of dermatomyositis (p = 0.026) and inclusion-body myositis (p = 0.009), and lower rate of anti-synthetase syndrome (p < 0.0001). As for clinical features, NXP2+ more frequently develop specific skin manifestations and less frequently features related with overlap myositis and anti-synthetase syndrome. IP confirmed NXP2 positivity in 31 of 52 available sera (62%). Most clinical associations were confirmed comparing NXP2 LB+/IP+ versus NXP2-negative myositis, with the following exceptions: inclusion-body myositis diagnosis was not detected, whilst dysphagia and myositis were found more frequently in NXP2 LB+/IP+ patients. The 21 LB+ /IP-myositis patients did not show differences in clinical features when compared with the NXP2-myositis patients and more frequently displayed multiple positivity at LB. Risk of developing cancer-associated myositis was similar between NXP2-positive and NXP2-negative myositis patients, either when detected by LB or IP. Protein-IP confirmed NXP2 antibodies in nearly 60% of sera positive for the same specificity with commercial assay. Double-positive cases rarely occurred in myositis patients with a clinical diagnosis other than dermatomyositis. Patients only positive by LB (LB+/IP-) did not display clinical features typical of NXP2. NXP2 positivity by LB should be confirmed by other methods in order to correctly diagnose and characterize patients affected by idiopathic inflammatory myositis.

Current smoking predicts inadequate response to methotrexate monotherapy in rheumatoid arthritis patients naïve to DMARDs: Results from a retrospective cohort study.

ABSTRACT: Identifying predictors of inadequate response to methotrexate (MTX) in rheumatoid arthritis (RA) is key to move from a "trial and error" to a "personalized medicine" treatment approach where patients less likely to adequately respond to MTX monotherapy could start combination therapy at an earlier stage. This study aimed to identify potential predictors of inadequate response to MTX in RA patients naïve to disease modifying anti-rheumatic drugs.Data from a real-life cohort of newly diagnosed RA patients starting MTX (baseline, T0) as first-line therapy were analyzed. Outcomes, assessed after 6 months (T1), were defined as failure to achieve a disease activity score 28 (DAS28) low disease activity (LDA) or a good/moderate response to MTX, according to the European League Against Rheumatism (EULAR) response criteria. Logistic regression was used to assess the associations between baseline variables and the study outcomes.Overall, 294 patients (60.5% females, median age 54.5 years) with a median disease duration of 7.9 months were recruited. At T1, 47.3% of subjects failed to achieve LDA, and 29.3% did not have any EULAR-response. In multivariate analysis, significant associations were observed between no LDA and current smoking (adjusted odds ratio [adjOR] 1.79, P = .037), female gender (adjOR 1.68, P = .048), and higher DAS28 (adjOR 1.31, P = .013); and between no EULAR-response and current smoking (adjOR: 2.04, P = .019), age (adjOR: 0.72 per 10-years increases, P = .001), and higher erythrocyte sedimentation rate (adjOR: 0.49; P = .020). By contrast, there were no associations between past smoker status and study outcomes.In summary, in our real-life cohort of disease modifying anti-rheumatic drug naïve RA patients, current smoking habit independently predicts inadequate response to MTX. This, together with other independent predictors of response to treatment identified in our study, might assist with personalized monitoring in RA patients. Further studies are required to investigate whether smoking quitting strategies enhance the therapeutic response to MTX.

Biologics and Targeted Synthetic Drugs Can Induce Immune-Mediated Glomerular Disorders in Patients with Rheumatic Diseases: An Updated Systematic Literature Review.

OBJECTIVE: Our objective was to update the understanding of the development of paradoxical immune-mediated glomerular disorders (IGDs) in patients with rheumatic diseases treated with biologics and targeted synthetic drugs (ts-drugs). METHODS: A systematic literature review was performed by searching PubMed for articles published between 1 January 2014 and 1 January 2020 reporting on the development of IGD in adult patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or systemic lupus erythematosus (SLE) who were receiving biologics or ts-drugs. IGDs were classified on the basis of clinical, laboratory and histopathological data as (1) glomerulonephritis associated with systemic vasculitis (GNSV), (2) isolated autoimmune renal disorder (IARD) or (3) glomerulonephritis in SLE and in lupus-like syndrome (GNLS). The World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment was applied to evaluate the causal relationship between IGD and specific drugs. The classification was based on a six-category scale, where the "certain" and "probable" categories were deemed clinically relevant relationships. RESULTS: The literature search retrieved 875 articles. Of these, 16 articles reported IGD data, for a total of 25 cases. According to the WHO-UMC assessment, the strength of the causal relationship between IGDs and investigated drugs was higher for anti-tumor necrosis factor-α agents (a clinically relevant relationship was found in four of six cases), abatacept (one of two cases), tocilizumab (two cases), ustekinumab (one case) and tofacitinib (one case) than for rituximab (nine cases), belimumab (three cases) or secukinumab (one case), which showed a weak causal relationship with these paradoxical events. No cases associated with apremilast or baricitinib were found. The retrieved cases were classified as 11 GNLS, seven IARD and seven GNSV. CONCLUSIONS: Biologics and ts-drugs can cause IGDs. These events are rare, and the causative effect of a specific drug is hard to establish. When a patient is suspected of having an IGD, the drug should be discontinued, and treatment for the new-onset renal disorder should be promptly started.

Assessment Of Circulating Endothelial Cells And Their Progenitors As Potential Biomarkers Of Disease Activity And Damage Accrual In Behçet's Syndrome.

PURPOSE: To explore the potential role of circulating endothelial cells (CECs) and their progenitors (EPCs) as biomarkers of disease activity and damage accrual in patients with Behçet's syndrome (BS), by using a standardised and reliable flow cytometry protocol. PATIENTS AND METHODS: CECs and EPCs were assessed in 32 BS patients and 11 gender/age/smoking habits matched healthy controls (HC). They were identified by flow cytometry as alive/nucleated/CD45-negative/CD34-bright/CD146-positive and alive/nucleated/CD45-negative/CD34-bright/CD309-positive events, respectively. In BS patients, demographic and clinical features, including disease activity (assessed by Behçet's disease current disease activity form, BDCAF) and irreversible damage accrual (by the vasculitis damage index, VDI) were recorded. Uni- and multivariate analysis were performed to compare the CECs and EPCs concentrations in BS vs HC and to identify potential associations with demographic or clinical features. RESULTS: The CECs concentration was significantly higher in the BS patients than HCs [median (IQR) 15.0 (7.5-23.0) vs 6.0 (2.0-13.0) CECs/mL, p=0.024]. In BS patients, no significant associations were found between CECs and demographic features, present and past clinical manifestations, BDCAF score and ongoing treatment. A significant association was observed between CECs and organ damage, as assessed by the VDI (rho 0.356, p=0.045). Higher levels of CECs were especially associated with vascular damage [median (IQR) 23.0 (14.0-47.0) vs 13.0 (6.0-19.0) CECs/mL, p=0.011], including arterial aneurysm and stenosis, complicated venous thrombosis, cerebrovascular accident. The concentration of EPCs did not significantly differ between the BS and HC [median 26.5 (13.0-46.0) vs 19.0 (4.0-42.0) EPCs/mL, p=0.316] and no significant associations were observed between their levels and any clinical characteristic. CONCLUSION: Our study suggests that the CECs concentration is significantly higher in BS than healthy subjects, and it mainly correlates with vascular damage. A longitudinal extension of the present study on a wider cohort would be useful to validate the potential role of CECs as a marker or, hopefully, predictor of vascular damage in BS.

Unusual Placement of an EBV Epitope into the Groove of the Ankylosing Spondylitis-Associated HLA-B27 Allele Allows CD8+ T Cell Activation.

The human leukocyte antigen HLA-B27 is a strong risk factor for Ankylosing Spondylitis (AS), an immune-mediated disorder affecting axial skeleton and sacroiliac joints. Additionally, evidence exists sustaining a strong protective role for HLA-B27 in viral infections. These two aspects could stem from common molecular mechanisms. Recently, we have found that the HLA-B*2705 presents an EBV epitope (pEBNA3A-RPPIFIRRL), lacking the canonical B27 binding motif but known as immunodominant in the HLA-B7 context of presentation. Notably, 69% of B*2705 carriers, mostly patients with AS, possess B*2705-restricted, pEBNA3A-specific CD8+ T cells. Contrarily, the non-AS-associated B*2709 allele, distinguished from the B*2705 by the single His116Asp polymorphism, is unable to display this peptide and, accordingly, B*2709 healthy subjects do not unleash specific T cell responses. Herein, we investigated whether the reactivity towards pEBNA3A could be a side effect of the recognition of the natural longer peptide (pKEBNA3A) having the classical B27 consensus (KRPPIFIRRL). The stimulation of PBMC from B*2705 positive patients with AS in parallel with both pEBNA3A and pKEBNA3A did not allow to reach an unambiguous conclusion since the differences in the magnitude of the response measured as percentage of IFNγ-producing CD8+ T cells were not statistically significant. Interestingly, computational analysis suggested a structural shift of pEBNA3A as well as of pKEBNA3A into the B27 grooves, leaving the A pocket partially unfilled. To our knowledge this is the first report of a viral peptide: HLA-B27 complex recognized by TCRs in spite of a partially empty groove. This implies a rethinking of the actual B27 immunopeptidome crucial for viral immune-surveillance and autoimmunity.

Ankylosing Spondylitis: A Trade Off of HLA-B27, ERAP, and Pathogen Interconnections? Focus on Sardinia.

The frequency of HLA-B27 in patients with Ankylosing Spondylitis (AS) is over 85%. There are more than 170 recognized HLA-B27 alleles but the majority of them is not sufficiently represented for genetic association studies. So far only two alleles, the HLA-B*2706 in Asia and the HLA-B*2709 in Sardinia, have not been found to be associated with AS. The highly homogenous genetic structure of the Sardinian population has favored the search of relevant variants for disease-association studies. Moreover, malaria, once endemic in the island, has been shown to have contributed to shape the native population genome affecting the relative allele frequency of relevant genes. In Sardinia, the prevalence of HLA-B*2709, which differs from the strongly AS-associated B*2705 prototype for one amino acid (His/Asp116) in the F pocket of the peptide binding groove, is around 20% of all HLA-B27 alleles. We have previously hypothesized that malaria could have contributed to the establishment of this allele in Sardinia. Based on our recent findings, in this perspective article we speculate that the Endoplasmic Reticulum Amino Peptidases, ERAP1 and 2, associated with AS and involved in antigen presentation, underwent co-selection by malaria. These genes, besides shaping the immunopeptidome of HLA-class I molecules, have other biological functions that could also be involved in the immunosurveillance against malaria.

Switch or swap strategy in rheumatoid arthritis patients failing TNF inhibitors? Results of a modified Italian Expert Consensus.

Objective: To establish evidence-based and experts' opinion filtered statements on the optimal treatment choice between cycling (switch) and changing mode of action strategies (swap) in RA patients failing TNF inhibitors (TNFis). Methods: The relevant question (switch vs swap) was rephrased into a research question according to the population, intervention, comparison and outcome (PICO) strategy, considering all the available scientific evidence published from the 2013 EULAR set of recommendations up to mid-January 2016. Final statements derived from the retrieved scientific evidence and experts' consensus, with eventual rephrasing through a Delphi method during a national consensus of Italian rheumatologists. Results: From a total of 365 records, 12 studies were finally included. The final statements argued that, until head-to-head comparison data are available, switch and swap can be still considered suitable strategies in RA patients failing first TNFi, even though some data seem to lend more support to a different mode of action-targeted strategy. Conclusion: After failure of first TNFi course, switch and swap can be currently considered as alternative suitable approaches in RA patients.

Physician's Global Assessment in Psoriatic Arthritis: A Multicenter GRAPPA Study.

OBJECTIVE: Physician's global assessment (PGA) of disease activity is a major determinant of therapeutic decision making. This study assesses the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional use of separate VAS scales for musculoskeletal (PhysMSK) and dermatologic (PhysSk) manifestations in patients with psoriatic arthritis (PsA). METHODS: Sixteen centers from 8 countries enrolled 319 consecutive patients with PsA. PGA, PhysMSK, and PhysSk evaluation forms were administered at enrollment (W0) and after 1 week (W1). Detailed clinical data regarding musculoskeletal (MSK) manifestations, as well as dermatological assessment, were recorded. RESULTS: Comparison of W0 and W1 scores showed no significant variation (intraclass correlation coefficients were PGA 0.87, PhysMSK 0.86, PhysSk 0.78), demonstrating the reliability of the instrument. PGA scores were dependent on PhysMSK and PhysSk (p < 0.0001) with a major effect of the MSK component (B = 0.69) compared to skin (B = 0.32). PhysMSK was correlated with the number of swollen joints, tender joints, and presence of dactylitis (p < 0.0001). PhysSk scores were correlated with the extent of skin psoriasis and by face, buttocks or intergluteal, and feet involvement (p < 0.0001). Finally, physician and patient assessments were compared showing frequent mismatch and a scattered dot plot: PGA versus patient's global assessment (r = 0.36), PhysMSK versus patient MSK (r = 0.39), and PhysSk versus patient skin (r = 0.49). CONCLUSION: PGA assessed by means of VAS is a reliable tool to assess MSK and dermatological disease activity. PGA may diverge from patient self-evaluation. Because MSK and skin/nail disease activity may diverge, it is suggested that both PhysMSK and PhysSk are assessed.

Prevalence and Determinants of Peripheral Microvascular Endothelial Dysfunction in Rheumatoid Arthritis Patients: A Multicenter Cross-Sectional Study.

OBJECTIVES: To define the prevalence and determinants of peripheral microvascular endothelial dysfunction (ED) in a large series of rheumatoid arthritis (RA) patients free of previous cardiovascular events. MATERIALS AND METHODS: Data from 874 RA patients enrolled in the EDRA study (Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis-ClinicalTrials.gov: NCT02341066) were analyzed. Log-transformed reactive hyperemia index (Ln-RHI) was evaluated by peripheral arterial tonometry (PAT) using the EndoPAT2000 device: values of Ln-RHI < 0.51 were considered indicative of peripheral ED. RESULTS: Peripheral microvascular ED was documented in one-third of RA patients (33.5%); in multiple logistic regression analysis, ACPA negativity and higher triglycerides concentrations were independently associated with the presence of peripheral ED [OR (95% CI) = 1.708 (1.218-2.396), p < 0.01 and OR (95% CI) = 1.005 (1.002-1.009), p < 0.01, respectively]. Multiple regression analysis showed a positive correlation between Ln-RHI values and systolic blood pressure and HDL cholesterol levels; furthermore, higher values of Ln-RHI were associated with ACPA positivity, while smoking habit was associated with lower Ln-RHI values. CONCLUSIONS: This study demonstrates for the first time a high prevalence of peripheral microvascular ED in patients with RA free of previous cardiovascular events that appear to be only partially driven by traditional cardiovascular risk factors. The association between ACPA negativity and ED warrants further exploration.

Recommendations for the use of biologics and other novel drugs in the treatment of psoriatic arthritis: 2017 update from the Italian Society of Rheumatology.

OBJECTIVES: To update the 2011 Italian Society of Rheumatology (SIR) recommendations for the use of biologics and other novel agents in the treatment of psoriatic arthritis (PsA). METHODS: To create this new set of recommendations, the SIR "Spondyloartritis and Psoriatic Arthritis study group - A. Spadaro" went through the following steps: literature search, identification of the items of interests for each of the four previously identified clinical domains of PsA and the different treatment phases, achievement of the consensus on all topics, and generation of the recommendations. RESULTS: An update on the available evidence on all of the biologics and new small molecules tested in PsA is reported, comprising the data for each of the individual articular manifestation. Indications for therapy inclusion criteria, choice of the drug, disease assessment, response definition, therapy failure management, and disease remission management for PsA peripheral joint arthritis, enthesitis, dactylitis, and spondylitis are provided. Suggestions for the treatment of patients with PsA and concomitant extra-articular manifestations are also given. CONCLUSIONS: These evidence-based recommendations may be used for guidance in the complex and fast-evolving field of the treatment of PsA.

Telemedicine for patients with rheumatic diseases: Systematic review and proposal for research agenda.

OBJECTIVE: To systematically review the scientific literature regarding tele-rheumatology and draw conclusions about feasibility, effectiveness, and patient satisfaction. METHODS: PubMed, Scopus, and Cochrane database searches were performed (April 2016) using relevant MeSH and keyword terms for telemedicine and rheumatic diseases. Articles were selected if reporting outcomes for feasibility, effectiveness, and patient satisfaction and methodologically appraised using the Cochrane Collaboration's tool for assessing risk of bias and a modified version of CONSORT 2010 Statement. RESULTS: A total of 177 articles were screened, 23 were selected for the present review but only 9 were RCTs. Five studies reported on feasibility, 14 effectiveness, and 9 satisfaction rates for different tele-rheumatology interventions grouped in synchronous (remotely delivered consultation) and asynchronous (remote disease activity assessment; tele-monitoring of treatment strategies or rehabilitation; and remotely delivered self-management programs). Seven studies (30.4%) were on rheumatoid arthritis, 2 (8.7%) were on systemic sclerosis (1 including also rheumatoid arthritis patients), 5 (21.7%) on fibromyalgia, 2 (8.7%) on osteoarthritis, 3 (13.0%) on juvenile idiopathic arthritis and 4 (17.4%) on mixed disease cohorts. Interventions and outcomes heterogeneity prevented meta-analysis of results. Overall, feasibility and patient satisfaction rates were high or very high across intervention types. Effectiveness was equal or higher than standard face-to-face approach in controlled trials which, however, were affected by small sample size and lack of blinding participants according to appraisal tools. CONCLUSION: Telemedicine may provide a well-accepted way to remotely deliver consultation, treatment and monitoring disease activity in rheumatology. Higher quality RCTs demonstrating effectiveness of different tele-rheumatology interventions are needed.

Demyelinating syndrome in SLE encompasses different subtypes: Do we need new classification criteria? Pooled results from systematic literature review and monocentric cohort analysis.

OBJECTIVE: To describe features of demyelinating syndrome (DS) in systemic lupus erythematosus (SLE). METHODS: A systematic review using a combination of Mesh terms in PubMed and a retrospective analysis of 343 adult patients with SLE were carried out to identify patients with DS. Retrieved cases were classified as affected with DS according to 1999 ACR nomenclature and attributed to SLE by applying the 2015 algorithm. DS defined according to the clinical but not temporal 1999 ACR criteria was classified as clinically isolated syndrome (CIS). RESULTS: Estimated prevalence of DS (including CIS) in the SLE cohort was 1.3% and incidence rate was 1.5 cases per 1000 patient-years. Overall, 100 cases from literature review and 4 from SLE cohort were identified and are presented as a whole: 49 (47.1%) were classified as neuromyelitis optica spectrum disorders (NMOSD), 29 (27.9%) as CIS, 14 (13.5%) as NMO, 7 (6.7%) as DS prominently involving the brainstem and 5 (4.8%) as DS prominently involving the brain. DS was the SLE onset manifestation in 41 (39.4%) patients. Longitudinally extensive transverse myelitis was the most frequent manifestations being present in 73 (70.2%) patients (37 NMOSD, 21 CIS, 14 NMO, 1 DSB). Methylprednisolone (79.8%) and cyclophosphamide (55.8%) pulses, but also plasma-exchange (16.3%) and rituximab (7.6%) in relapsing-refractory cases, were mostly prescribed. Complete recovery rate ranged between 62% in CIS to 7% in NMO. CONCLUSION: DS in SLE is rare (1%) and encompasses different subtypes including CIS. Timely diagnosis and early treatment are recommended to minimize complications.

A national survey on the management of psoriatic arthritis using the Delphi method.

OBJECTIVES: Accurate diagnosis and appropriate management of psoriatic arthritis (PsA) is essential to avoid unnecessary morbidity. Our aim in this study was to evaluate the current approach to the management of PsA among rheumatologists. METHODS: A 16-item online questionnaire, produced using the Delphi method, was submitted to a panel of rheumatologists who anonymously expressed their opinions on a scale from 1 (maximum disagreement) to 5 (maximum agreement). Positive consensus was defined by ≥66% of the respondents scoring an item 3, 4 or 5. Negative consensus was defined by ≥66% of the respondents scoring an item 1 or 2. RESULTS: The surveyed rheumatologists agreed that in its early stage, PsA is characterised by the involvement of few joints and/or entheses and that psoriasis, although possibly absent, will be present in a patient's past personal or family history. There was no consensus among the rheumatologists regarding normalisation of C-reactive protein levels and erythrocyte sedimentation rates defining remission. The specialists believed that clinical remission was achieved more frequently and for longer among patients with PsA than rheumatoid arthritis. The participants believed that neutralising antibodies altered the efficacy of anti-tumour necrosis factor agents and that monoclonal antibodies induced greater production of neutralising antibodies than receptor proteins. However, knowledge was somewhat lacking in relation to the prophylaxis of latent tuberculosis. CONCLUSIONS: The data collected showed that the surveyed rheumatologists had a good knowledge of the diagnosis of early-stage PsA and a good understanding of its management in relation to its clinical phenotype, with the exception of the form having predominantly axial involvement.

Long-term costs and outcomes in psoriatic arthritis patients not responding to conventional therapy treated with tumour necrosis factor inhibitors: the extension of the Psoriatic Arthritis Cost Evaluation (PACE) study.

OBJECTIVES: Poor information on long-term outcomes and costs on tumour necrosis factor (TNF) inhibitors in psoriatic arthritis (PsA) are available. Our aim was to evaluate long-term costs and benefits of TNF- inhibitors in PsA patients with inadequate response to conventional treatment with traditional disease-modifying anti-rheumatic drugs (tDMARDs). METHODS: Fifty-five out of 107 enrolled patients included in the study at one year, completed the 5-year follow-up period. These patients were enrolled in 8 of 9 centres included in the study at one year. Patients aged older than 18 years, with different forms of PsA and failure or intolerance to tDMARDs therapy were treated with anti-TNF agents. Information on resource use, health-related quality of life (HRQoL), disease activity, function and laboratory values were collected at baseline and through the 5 years of therapy. Costs (expressed in Euro 2011) and utility (measured by EQ-5D instrument) before TNF inhibitor therapy and after 1 and 5 years were compared. RESULTS: The majority of patients (46 out of 55; 83.6%) had a predominant or exclusive peripheral arthritis and 16.4% had predominant or exclusive axial involvement. There was a statistically significant improvement of the most important clinical variables after 1 year of follow-up. These improvements were maintained also after 5 years. The direct costs increased by approximately €800 per patient-month after 1 year, the indirect costs decreased by €100 and the overall costs increased by more than €700 per patient-month due to the cost of TNF inhibitor therapy. Costs at 5 year were similar to the costs at 1 year. The HRQoL parameters showed the same trends of the clinical variables. EQ-5D VAS, EQ-5D utility and SF-36 PCS score showed a significant improvement after 1 year, maintained at 5 years. SF-36 MCS showed an improvement only at 5 years. CONCLUSIONS: The results of our study suggest that TNF blockers have long-term efficacy. The higher cost of TNF inhibitor therapy was balanced by a significant improvement of HRQoL, stable at 5 years of follow-up. Our results need to be confirmed in larger samples of patients.

Latent tuberculosis infection detection and active tuberculosis prevention in patients receiving anti-TNF therapy: an Italian nationwide survey.

AIMS: Primary: to investigate Italian rheumatology practice regarding latent tubercular infection (LTBI) detection and tuberculosis (TB) prevention in patients requiring anti-tumor necrosis factor (anti-TNF) therapy. Secondary: to assess the overall number of TB cases over 10 years and their distribution by drug. METHODS: An anonymous, 24 multiple-response questionnaire was completed by 393/449 (87.5%) rheumatologists prescribing anti-TNF therapy. Six questions provided setting information, and 18 the compliance with recommendations and the recorded TB cases. RESULTS: The Italian recommendations were used by 323 (82%) and other sets by 60 (15%). TB specialists were always consulted by 81 (21%) and occasionally by 73 (19%). LTBI screening was made using chest radiograph (CR) by 5%, tuburculin skin test (TST) by 5.3%, CR + TST by 35.6%, interferon-gamma release assay (IGRA) by 7.4%, CR + IGRAs by 26% and CR + TST + IGRA by 20.6%. Isoniazid was initiated in the presence of positivity of TST by 97 (24.7%), TST + IGRA by 101 (25.7%) and IGRA by 195 (49.6%). Anti-TNF starting delay was 1 month in 63.1% of the cases, 3 months in 27.7%, concomitantly in 5.6%. Overall, 317 TB reactivation cases occurred in 39 353 patients, with an incidence rate of 80.5 cases/100 000/year (10 times higher than in the Italian general population). TB occurred during TB prophylaxis in 192 (60.6%). TB cases incidence rate divided by drug was: etanercept (ETN) 51 (16%), 28/100 000/year, adalimumab (ADA) 98 (31%), 89/100 000/year, infliximab (IFX) 137 (43.2%), 211/100 000/year, with a significantly lower frequency in the ETN group compared to ADA and IFX groups (χ(2)  = P < 0.001). CONCLUSION: Italian rheumatologists are highly aware of anti-TNF-related TB risk with variable LTBI screening and TB prevention strategies. TB outcome was significantly lower in the ETN group.

New Approaches in Tumor Necrosis Factor Antagonism for the Treatment of Psoriatic Arthritis: Certolizumab Pegol.

The pathogenesis of psoriatic arthritis (PsA) is still under discussion but great advances have been made in the last 2 decades that confirm the central role of tumor necrosis factor-α (TNF-α) in its inflammatory milieu. New therapeutic approaches have been proposed, and new molecules with anti-TNF-α activity have been chemically altered to improve their pharmacological properties. Certolizumab pegol (CZP) is a PEGylated Fc-free anti-TNF that has been shown clinically to be effective in the treatment of rheumatoid arthritis (RA), skin psoriasis, and PsA. This article summarizes available data on its clinical efficacy and safety profile in the treatment of patients with PsA.

The adherence to ASAS classification criteria and to ASAS recommendations for the use of anti-TNH-alpha agents in axial spondyloarthritis.

OBJECTIVES: To determine the adherence of practicing rheumatologists, before and after an educational project, to Assessment of SpondyloArthritis international Society (ASAS) classification criteria and to ASAS recommendations for the use of anti-tumor necrosis factor (TNF)-alpha agents in patients with axial spondyloarthritis (SpA). METHODS: The project involved 53 rheumatologists attending 2 educational meetings on an update of SpA. Each meeting included interactive sessions on 1) clinical cases, 2) clinimetric evaluation, including ASAS core set for daily practice and 3) imaging. Diagnostic and therapeutic approach of each participant was tested using short clinical cases, obtained from real-life rheumatology settings, at the beginning and at the end of this educational project. Each case for diagnostic (n=10) or therapeutic purpose (n=10) had 10 possible choices. Each participant gave a score from 0 (total disagreement) to 10 (total agreement) for each choice. RESULTS: At baseline, the rheumatologists had an excellent agreement with ASAS classification criteria for axial SpA and anti-TNF-alpha treatment according to ASAS recommendations with a further significant improvement after the educational programme. In axial SpA cases with acute anterior uveitis (AU) or Crohn's disease, anti-TNF-alpha treatment was indicated mainly as monoclonal anti-TNF antibody. In presence of elevated levels of CRP, anti-TNF option has been considered useful. CONCLUSIONS: Practicing rheumatologists had a satisfying adherence to ASAS classification criteria and to ASAS recommendations for the use of anti-TNF-alpha agents for patients with axial SpA. Extra-articular manifestations and other variables might play a role in the decision-process of the management of axial SpA.

Biologics-induced autoimmune renal disorders in chronic inflammatory rheumatic diseases: systematic literature review and analysis of a monocentric cohort.

The use of biologic drugs has been linked with the paradoxical development of systemic and organ specific autoimmune processes. The aim of this study was to describe the features of biologics-induced autoimmune renal disorders (AIRD) through a systematic review and a cohort study of 707 adult patients affected with Rheumatoid Arthritis (RA), Ankylosing Spondylitis (SA) and Psoriatic Arthritis (PsA). The literature search identified 2687 articles of which 21 were considered relevant for the present study, accounting for 26 case reports. The cohort analysis retrieved 3 cases. According to clinical manifestations and kidney histology the identified AIRD cases were classified as: a) glomerulonephritis associated with systemic vasculitis (GNSV), b) glomerulonephritis in lupus-like syndrome (GNLS), c) isolated autoimmune renal disorders (IARD). Twenty-two out of 29 cases with AIRD were reported in patients affected by RA, 5 in AS and 2 in PsA. The biologic drug most frequently associated with development of AIRD was Etanercept (15 cases, 51.7%), followed by Adalimumab (9 cases, 31.0%) and Infliximab (3 cases, 10.3%) while Tocilizumab and Abatacept were reported in 1 case (3.4%) for each. Thirteen out of 29 (44.8%) cases were classified as affected by IARD, 12 (41.3%) as GNSV and 4 (13.9%) as GNLS. Worse prognosis was associated with GNSV and lack of biologic withdrawal. Although rare, AIRD may be life-threatening and may lead to renal failure and death. If AIRD occurs, biologic drugs must be stopped and patient should be treated according to clinical manifestations and kidney biopsy findings.