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Background/aim: to evaluate treatment adherence and predictors of drug discontinuation among patients with inflammatory arthritis receiving bDMARDs within the first 100 days after the announcement of the COVID-19 pandemic. Materials and methods: a total of 1871 patients recorded in TReasure registry for whom advanced therapy was prescribed for rheumatoid arthritis (RA) or spondyloarthritis (SpA) within the 3 months (6-9 months for rituximab) before the declaration of COVID-19 pandemic were evaluated, and 1394 (74.5%) responded to the phone survey. Patients' data regarding demographic, clinical characteristics and disease activity before the pandemic were recorded. The patients were inquired about the diagnosis of COVID-19, the rate of continuation on bDMARDs, the reasons for treatment discontinuation, if any, and the current general disease activity (visual analog scale, [VAS]). Results: a total of 1394 patients (493 RA [47.3% on anti-TNF] patients and 901 SpA [90.0% on anti-TNF] patients) were included in the study. Overall, 2.8% of the patients had symptoms suggesting COVID-19, and 2 (0.15%) patients had PCR-confirmed COVID-19. Overall, 18.1% of all patients (13.8% of the RA and 20.5% of the SpA; p = 0.003) discontinued their bDMARDs. In the SpA group, the patients who discontinued bDMARDs were younger (40 [21-73] vs. 44 years [20-79]; p = 0.005) and had higher general disease activity; however, no difference was relevant for RA patients. Conclusion: although the COVID-19 was quite uncommon in the first 100 days of the pandemic, nearly one-fifth of the patients discontinued bDMARDs within this period. The long-term effects of the pandemic should be monitored., Hacettepe Rheumatology Society

Objective: Currently, concerning the evaluation of psoriatic arthritis (PsA), there is no agreement on a standardized composite index for disease activity that includes all relevant domains. The present study sought to assess the rates of remission (REM)/low disease activity (LDA) and disease states [minimal disease activity (MDA), very low disease activity (VLDA)] as defined by diverse activity scales (DAPSA, DAS28-ESR) in an attempt to display discrepancies across these assessment tools for peripheral PsA. Methods: The study involved 758 patients (496 females, 262 males; mean age 47,1 years) with peripheral PsA who were registered to the Turkish League Against Rheumatism (TLAR) Network. The patients were assessed using the DAS28-ESR, DAPSA, MDA, and VLDA. The overall yield of each scale was assessed in identifying REM and LDA. The presence or absence of swollen joints was separately analysed. Results: The median disease duration was 4 years (range 0-44 years). According to DAPSA and DAS28-ESR, REM was achieved in 6.9% and 19.5% of the patients, respectively. The rates of MDA and VLDA were 16% and 2.9%, respectively. Despite the absence of swollen joints, a significant portion of patients were not considered to be in REM (296 (39.1%) patients with DAS28-ESR, 364 (48%) with DAPSA, and 394 (52%) with VLDA). Conclusion: Patients with peripheral PsA may be assigned to diverse disease activity levels when assessed with the DAS28-ESR, DAPSA, MDA and VLDA, which would inevitably have clinical implications. In patients with PsA a holistic approach seems to be necessary which includes other domains apart from joint involvement, such as skin involvement, enthesitis, spinal involvement, and patient-reported outcomes. © 2021 Société française de rhumatologie

ObjectivesTo develop predictive criteria for COVID-19-associated cytokine storm (CS), a severe hyperimmune response that results in organ damage in some patients infected with COVID-19. We hypothesised that criteria for inflammation and cell death would predict this type of CS.MethodsWe analysed 513 hospitalised patients who were positive for COVID-19 reverse transcriptase PCR and for ground-glass opacity by chest high-resolution CT. To achieve an early diagnosis, we analysed the laboratory results of the first 7 days of hospitalisation. We implemented logistic regression and principal component analysis to determine the predictive criteria. We used a ‘genetic algorithm’ to derive the cut-offs for each laboratory result. We validated the criteria with a second cohort of 258 patients.ResultsWe found that the criteria for macrophage activation syndrome, haemophagocytic lymphohistiocytosis and the HScore did not identify the COVID-19 cytokine storm (COVID-CS). We developed new predictive criteria, with sensitivity and specificity of 0.85 and 0.80, respectively, comprising three clusters of laboratory results that involve (1) inflammation, (2) cell death and tissue damage, and (3) prerenal electrolyte imbalance. The criteria identified patients with longer hospitalisation and increased mortality. These results highlight the relevance of hyperinflammation and tissue damage in the COVID-CS.ConclusionsWe propose new early predictive criteria to identify the CS occurring in patients with COVID-19. The criteria can be readily used in clinical practice to determine the need for an early therapeutic regimen, block the hyperimmune response and possibly decrease mortality.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder that primarily affects the joints. One hypothesis for the pathogenesis of RA is that disease begins at mucosal sites as a consequence of interactions between the mucosal immune system and an aberrant local microbiota, and then transitions to involve the synovial joints. Alterations in the composition of the microbial flora in the lungs, mouth and gut in individuals with preclinical and established RA suggest a role for mucosal dysbiosis in the development and perpetuation of RA, although establishing whether these alterations are the specific consequence of intestinal involvement in the setting of a systemic inflammatory process, or whether they represent a specific localization of disease, is an ongoing challenge. Data from mouse models of RA and investigations into the preclinical stages of disease also support the hypothesis that these alterations to the microbiota predate the onset of disease. In addition, several therapeutic options widely used for the treatment of RA are associated with alterations in intestinal microbiota, suggesting that modulation of intestinal microbiota and/or intestinal barrier function might be useful in preventing or treating RA.

Background There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group – KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients’ outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p Conclusion Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

Up to 40% of patients treated with tumor necrosis factor alpha inhibitors (TNFi) do not respond to therapy. Testing drug bioavailability and/or anti-drug antibody (ADAb) levels may justify dosage adjustment or switch to different drugs, enabling a personalized medicine approach. We report a multicenter cross-sectional study on different methods [ELISA and a cell based functional assay (reporter gene assay – RGA)] for drug/ADAb detection, and on the relationship between drug bioavailability and ADAb. 163 patients with rheumatoid arthritis (RA) treated with infliximab (IFX; n = 67), adalimumab (ADL; n = 49) or etanercept (ETA; n = 47) were tested for drug and ADAb levels. Furthermore, we report prospective data from additional 70 patients (59 RA and 11 juvenile idiopathic arthritis - JIA) tested for drug and ADAb levels at baseline (T0) and after 3 (T3) and 6 months (T6) of treatment with ADL or ETA only. IFX-treated patients were not included because of the increasing use of IFX biosimilars. Stringent inclusion criteria were used in order to avoid unwanted variables in both studies; none of the patients used TNFi before the study, and TNFi was used only in combination with methotrexate. Clinical response was defined according to EULAR response criteria. The two assays performed comparably in the comparison study. Accordingly, ELISA was selected for the prospective study because of its feasibility in the clinical setting. The cross-sectional study found ADAb in IFX and ADL treated groups only, that were associated with a decrease in pharmacological drug availability in the blood. Comparable results were found for the ADL-treated group in the prospective study which also showed a relationship between drug/ADAb levels and the loss of clinical response. Altogether our findings support drug and anti-drug Ab monitoring in the real-world clinical setting thus enabling individualized treatment and reducing disability in chronic inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is very complex and heterogeneous. If not adequately treated, RA patients are likely to manifest excess of morbidity and disability with an important impact on the quality of life. Pharmacological treatment is based on the administration of the disease-modifying antirheumatic drugs (DMARDs), subdivided into conventional synthetic (csDMARDs), targeted synthetic (tsDMARDs), and biological (bDMARDs). bDMARDs are now frequently administered in patients, both as alternative treatment and together with csDMARDs. Unfortunately, there is a therapeutic response variability both to old and new drugs. Therefore, to identify pre-therapeutic and on-treatment predictors of response is a priority. This review aims to summarize recent advances in understanding the causes of the variability in treatment response in RA, with particular attention to predictive potential of autoantibodies and DMARD pharmacogenetics. In recent years, several biomarkers have been proposed to personalize the therapy. Unfortunately, a magic bullet does not exist, as many factors concur to disease susceptibility and treatment outcomes, acting around the patient’s congenital background. Models integrating demographic, clinical, biochemical, and genetic data are needed to enhance the predictive capacity of specific factors singularly considered to optimize RA treatment in light of multidisciplinary patient management.

Introduction: In recent years, different studies regarding psoriatic arthritis (PsA) have shown the pathogenetic role of dysfunction of signaling pathways involving the phosphodiesterase-4 enzyme and transcription factors or enzymes belonging to the kinase (JAK)–signal family pathway. These also represent the target of several drugs known as targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs). Areas covered: The authors performed a systematic literature search using the PubMed database, as well as through retrieving data from randomized controlled trials, their post-hoc analysis, and pooled data analysis on the efficacy and safety profile of the PDE4 inhibitor (PDE4i), apremilast, and the inhibitors of JAK (JAKis), tofacitinib, filgotinib, baricitinib, and upadacitinib, in PsA. Expert opinion: In PsA, the PDE4i, apremilast, and the JAKi, tofacitinib, are effective across multiple clinical domains and have an acceptable tolerability profile, thus expanding the treatment options available for PsA patients. Apremilast and tofacitinib show several advantages mainly represented by their oral administration, a fast onset of action, and a short half-life. Data on tsDMARDs in PsA are still limited, and randomized trials and real-life studies are advocated.

IntroductionCovid-19 infection poses a serious challenge for immune-compromised patients with inflammatory autoimmune systemic diseases. We investigated the clinical-epidemiological findings of 1641 autoimmune systemic disease Italian patients during the Covid-19 pandemic.MethodThis observational multicenter study included 1641 unselected patients with autoimmune systemic diseases from three Italian geographical areas with different prevalence of Covid-19 [high in north (Emilia Romagna), medium in central (Tuscany), and low in south (Calabria)] by means of telephone 6-week survey. Covid-19 was classified as (1)definitediagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, confirmed by positive oral/nasopharyngeal swabs; (2)highly suspectedCovid-19 disease: presence of highly suggestive symptoms, in absence of a swab test.ResultsA significantly higher prevalence of patients withdefinitediagnosis of Covid-19 disease,or withhighly suspectedCovid-19 disease, or both the conditions together, was observed in the whole autoimmune systemic disease series, compared to “Italian general population” (p = .030,p = .001,p = .000, respectively); and fordefinite + highly suspecteddiagnosis of Covid-19 disease, in patients with autoimmune systemic diseases of the three regions (p = .000, for all comparisons with the respective regional general population).Moreover, significantly higher prevalence ofdefinite + highly suspecteddiagnosis of Covid-19 disease was found either in patients with various “connective tissue diseases” compared to “inflammatory arthritis group” (p p = .011).ConclusionsThe finding of a higher prevalence of Covid-19 in patients with autoimmune systemic diseases is particularly important, suggesting the need to develop valuable prevention/management strategies, and stimulates in-depth investigations to verify the possible interactions between Covid-19 infection and impaired immune-system of autoimmune systemic diseases.Key Points• Significantly higher prevalence of Covid-19 is observed in a large series of patients with autoimmune systemic diseases compared to the Italian general population, mainly due to patients’ increased susceptibility to infections and favored by the high exposure to the virus at medical facilities before the restriction measures on individual movement.• The actual prevalence of Covid-19 in autoimmune systemic diseases may be underestimated, possibly due to the wide clinical overlapping between the two conditions, the generally mild Covid-19 disease manifestations, and the limited availability of virological testing.• Patients with “connective tissue diseases” show a significantly higher prevalence of Covid-19, possibly due to deeper immune-system impairment, with respect to “inflammatory arthritis group”.• Covid-19 is more frequent in the subgroup of autoimmune systemic diseases patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs, mainly hydroxyl-chloroquine and methotrexate, which might play some protective role against the most harmful manifestations of Covid-19.

Background: Rheumatoid Arthritis (RA) has been associated with insulin resistance (IR), a well-established pathophysiological feature of Type 2 Diabetes (T2DM). Inconsistent literature evidence suggests that IR could be ameliorated by biological medications targeting TNFα. Objective: The aim of this systematic review was to evaluate the effect of TNFα inhibitors (TNFi) on IR in RA patients. Methods: We performed a systematic review in order to identify the available data on the effect of anti- TNFα medications on IR in RA patients. For this purpose, MedLine (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and SCOPUS were searched up to December 2016. Results: The search strategy retrieved 209 individual records. Of these, only 12 articles were included in the systematic review. The pooled analysis under a random-effects model demonstrated a significant improvement of IR after treatment with TNFi quantified with the HOmeostasis Model Assessment of Insulin Resistance (HOMA-IR), with a standardized difference in means (SDM) of -0.847 (95%CI: -1.278 - 0.417, p < 0.0001). Heterogeneity across studies was high (Q = 65.00 with df = 9, p < 0.001, I2 = 89.15%). Conclusion: Our meta-analysis suggests that TNFα blockade might improve IR in RA patients.

Purpose: To correlate rheumatologic with ophthalmic and laboratory findings in patients with rheumatoid arthritis (RA) to identify what effect these have on development of ocular disease. Methods: This is a cross-sectional study of 172 eyes of 86 patients with RA. Patients were examined by a group of rheumatologists. Sociodemographic, clinical, and laboratory data were collected. All patients underwent complete ophthalmologic examination including corneal topography and endothelial cell count. Results: There was no significant correlation between RA-negative prognostic indicators (NPIs) and pathologic corneal findings. Patients using disease-modifying antirheumatic drugs (DMARDs) and antimalarial drugs had greater corneal volumes (mean difference 8.51 mm3, 90% confidence interval [CI], 3.98-13.04, P = 0.004; and 2.24, 90% CI, 0.32-4.54, P = 0.048, respectively). Patients using azathioprine had lower endothelial cell counts compared with those using other drugs (mean difference 180 cells/mm2, 90% CI, 69-291, P = 0.008). Patients using biologic DMARDs had better tear osmolarity values (between 280 and 300 mOsm/L) than patients not using them (mean difference 14.3 mOsm/L, P = 0.022). There was no correlation between NPIs of RA and positive keratoconus screening indices (Spearman correlation OD -0.013, P = 0.91; OS -0.033, P = 0.76). Conclusions: There was no clear correlation between RA-NPIs and pathologic corneal findings in our study. DMARDs treatment may help maintain corneal integrity in our patients and prevented collagenolytic manifestations of RA. Other medications such as azathioprine should be used carefully, as endothelial damage may potentially occur. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Introduction: The majority of Psoriatic Arthritis patients experience a good clinical response to anti-Tumor Necrosis Factor (TNF)-α therapies. However, treatment failure with anti-TNF-α can represent a relevant clinical problem. Areas covered: We review the efficacy and safety profile of biological therapies that have been reported from randomized, controlled trials in phase II and phase III available in Pubmed Database for agents targeting IL-12/23p40 antibody (ustekinumab) and IL-17 (secukinumab), inhibitor of phosphodiesterase 4, (apremilast), and of JAK/STAT pathways (tofacitinib) and CTLA4 co-stimulation (abatacept) in Psoriatic Arthritis. Expert opinion: In Psoriatic Arthritis, main emerging drugs are represented by the fully human monoclonal IL-12/23p40 antibody, ustekinumab, the agent targeting IL-17, secukinumab, and the inhibitor of phosphodiesterase 4, apremilast. Results on T cell co-stimulation inhibition by abatacept are insufficient both in psoriasis and in PsA. In vitro investigations on JAK/STAT pathways in PsA suggest that tofacitinib could represent a further valuable therapeutic option. Emerging biological treatments other than anti-TNF agents, ustekinumab, secukinumab and apremilast appear promising for Psoriatic Arthritis and recent studies have showed a good efficacy and an acceptable safety profile; however, further and long-term studies are advocated

We read with interest the article by Gupta et al 1 who reported the management of treatments for rheumatic diseases during COVID-19 pandemic among practitioners in India. In this study, the authors showed that about half of the physicians would reduce the use of biological disease-modifying antirheumatic drugs (bDMARDs) or defer specific drugs such as rituximab.1 Choices were apparently made considering possible relationships between drug mechanism of action and effect on the viral infection.1 During COVID-19 pandemic, telemedicine is emerging as a possible tool for reducing the risk of contagion and viral spread,2–4 and a useful strategy for the management of chronic diseases.5 6 As of 29 April 2020, the outbreak of COVID-19 generated 201 505 confirmed cases in Italy, with 2405 confirmed cases in Naples Metropolitan area. The objective of our study was to evaluate telemedicine when offered as part of routine care for the follow-up of patients …

La artritis reumatoidea es una enfermedad crónica de carácter autoinmunitario caracterizada principalmente por el compromiso inflamatorio de las articulaciones cartilaginosas. Se han desarrollado múltiples tratamientos farmacológicos para controlar el avance de la artritis reumatoidea, entre ellos, los fármacos antirreumáticos modificadores de la enfermedad, además de nuevos esquemas terapéuticos con inhibidores del factor de necrosis tumoral alfa, con resultados clínicos satisfactorios. Sin embargo, el uso de tales medicamentos no resulta inocuo, ya que se los ha asociado con diversos efectos secundarios, especialmente, infecciones como la tuberculosis, lo cual exige la aplicación de pruebas de tamización antes de utilizarlos. Se reporta el caso de una paciente de 58 años de edad con artritis reumatoidea de seis años de evolución, que después de recibir tratamiento con uno de estos fármacos, el infliximab, desarrolló tuberculosis diseminada, cuyo diagnóstico se confirmó mediante radiología e histopatología. No se emplearon pruebas de detección de la tuberculosis latente antes de prescribirle el infliximab. Las pruebas de tamización para tuberculosis deben emplearse de forma rutinaria, con el fin de detectar aquellos pacientes con tuberculosis latente, ya que es la única manera de determinar si se requiere profilaxis antituberculosa antes de administrar dichos fármacos, hecho que marca la diferencia cuando se busca disminuir la incidencia de tuberculosis y la consecuente morbimortalid. Rheumatoid arthritis is an autoimmune systemic disease characterized mainly by inflammatory compromise of diarthrodial joints. Multiple drug therapies have been developed to control the activity of rheumatoid arthritis, among them, the first line of disease-modifying antirheumatic drugs (DMARD), and novel drug therapies such as the anti-TNF alpha therapy, with satisfactory clinical outcomes. Despite this positive fact, the use of this therapy implies the risk of producing negative effects due to its mechanism of action, which has been associated with multiple infections, especially tuberculosis, making it necessary to use screen tests before resorting to this kind of drugs. We present the case of a 58-year-old female patient, with a six-year history of rheumatoid arthritis. The patient developed disseminated tuberculosis with compatible radiological and histological findings after receiving treatment with infliximab (anti-TNF therapy). No test was performed to screen for latent tuberculosis infection prior to the administration of infliximab. The performance of routine screenings tests for tuberculosis prior to anti-TNF alpha therapy plays an essential role in the detection of asymptomatic patients with latent tuberculosis. This is the only way to identify those patients who would benefit from anti-tuberculosis drugs before the initiation of anti-TNF alpha therapy, which makes the difference in the search of a significant reduction in the incidence of tuberculosis and its associated morbidity and mortality. © Biomédica 2018.

Background Although in the past, prevention of the joint destruction and disability was strongly emphasised in Rheumatoid Arthritis (RA), at present, a growing body of evidence is focused at identifying the best management of associated comorbidities, such as Type 2 Diabetes (T2D). Recently, the hypothesis that blocking pro-inflammatory activity may be helpful in the treatment of some comorbidities has been proposed in RA patients. Objective We reviewed the role of IL-1β during RA and T2D, the efficacy of IL-1 blocking agents in controlling both diseases and, possible, decreasing the concomitant enhanced atherosclerotic process. Method After literature search, the available evidence has been selected and commented in the text. Results During RA, it is well known that different inflammatory cytokines, such as interleukin-1β (IL-1β), are pivotal pathogenic mediators and their role has been largely confirmed in clinical settings. Similarly, it has been shown that the excess of nutrients, secondary to over-nutrition, may activate the immune system, leading to an increased production of inflammatory cytokines, including IL-1β, suggesting new possible therapeutic targets. Conclusion Although further studies are needed to fully investigate the pathogenic interplay between inflammation and metabolic disorders, IL-1β has been implicated in both RA and T2D pathogenic mechanisms. Intriguingly, the potential role of anti-IL-1 drugs has been proposed in RA patients affected by T2D.

Rheumatoid arthritis (RA) is an immune-mediated condition which primarily affects the joints, but with critical extra-articular manifestations, including a significantly increased cardiovascular risk. Patients suffering from RA can develop deforming and disabling alterations of the affected joints. Their quality of life can be substantially affected, and their life expectancy is shorter compared to that of healthy subjects. Fortunately, several pathogenic mechanisms characterizing RA have been identified, leading to the development of targeted drugs. Inhibitors of tumor necrosis factor (TNF) were the first developed among biological medications and they dramatically changed the therapeutic perspectives of RA patients. Now, 20 years after the licensing of etanercept (the first anti-TNF drug), more than 10 different biological agents have been approved by the U.S. Food and Drug Administration (FDA). Additionally, more and more drugs are under investigation in clinical trials. This review will focus on the more recently approved monoclonal antibodies and the more promising antibodies under investigation.

Objective We aimed to evaluate the relationship among TNFα, sTNFR1, sTNFR2, sIL2R, IL6, neopterin and disease activity in ankylosing spondylitis (AS). Materials and methods TNFα, sTNFR1, sTNFR2, sIL2R, IL6 and neopterin were measured in patients and controls. Patients were grouped according to disease activity and medication. Results Neopterin and sTNFR1 were not different while TNFα, sTNFR2, sIL2R and IL6 were high in patients than controls. There was no difference between active and inactive patients for TNFα, sIL2R and IL6. sTNFR2 was significantly lower in active patients. There was no relationship between CRP positivity and disease activity. AS patient groups are; 1: TNF blockers, 2: nonsteroidal anti-inflammatory drugs (NSAIDs), 3: disease modifying anti-rheumatic drugs (DMARDs), 4: TNF blockers and NSAIDs, 5: DMARDs and NSAIDs. sTNFR2 was significantly lower in active patients than in inactive, in Group 1. ESR levels were significantly lower in inactive patients compared to active in group 3 and 4. There was no significant association between CRP positivity and disease activity. Conclusion According to our study, CRP is insufficient in evaluating AS disease activity. ESR can be useful in evaluating the disease activity. sTNFR2 might be useful as a biological indicator of disease activity in AS treated with TNF inhibitors alone.

We aim to draw attention to occult, atraumatic fractures of the odontoid process in patients with rheumatoid arthritis (RA) and to underline difficulties encountered during clinical and radiological diagnosis. A forty-seven years old man with RA for 4 years had occipital pain for 1 year without any history of trauma. Later, he developed weakness in the upper extremities, but he did not realize weakness in the lower extremities due to deformities. Contrast magnetic resonance imaging revealed a linear fracture of odontiod process and myelopathy. Cervical computed tomography scan revealed an old fracture border with separated and almost disappeared remnant of the tip of the odontoid without free particles in the cord. It was impossible to evaluate atlantoaxial and vertical subluxations with craniometric measurements due to destruction of the tip of odontoid. Following occipitocervical fusion and decompression and a rehabilitation program, his muscle strength improved; however, functional myelopathy stage did not change. Atraumatic fractures of the odontoid process may be more common than reported and may cause compression of the spinal cord or brain stem. Surgery is the treatment of choice but functional recovery is limited once neuronal damage has occurred. Erosion of the critical landmarks makes it difficult to diagnose and follow up atlantoaxial subluxation and/or vertical subluxation, therefore clinicians should consider radiographical follow-ups during the course of the disease. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd

Introduction Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX). Objectives To evaluate the efficacy and safety of RTX–MTX combination therapy compared with RTX alone in the treatment of RA. Methods We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed. Results We identified 338 RA patients, 162 treated with RTX and 176 with RTX–MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX–MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX + MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX + MTX and RTX, respectively; while 12 patients (4.5% in RTX + MTX, and 2.5% in RTX group) suspended therapy for AE. Conclusions RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.

Since the introduction of biologics, many concerns about the increased risk of infections have been reported and, to date, the real impact of infections on the daily practice in the rheumatologic centers is still largely unknown. In this work, we evaluated the infection rates associated with the use of biologics in a large cohort of patients. A prospective study, between January 2010 and December 2013, enrolling 731 rheumatic patients, was performed. Demographic and disease characteristics, therapies, comorbidities, and infectious events were recorded and statistically analyzed by multivariate analysis. Two-hundred thirty-five infectious episodes were observed in 28.4 % of patients. About total infections, bacteria were identified in 70.6 % of total cases and viruses in 18.3 %. The most common site of not-serious infection was the urinary tract. Duration of disease, longer follow-up, concomitant steroid therapy, and comorbidities were significantly associated with not-serious infection. In our cohort, 17 episodes fulfilled the criteria of serious infection and occurred in 17 different patients (2.3 %), the majority involving the lower respiratory tract. Serious infections were associated with the beginning of biologics in older age. Our prospective, observational study showed that, in daily practice, a lesser rate of serious as well as not-serious infections may be observed in rheumatic patients treated with biologics than those reported in previous papers. The most common sites of not-serious infections are both the urinary and the respiratory tracts, and for serious infections, the respiratory tract. When pathogens were isolated, we did not find any multidrug-resistant organism.

The prognosis for patients with rheumatoid arthritis or spondyloarthritides has improved dramatically due to earlier diagnosis, recognition of the need to treat early with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), alone or in combinations, the establishment of treatment targets, and the development of biological DMARDs (bDMARDs). Many patients are now able to achieve clinical remission or low disease activity with therapy, and reduce or eliminate systemic corticosteroid use. Guidelines recommend methotrexate as a first-line agent for the initial treatment of rheumatoid arthritis; however, a majority of patients will require a change of csDMARD or step up to combination therapy with the addition of another csDMARD or a bDMARD. However, treatment failure is common and switching to a different therapy may be required. The large number of available treatment options, combined with a lack of comparative data, makes the choice of a new therapy complex and often not evidence based. We summarize and discuss evidence to inform treatment decisions in patients who require a change in therapy, including baseline factors that may predict response to therapy.

Objectives This study aimed to evaluate whether the early achievement of clinical remission influences overall survival in an inception cohort of patients with inflammatory polyarthritis (IP). Methods Consecutive early IP patients, recruited to a primary care based inception cohort from 1990 to 1994 and from 2000 to 2004 were eligible for this study. Remission was defined as absence of clinically detectable joint inflammation on a 51-joint count. In sensitivity analyses, less stringent definitions of remission were used, based on 28-joint counts. Remission was assessed at 1, 2 and 3 years after baseline. All patients were flagged with the national death register. Censoring was set at 1 May 2011. The effect of remission on mortality was analysed using the Cox proportional hazard regression model, and presented as HRs and 95% CIs. Results A total of 1251 patients were included in the analyses. Having been in remission at least once within the first 3 years of follow-up was associated with a significantly lower risk of death: HR 0.72 (95% CI 0.55 to 0.94). Patients who were in remission 1 year after the baseline assessments and had persistent remission over time had the greatest reduction in mortality risk compared with patients who never achieved remission within the first 3 years of follow-up: HR 0.58 (95% CI 0.37 to 0.91). Remission according to less stringent definitions was associated with progressively lower protective effect. Conclusions Early and sustained remission is associated with decreased all-cause mortality in patients with IP. This result supports clinical remission as the target in the management of IP.

Emphysematous aortitis is a form of septic aortitis. It is a rare disease with a high mortality rate, necessitating prompt diagnosis and aggressive treatment. We present the computed tomography features of emphysematous aortitis leading to esophageal rupture and esophageal-pleural fistula in a 76-year-old female with rheumatoid arthritis. © SAGE Publications.

Çalışmada 24 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır. In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.

Background: Data from routine clinical practice are needed to further define the efficacy and safety of biologic medications in children with juvenile idiopathic arthritis (JIA). The aim of this analysis was to investigate the disease status, reasons for discontinuation and adverse events in Italian JIA patients treated with etanercept (ETN). Methods: In 2013, all centers of the Italian Pediatric Rheumatology Study Group were asked to make a census of patients given ETN after January 2000. Patients were classified in three groups: group 1 = patients still taking ETN; group 2 = patients discontinued from ETN for any reasons; group 3 = patients lost to follow-up while receiving ETN. All three groups received a retrospective assessment; patients in group 1 also underwent a cross-sectional assessment. Results: 1038 patients were enrolled by 23 centers: 422 (40.7%) were in group 1, 462 (44.5%) in group 2, and 154 (14.8%) in group 3. Median duration of ETN therapy was 2.5 years. At cross-sectional assessment, 41.8% to 48.6% of patients in group 1 met formal criteria for inactive disease, whereas 52.4% of patients in group 2 and 55.8% of patients in group 3 were judged in clinical remission by their caring physician at last visit. A relatively greater proportion of patients with systemic arthritis were discontinued or lost to follow-up. Parent evaluations at cross-sectional visit in group 1 showed that 52.4% of patients had normal physical function, very few had impairment in quality of life, 51.2% had no pain, 76% had no morning stiffness, and 82.7% of parents were satisfied with their child's illness outcome. Clinically significant adverse events were reported for 27.8% of patients and ETN was discontinued for side effects in 9.5%. The most common adverse events were new onset or recurrent uveitis (10.2%), infections (6.6%), injection site reactions (4.4%), and neuropsychiatric (3.1%), gastrointestinal (2.4%), and hematological disorders (2.1%). Ten patients developed an inflammatory bowel disease and 2 had a malignancy. One patient died of a fulminant streptococcal sepsis. Conclusions: Around half of the patients achieved complete disease quiescence under treatment with ETN. The medication was overall well tolerated, as only one quarter of patients experienced clinically significant adverse events and less than 10% had treatment discontinued for toxicity.

Objective.Screening strategies for latent tuberculosis (TB) before starting tumor necrosis factor (TNF)-α inhibitors have decreased the prevalence of TB among patients who are treated with these agents. However, despite vigilant screening, TB continues to be an important problem, especially in parts of the world with a high background TB prevalence. The aim of this study was to determine the factors related to TB among a large multicenter cohort of patients who were treated with anti-TNF.Methods.Fifteen rheumatology centers participated in this study. Among the 10,434 patients who were treated with anti-TNF between September 2002 and September 2012, 73 (0.69%) had developed TB. We described the demographic features and disease characteristics of these 73 patients and compared them to 7695 patients who were treated with anti-TNF, did not develop TB, and had complete data available.Results.Among the 73 patients diagnosed with TB (39 men, 34 women, mean age 43.6 ± 13 yrs), the most frequent diagnoses were ankylosing spondylitis (n = 38) and rheumatoid arthritis (n = 25). More than half of the patients had extrapulmonary TB (39/73, 53%). Six patients died (8.2%). In the logistic regression model, types of anti-TNF drugs [infliximab (IFX), OR 3.4, 95% CI 1.88–6.10, p = 0.001] and insufficient and irregular isoniazid use (< 9 mos; OR 3.15, 95% CI 1.43–6.9, p = 0.004) were independent predictors of TB development.Conclusion.Our results suggest that TB is an important complication of anti-TNF therapies in Turkey. TB chemoprophylaxis less than 9 months and the use of IFX therapy were independent risk factors for TB development.

Summary Aim While the introduction of the treat-to-target (T2T) strategy has been an important advance in the management of rheumatoid arthritis (RA), the potential for increased toxicity due to use of concurrent drugs could adversely affect patient reported outcomes (PROs). The objective was to determine whether the cessation of therapy due to toxicity affects long-term improvement in PROs in patients treated according to T2T strategy. Methods A total of 149 patients from an inception cohort of early RA were included. The occurrence and severity of toxicity were monitored at each visit over 3 years. PROs studied were function (measured using health assessment questionnaire); pain, fatigue and patient global assessment (PtGA) all assessed using a 100 mm visual analogue scale; helplessness and health-related quality of life (HRQoL). For each PRO, effect of drug withdrawal was measured by comparing mean change in PROs among patients with no/temporary vs. permanent withdrawal. In addition, effects of frequency of drug withdrawals, weeks to withdrawal and number of drugs withdrawn were analysed using linear regression. Result After 3 years, 56 (37.4%) patients ceased at least one drug permanently due to toxicity. Patients with no/temporary withdrawal (n = 93) achieved significantly greater improvement in function (mean change = −0.54 vs. −0.31, p = 0.033), pain (mean change = −39.82 vs. −5.02, p = 0.018), fatigue (mean change = −29.14 vs. −14.76, p = 0.015) and PtGA (mean change = −29.64 vs. −17.00, p = 0.018) compared with their counterparts. Higher frequency of withdrawals was associated with lesser improvements in function, pain, fatigue and PtGA, while the number of drugs withdrawn and the weeks to withdrawal had lesser effects. However, the cessation of the drugs due to their toxicity did not have a significant association with HRQoL and helplessness. Conclusion Improvements in function, pain, fatigue and PtGA at 3 years were diminished for patients who ceased drugs due to toxicity while broader measures of HRQoL were not affected.

Objectives: To test the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and disease activity score in 44 and 28 joints (DAS, DAS28) definitions of remission in early rheumatoid arthritis (RA), against disability and ultrasound-detectable synovitis. Methods: In an observational study of early RA patients, remission rates were determined and compared in 166 patients. The remission definitions included the simplified disease activity index (SDAI≤3.3), ACR/EULAR (categorical), DAS28 (

Objective— Subjects with psoriatic arthritis (PsA) have an abnormally high prevalence of vascular risk factors (VRFs) and are predisposed to vascular mortality. Tumor necrosis factor (TNF)-α, a major determinant of inflammation, is involved in atherosclerosis. Ultrasonographic carotid intima-media thickness (C-IMT) evaluation allows for subclinical atherosclerosis detection. Methods and Results— Two hundred twenty-four PsA patients (120 on TNF-α blockers and 104 on traditional disease-modifying antirheumatic drugs [DMARDs]) underwent a C-IMT ultrasound assessment. As many as 305 matched subjects without any inflammatory/rheumatologic disease served as controls. The C-IMT of PsA subjects without VRFs was higher ( P P P P P P =0.313). Conclusion— Among PsA individuals, the C-IMT is higher in subjects on DMARDs than in those on TNF-α blockers. The reduction of inflammation may hamper the cascade that causes the raised vascular risk in PsA patients.

Objective:To investigate the role of the HS1,2 enhancer polymorphisms as a new candidate marker for rheumatoid arthritis (RA) and to define the possible association with autoantibody positivity and clinical outcome.Methods:Genomic DNA was obtained from two cohorts of patients with RA (100 with early RA (ERA) and 114 with longstanding RA (LSRA)) and from 248 gender-matched controls from the same geographical area. Clinical and immunological characteristics were recorded for all the patients.Results:The percentage of the 2/2 genotype was higher in patients with ERA (27.0%), and in patients with LSRA (34.2%), than in controls (14.9%) (ERA: OR = 2.11 (95% CI 1.20 to 3.70) vs controls; LSRA: OR = 2.96 (95% CI 1.76 to 5.00) vs controls). A lower representation of allele *3 was present in patients with ERA (2.0%) than in controls (6.0%; OR = 0.32 (95% CI 0.11 to 0.91)). No significant associations were found between polymorphisms and autoantibodies positivity.Conclusion:The HS1,2A allele *2 associates with early and longstanding RA.

Objective To evaluate the efficacy and safety in the long term of a retreatment regimen with Rituximab (RTX) alone administered at clinical relapse in cryoglobulinemic vasculitis (CV). Methods Thirty patients with severe HCV-related CV, previously enrolled in the multicentre Italian trial on RTX in the treatment of CV, were retrospectively evaluated after the end of the trial. All of them were managed with RTX alone at clinical relapse, if any. Disease activity at the last available follow up was defined as complete remission (absence of active disease), partial remission (response > 50% of at least one manifestation among glomerulonephritis, peripheral neuropathy or skin ulcers) or active disease. Results The mean follow up after the first RTX cycle was 72.6 (20.4) months. After the end of the trial, 21/30 (70%) patients showed an active follow up [81.7 (10.9) months)], 3/30 (10%) lost follow up and 6/30 (20%) died. 12/21 (57.1%) patients were in complete disease remission, 5/21 (23.8%) showed a partial response and 4/21 (19%) had an active disease. 17/30 (56.7%) patients needed retreatment for relapse with a mean time to retreatment of 22.3 (12.1) months. Treatment survival of this regimen was 7.6 (0.3) years. Recurrent non-severe infections occurred in 3/30, with chronic hypogammaglobulinemia in 2/3 patients. Conclusions A long-term regimen of retreatment with RTX alone given at clinical relapse seems to be effective and safe in CV, with a low rate of infections and severe hypogammaglobulinemia.

Item does not contain fulltext The inflammatory cytokines IL-1alpha and IL-1beta orchestrate local and systemic inflammatory responses underlying a broad spectrum of diseases. Three agents for reducing IL-1 activities are currently available. Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist. Anakinra binds to the IL-1 receptor and prevents the activity of IL-1alpha and IL-1beta. The soluble decoy receptor rilonacept and the neutralizing mAb canakinumab block IL-1beta. A mAb directed against the IL-1 receptor and a neutralizing anti-human IL-1alpha are in clinical trials. The availability of therapies specifically targeting IL-1 unveiled the pathological role of IL-1-mediated inflammation in a broadening list of diseases. Conditions effectively treated with agents blocking IL-1 range from classic rheumatic diseases, such as RA and gout, to autoinflammatory syndromes, such as systemic JIA and FMF. However, IL-1 antagonism is also effective against highly prevalent inflammatory diseases, namely cardiovascular diseases and type 2 diabetes, conditions that are frequently encountered as co-morbidities in patients with rheumatic diseases. Thereby, IL-1 inhibition has the potential to lift the burden of disease for patients with rheumatic conditions, but also to provide clinical benefits beyond the efficacy on osteoarticular manifestations.

Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting peripheral and axial joints, usually associated with psoriasis (PsO) and involving various systems and organs (eye inflammation, such as uveitis; and involvement of nail and enthesis), and it usually requires a multidisciplinary treatment approach. Tumor necrosis factor-α (TNF-α) is overexpressed in psoriatic synovium and skin plaques and its selective inhibition by anti-TNF-α agents has been demonstrated to reduce TNF-α levels in the articular environment, reversing the synovial hyperproliferative phenotype. Studies performed on anti-TNF-α agents in PsA demonstrated that they are able to reduce neutrophil and macrophage infiltration as well as vascular cell adhesion protein 1 expression with ensuing synovial thickness normalization. The efficacy of anti-TNF-α agents for all PsA manifestations (peripheral arthritis, axial involvement, enthesopathy, and skin disease) suggests that anti-TNF-α efficacy might be related to the ability to influence angiogenesis and osteoclastogenesis, reduce synovial inflammation, and slow radiological disease progression. This review describes the role of anti-TNF-α in each manifestation of PsA.

Psoriatic arthritis (PsA) is a chronic inflammatory condition involving the spine, enthesis and peripheral joints, which is associated with psoriasis. PsA therapy varies from use of NSAIDs to disease-modifying anti-rheumatic agents (DMARDs). However, their use can represent a limitation in patients with concomitant hepatitis C virus (HCV) infection. In the last few decades, anti-TNF-α therapy has opened new horizons in the treatment of PsA. Hence, the purpose of this review is to explore the efficacy and safety of anti-TNF-α agents in PsA and concomitant HCV infection.We reviewed the available medical literature to find all cases of PsA and concomitant HCV infection treated with TNF-α inhibitors. We found a total of 38 cases of patients with PsA and concomitant HCV infection in therapy with anti-TNF-α agents.The available literature, summarized in this review, still remains very limited. Data suggest that therapy with the anti-TNF-α agents, mainly etanercept and adalimumab, at least with short-term use, would appear efficacious and reasonably safe in the management of PsA patients with concomitant HCV infection. With regard to infliximab, efficacy and safety have been scarcely explored, whereas in the case of golimumab and certolizumab no report was found, may be due to their recent introduction on the market.

Psoriatic arthritis (PsA) is a systemic inflammatory disease characterized by possible peripheral and axial joint involvement, enthesitis, dactylitis, and skin and nail disease. It affects up to one-third of psoriatic patients, and may be associated with comorbidities such as cardiovascular and metabolic diseases. The usually prescribed initial treatment of moderate-severe PsA is methotrexate, which may be accompanied or replaced by a tumor necrosis factor (TNF) inhibitor such as etanercept, infliximab, or adalimumab. However, some patients may become unresponsive (or have contraindications) to available anti-TNF agents and require alternative treatment. The aim of this review is to describe the potential role of some new immunomodulatory agents.

Background Eumusc.net (http://www.eumusc.net) is a European project supported by the EU and European League Against Rheumatism to improve musculoskeletal care in Europe. Objective To develop patient-centred healthcare quality indicators (HCQIs) for healthcare provision for rheumatoid arthritis (RA) patients. Methods Based on a systematic literature search, existing HCQIs for RA were identified and their contents analysed and categorised referring to a list of 16 standards of care developed within the eumusc.net. An international expert panel comprising 14 healthcare providers and two patient representatives added topics and during repeated Delphi processes by email ranked the topics and rephrased suggested HCQIs with the preliminary set being established during a second expert group meeting. After an audit process by rheumatology units (including academic centres) in six countries (The Netherlands, Norway, Romania, Italy, Austria and Sweden), a final version of the HCQIs was established. Results 56 possible topics for HCQIs were processed resulting in a final set of HCQIs for RA (n=14) including two for structure (patient information and calculation of composite scores), 11 for process (eg, access to care, assessments, and pharmacological and non-pharmacological treatments) and one for outcome (effect of treatment on disease activity). They included definitions to be used in clinical practice and also by patients. Further, the numerators and the denominators for each HCQI were defined. Conclusions A set of 14 patient-centred HCQIs for RA was developed to be used in quality improvement and bench marking in countries across Europe.

Background Identification of parameters for early diagnosis and treatment response would be beneficial for patients with early rheumatoid arthritis (ERA) to prevent ongoing joint damage. miRNAs have features of potential biomarkers, and an altered expression of miRNAs was shown in established rheumatoid arthritis (RA). Objective To analyse RA associated miRNAs in the sera of patients with ERA to find markers of early disease, clinical activity or predictors of disease outcome. Methods Total RNA was isolated from whole sera in ERA patients (prior to and after 3 and 12 months of therapy with disease modifying antirheumatic drugs), in patients with established RA and in healthy controls (HC) using phenol–chloroform extraction. Expression of miR-146a, miR-155, miR-223, miR-16, miR-203, miR-132 and miR-124a was analysed by TaqMan Real Time PCR. Results From all analysed miRNAs, levels of miR-146a, miR-155 and miR-16 were decreased in the sera of ERA patients in comparison with established RA. A change in circulating miR-16 in the first 3 months of therapy was associated with a decrease in DAS28 in long term follow-up in ERA (p=0.002). Levels of circulating miR-223 in treatment naive ERA correlated with C reactive protein (p=0.008), DAS28 (p=0.031) and change in DAS28 after 3 months (p=0.003) and 12 months (p=0.011) of follow-up. However, neither miR-16 nor miR-223 could distinguish ERA from HC. Conclusions Differential expression of circulating miR-146a, miR-155 and miR-16 in the sera of ERA patients may characterise an early stage of the disease. We suggest miR-223 as a marker of disease activity and miR-16 and miR-223 as possible predictors for disease outcome in ERA.

WOS: 000344362300007, PubMed ID: 24433553, Objectives: Paraneoplastic arthritis (PA) may mimic rheumatic diseases. While presenting the demographic and laboratory features of the patients diagnosed with PA, this study also aims to provide possible appropriate tools to differentiate the PA cases from early rheumatoid arthritis (ERA). Methods: Sixty-five patients with PA (male/female: 43/22) from 15 different rheumatology clinics and 50 consecutive patients with ERA (male/female: 13/37) fulfilling the 2010 American College of Rheumatology (ACR) criteria for the diagnosis if the RA from Gaziantep Rheumatology Early Arthritis Trial (GREAT) as controls who were diagnosed at least 12 months before, were enrolled into study. Results: Mean ages of the patients with PA and ERA were 50.2 +/- 15.3, and 42.7 +/- 12.3, respectively, and the mean ages of the patients with PA were significantly higher than the ERA. Unlike the ERA patients, in our case series PA was predominantly observed among males. Oligoarthritis was significantly higher in solid tumors in contrast to ERA (P = 0.001). Polyarthritis and symmetric arthritis were significantly higher in the ERA group in contrast to all malignancies (P = 0.001). Rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) positivity were significantly higher in the ERA group (each P = 0.001). Lactic dehydrogenase levels of hematologic malignancies were significantly higher than other groups (each, P = 0.001). Conclusions: ERA patients had more symmetric joint involvement than PA; laboratory markers could be also an alternative where there is high RF and anti-CCP positivity with antibody levels among the ERA patients. Finally, the demographic features can be used as differentiating

Purulent pericarditis in rheumatoid arthritis treated with rituximab and methotrexate.

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α, in addition to its pro-inflammatory role, is an essential cytokine for the host's defense, and its depletion by treatment may facilitate the risk of viral infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in PsA patients with concurrent hepatitis C virus (HCV) infection. This is a multicenter study carried out in four Italian centers specialized in the diagnosis and treatment of PsA. At baseline and after 6 (T6) and 12 months (T12) of therapy, data concerning PsA activity and liver tests were registered. A total of 15 PsA patients with concomitant HCV infection were included in the study. At baseline, 13 patients had low viral load, and liver enzyme tests were within the normal range. During the observation period, these values remained stable. On the other hand, at baseline, a high viral load with slightly increased values of AST and ALT was detected in one patient. At T6 and T12, these values decreased. The remaining patient, at baseline, had low viral load, but with slightly increased AST and ALT values that normalized during the observation period. This is the greatest sample size available in the literature on this topic. The data suggests that anti-TNF-α agents are effective and safe in PsA patients with concomitant HCV. We suggest that the use of anti-TNF-α agents, accompanied by close monitoring, could be a therapeutic option.

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

Discoid lupus erythematosus (DLE) is a chronic autoimmune skin disorder, typically characterized by well-defined erythematous lesions with thick adherent scales and follicular plugging. It usually affects photo-exposed skin, particularly on the scalp, forehead and cheeks. Isolated eyelid involvement is uncommon and frequently lacks the typical clinical morphologic findings, imposing a diagnostic challenge and a potential delay in the provision of therapy

Objective.The study aim was to determine treatment persistence rates and to identify causes of discontinuation in psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients in clinical practice.Methods.Patients treated with adalimumab (ADA), etanercept (ETA), or infliximab (INF) were retrospectively included. Treatment persistence rates were analyzed by means of a stepwise logistic regression. Differences between therapy duration were assessed by means of an analysis of variance model (ANOVA), while a chi-square test was used to evaluate relationships between therapies and causes of treatment discontinuation and the administration of concomitant disease-modifying antirheumatic drugs (DMARDs) among therapies and types of disease considering completed courses of therapy versus courses that were discontinued.Results.268 patients received a total of 353 anti-TNF treatment courses (97 ADA, 180 ETA, and 76 INF). Comparison among therapies showed significant difference regarding the treatment persistence rates due to the contrast between ETA and INF (P=0.0062). We observed that 84.7% of patients were still responding after 6 months of follow-up. Comparison among diseases showed that there were significant differences between PsA and AS (P=0.0073) and PsA and PsA with predominant axial involvement (P=0.0467) in terms of duration of the therapy, while there were no significant differences with regard to the persistence rate.Conclusions.In this cohort, anti-TNF-αtherapy was associated with high drug persistence rates. As in rheumatoid arthritis, switching to another anti-TNF-αagent can be an effective option when, during the treatment of AS or PsA, therapy is suspended because of inefficacy or an adverse event. Combination therapy with DMARDs was associated with a better persistence rate.

Objective: The primary objective of this retrospective study was to investigate the possibility of achieving partial remission (PR) in AS patients treated with anti-TNF-α antagonists, such as adalimumab (ADA), etanercept (ETA) and infliximab (INF), in a real clinical practice setting. Predictors of PR were also evaluated. Methods: A retrospective study was conducted in patients with AS treated with ADA, ETA and INF from 2000 to 2012. Kaplan-Meier survival curves were plotted to determine the rates of PR during the treatment with anti-TNF-α drugs. Results: A total of 283 patients with AS were treated with ADA (18.7%), ETA (26.8%) and INF (54.4%) as first anti-TNF-α drugs, with a PR rate of 57.6%. The probability of obtaining PR with ADA, ETA or INF was not significantly different among all anti-TNF-α patients. AS patients treated with a second anti-TNF-α drug had a PR rate of 40.5%, but after switching for lack of response, the probability of obtaining PR with a second anti-TNF-α drug was significantly lower from that of the first anti-TNF-α drug (P = 0.0039). The probability of obtaining PR in patients with enthesitis (P = 0.04) or psoriasis (P = 0.0016) or low levels of CRP (P = 0.0225) was significantly lower compared with that of patients without these manifestations at baseline. Conclusion: Our real-life study on PR confirmed the effectiveness of ADA, ETA or INF as first or second anti-TNF-α drugs. The presence at baseline of enthesitis or psoriasis or low CRP values yielded a lower probability of obtaining PR. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Item does not contain fulltext The study objective was to report treatment with an interleukin (IL)-1 receptor antagonist, anakinra, in patients with multiorgan Behcet's disease (BD). Comparison of clinical manifestations, previous treatments, markers of inflammation, concomitant medications, treatment regimen modifications, relapses, and adverse events before and during anakinra administration among patients with BD were evaluated. Nine BD patients (mean age 34.55 +/- 16.30 years) refractory to tumor necrosis factor blockers and standardized therapies are reported in our survey. Their mean age at disease onset was 25 +/- 13.88 years and their overall disease duration was 9.55 +/- 5.33 years. All patients were positive for the HLA-B51 allele. Within 1 or 2 weeks following the initiation of anakinra, eight out of nine patients promptly responded, and most of them were maintained on 100 mg of daily anakinra with low doses of prednisone. However, most patients experienced a relapse in one or more clinical manifestations over time (mean time to relapse 29 +/- 21.65 weeks), and only one patient remained completely under control on anakinra monotherapy. Despite a relapse in one or more disease manifestations, treatment was continued in most patients for a mean period of 13.75 +/- 6.49 months. No serious adverse events occurred. Eight out of nine refractory BD patients showed a prompt improvement after starting anakinra, supporting the concept that IL-1 plays a pathological role in this disease. Nevertheless, after several months, most patients experienced a relapse. It remains unclear whether increasing the dose of anakinra would have prevented the reoccurrence of disease activity.

Psoriatic arthritis (PsA) is a chronic inflammatory condition, characterized by an excess of metabolic disorders. Metabolic syndrome (MetS) is a cluster of classic cardiovascular risk factors, due to an imbalance between pro- and anti-inflammatory adipokines. Tumor necrosis factor (TNF)-α is a pro-inflammatory adipocytokine mainly produced by monocytes and macrophages with a central role in inflammatory responses, but it also induces adipocytes apoptosis, promotes insulin resistance, and stimulates lipolysis. The aim of this study was to evaluate the impact of therapy with etanercept (ETN), adalimumab (ADA), and methotrexate (MTX) on MetS components in a cohort of PsA patients with a follow-up period of 24 months. A retrospective study has been conducted in a cohort of PsA patients. On the basis of the inclusion criteria, we identified the first 70 consecutive patients, respectively, on ADA, ETN, and MTX, for a total of 210 patients achieving PsARC criteria during the observation period. As part of the routine clinical practice, assessment of metabolic parameters and of disease activity was recorded at baseline (T0), at 12 months (T1), and at 24 months (T2). The results show that when the specific components of the MetS were considered, taking also into account by regression analysis the effect of the confounding factors, the patients on etN and ADA show a significant improvement of the metabolic syndrome components (in detail, waist circumference, triglycerides, high-density lipoprotein cholesterol, and glucose) as compared to the MTX group. In conclusion, these data suggest that the biologic treatment in PsA can no longer be taken into consideration only for its positive effect on articular and cutaneous symptoms but also on the various aspects of this complex picture.

Objectives: To evaluate the performance of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 classification criteria for rheumatoid arthritis (RA) with a systematic literature review and a meta-analysis. Methods: PubMed, Embase, Cochrane Library and the abstracts of the ACR and EULAR meetings (2010-2012) were searched for original articles or abstracts with the following inclusion criteria: 1) recent onset arthritis, with at least one swollen joint and no alternative diagnosis; 2) the ACR/EULAR 2010 criteria as index test; 3) the prescription of methotrexate (MTX) or disease modifying antirheumatic drugs (DMARDs) at any time during follow-up as reference standard. Data were pooled using the bivariate model. Three meta-analyses were performed with MTX (primary analysis), DMARDs or their combination (secondary analyses) as reference standard. Heterogeneity was formally tested and explored performing an influence analysis. Results: The search identified 1,277 references. Six full papers and 4 abstracts met the inclusion criteria. With MTX as reference standard, sensitivity (95% confidence interval, CI) was 0.80 (0.74,0.85), specificity 0.61 (0.56,0.67), positive likelihood ratio (LR) 2.11 (1.92,2.32), negative LR 0.31 (0.25,0.38) and the diagnostic odds ratio (DOR) was 6.74 (5.49,8.28). Using DMARDs as reference standard, sensitivity was 0.73 (0.64,0.80), specificity was 0.74 (0.68,0.79), LR+2.85 (2.53,3.22), LR- 0.35 (0.27,0.45) and DOR 8.03 (6.4,10.09). Using the combination of MTX and DMARDs as reference standard, intermediate results were obtained. The influence analysis detected one potentially influential study. However, its exclusion from the meta-analysis did not have a clinically relevant impact on the results. Conclusions: The new classification criteria have good sensitivity, lower specificity and an overall moderate diagnostic accuracy. These results confirm that the criteria have classificative and not diagnostic function. © 2013 Sakellariou et al.

The signs and symptoms of ankylosing spondylitis (AS) respond inadequately to nonsteroidal antiinflammatory drugs, corticosteroids, and disease modifying antirheumatic drugs in quite a number of patients. Tumor necrosis factor inhibitors have demonstrated to be of value in reducing AS disease activity in clinical trials. The efficacy and safety of both etanercept and infliximab in patients with ankylosing spondylitis were compared in a 2-year open label randomised study. Our results are consistent with a significant more rapid clinical improvement in the infliximab treated group. Treatment with both etanercept and infliximab at the end of the study was effective, safe, and well tolerated. © 2009 Springer-Verlag.

Objectives. This study aimed to evaluate the usefulness of a systematic musculoskeletal ultrasonographic (US) assessment in the detection of residual disease activity in patients with early RA who achieved clinical remission. Methods. We prospectively studied 106 early RA patients receiving conventional DMARDs according to a disease activity score (DAS)-steered therapeutic protocol over a 24-month period. Standard evaluation included clinical, laboratory, functional and systematic (44 joints) US assessment. US indexes of grey scale (GS) and power Doppler (PD) synovitis were correlated with clinical evaluation, laboratory indexes and clinical outcome. Clinical remission was defined when DAS was < 1 .6 at two consecutive visits 3 months apart. Results. US examination was significantly more sensitive than clinical examination, both in active disease and in remission. In patients with an active disease, both clinical and US indexes correlated with CRP, whereas in remission only PD still remained significantly correlated. In clinical remission, 95% of the patients showed residual GS synovitis, and 41% of them showed a positive PD signal. Positive PD signal, even in a single joint, resulted the main predictor of relapse within 6 months, both in univariable and multivariable logistic regression analysis. Conclusions. In a cohort of early RA patients treated with conventional DMARDs, US-GS can detect residual disease activity more sensitively than clinical examination both in active disease and in remission. Moreover, PD-positive synovial hypertrophy identifies an ongoing inflammation even during remission and predicts short-term relapse.