Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present ...European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD).
The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement.
Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined.
These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.
Objectives
Literature data suggest a significantly higher mortality in patients affected by systemic lupus erythematosus (SLE) developing chronic damage. Therefore, damage prevention is a major goal ...in the management of SLE patients. In the present study, we assessed damage by means of the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI), in a large cohort of SLE patients. Additionally, we aimed at evaluating its association with demographic and clinical features as well as with disease activity and laboratory findings.
Patients and methods
We enrolled consecutive patients affected by SLE diagnosed according to the American College of Rheumatology (ACR) 1997 revised criteria. Chronic damage was determined by SDI calculated at the last examination in all patients with at least six months of follow-up. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K); flare was defined as an increase of SLEDAI-2K ≥ 4 compared with the previous visit.
Results
We evaluated 349 SLE patients (M/F 25/324, mean age ± SD 42.7 ± 12.4 years, mean disease duration ± SD 164.9 ± 105.2 months). Among the enrolled patients, 125 (35.8%) showed a SDI ≥ 1 (mean SDI ± SD 1.7 ± 0.9, range 0–5). The musculo-skeletal was the most frequently involved organ/system in SDI score (41/349 patients, 11.7%), with deforming/erosive arthritis in 21/349 (6.0%). The presence of chronic damage was associated with age (P < 0.001), disease duration (P < 0.001), number of flares (P = 0.02) and with the use of glucocorticoids (P = 0.02). The logistic regression analysis revealed the association between neuropsychiatric damage and antiphospholipid syndrome (P = 0.01, OR = 3.9) and between the presence of cardiovascular damage and anti-β2GPI antibodies (P = 0.01, OR 6.2).
Conclusions
In the present study chronic damage was identified in about one third of SLE patients. The association between SDI and the number of flares claim for a thigh-control of the disease activity in order to prevent the chronic damage. The possible role of antiphospholipid antibodies (aPL) in the development of neuropsychiatric and cardiovascular damage may suggest a more careful assessment of such aPL positive patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Objective
Systemic autoimmune diseases, in particular systemic lupus erythematosus and rheumatoid arthritis, are characterized by a high risk of premature cardiovascular (CV) events. Disease‐related ...characteristics and traditional CV disease risk factors may contribute to atherosclerotic damage. However, there are limited data on the risk of overt CV events in primary Sjögren's syndrome (pSS).
Methods
We retrospectively analysed a cohort of patients with 1343 pSS. Disease‐related clinical and laboratory data, traditional CV disease risk factors and overt CV events were recorded. Prevalence of traditional CV disease risk factors and of major CV events was compared between a subgroup of 788 female patients with pSS aged from 35 to 74 years and 4774 age‐matched healthy women.
Results
Hypertension and hypercholesterolaemia were more prevalent, whereas smoking, obesity and diabetes mellitus were less prevalent, in women with pSS than in control subjects. Cerebrovascular events (2.5% vs. 1.4%, P = 0.005) and myocardial infarction (MI) (1.0% vs. 0.4%, P = 0.002) were more common in patients with pSS. In the whole population, central nervous system involvement (odds ratio (OR) 5.6, 95% confidence interval (CI) 1.35–23.7, P = 0.02) and use of immunosuppressive therapy (OR 1.9, 95% CI 1.04–3.70, P = 0.04) were associated with a higher risk of CV events. Patients with leucopenia had a higher risk of angina (P = 0.01).
Conclusions
pSS is associated with an increased risk of cerebrovascular events and MI. Disease‐related clinical and immunological markers may have a role in promoting CV events.
Autophagy has emerged as a key mechanism in the survival and function of T and B lymphocytes, and its activation was involved in apoptosis resistance in rheumatoid arthritis (RA). To investigate ...whether the relationship between autophagy and apoptosis may impact the response to the therapy, we analyzed ex vivo spontaneous autophagy and apoptosis in patients with RA subjected to treatment with anti-tumor necrosis factor (TNF) drugs and in vitro the effects of TNFα and anti-TNF drugs on cell fate.
Peripheral blood mononuclear cells (PBMCs) from 25 RA patients treated with anti-TNF drugs were analyzed for levels of autophagy marker LC3-II by western blot and for the percentage of annexin V-positive apoptotic cells by flow cytometry. The same techniques were used to assess autophagy and apoptosis after in vitro treatment with TNFα and etanercept in both PBMCs and fibroblast-like synoviocytes (FLS) from patients with RA.
PBMCs from patients with RA responsive to treatment showed a significant reduction in LC3-II levels, associated with an increased apoptotic activation after 4 months of therapy with anti-TNF drugs. Additionally, the expression of LC3-II correlated with DAS28. TNFα was able to induce autophagy in a dose-dependent manner after 24 h of culture in RA PBMCs and FLS. Moreover, etanercept caused a significant reduction of autophagy and of levels of citrullinated proteins.
Our results show how the crosstalk between autophagy and apoptosis can sustain the survival of immune cells, thus influencing RA progression. This suggests that inhibition of autophagy represents a possible therapeutic target in RA.
To develop evidence-based European League Against Rheumatism (EULAR) recommendations for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD).
A EULAR task force was ...composed of experts representing 11 European countries, consisting of eight rheumatologists, four clinical immunologists, one rheumatologist/clinical immunologist, one infectious disease physician, one nephrologist, one paediatrician/rheumatologist and one clinical epidemiologist. Key questions were formulated and the eligible spectrum of AIIRD, immunosuppressive drugs and vaccines were defined in order to perform a systematic literature review. A search was made of Medline from 1966 to October 2009 as well as abstracts from the EULAR meetings of 2008 and 2009 and the American College of Rheumatology (ACR) meetings of 2007 and 2008. Evidence was graded in categories I-IV, the strength of recommendations was graded in categories A-D and Delphi voting was applied to determine the level of agreement between the experts of the task force.
Eight key questions and 13 recommendations addressing vaccination in patients with AIIRD were formulated. The strength of each recommendation was determined. Delphi voting revealed a very high level of agreement with the recommendations among the experts of the task force. Finally, a research agenda was proposed.
Recommendations for vaccination in patients with AIIRD based on the currently available evidence and expert opinion were formulated. More research is needed, particularly regarding the incidence of vaccine-preventable infectious diseases and the safety of vaccination in patients with AIIRD.
Summary
The aim of this study was to investigate the expression of the interleukin (IL)‐36 axis in patients with primary Sjögren's syndrome (pSS). Blood and minor labial salivary glands (MSG) ...biopsies were obtained from 35 pSS and 20 non‐Sjögren's syndrome patients (nSS) patients. Serum IL‐36α was assayed by enzyme‐linked immunosorbent assay (ELISA). IL‐36α, IL‐36R, IL‐36RA, IL‐38, IL‐22, IL‐17, IL‐23p19 and expression in MSGs was assessed by reverse transcription–polymerase chain reaction (RT–PCR), and tissue IL‐36α and IL‐38 expression was also investigated by immunohistochemistry (IHC). αβ and γδ T cells and CD68+ cells isolated from MSGs were also studied by flow cytometry and confocal microscopy analysis. IL‐36α was over‐expressed significantly in the serum and in the salivary glands of pSS. Salivary gland IL‐36α expression was correlated with the expression levels of IL‐17, IL‐22 and IL‐23p19. IL‐38, that acts as inhibitor of IL‐36α, was also up‐regulated in pSS. αβ+ CD3+ T cells and CD68+ cells were the major source of IL‐36α in minor salivary glands of pSS. γδ T cells were not significantly expanded in the salivary glands of pSS but produced more IL‐17, as their percentage correlated with the focus score. Higher expression of IL‐36α and IL‐36R was also demonstrated in γδ T cells isolated from pSS compared to controls. In this study we demonstrate that a significant increase in circulating and tissue levels of IL‐36α occurs in pSS patients.
Summary The aim of this study was to investigate the expression of the interleukin (IL)-36 axis in patients with primary Sjögren's syndrome (pSS). Blood and minor labial salivary glands (MSG) ...biopsies were obtained from 35 pSS and 20 non-Sjögren's syndrome patients (nSS) patients. Serum IL-36alpha was assayed by enzyme-linked immunosorbent assay (ELISA). IL-36alpha, IL-36R, IL-36RA, IL-38, IL-22, IL-17, IL-23p19 and expression in MSGs was assessed by reverse transcription-polymerase chain reaction (RT-PCR), and tissue IL-36alpha and IL-38 expression was also investigated by immunohistochemistry (IHC). alphabeta and gammadelta T cells and CD68+ cells isolated from MSGs were also studied by flow cytometry and confocal microscopy analysis. IL-36alpha was over-expressed significantly in the serum and in the salivary glands of pSS. Salivary gland IL-36alpha expression was correlated with the expression levels of IL-17, IL-22 and IL-23p19. IL-38, that acts as inhibitor of IL-36alpha, was also up-regulated in pSS. alphabeta+ CD3+ T cells and CD68+ cells were the major source of IL-36alpha in minor salivary glands of pSS. gammadelta T cells were not significantly expanded in the salivary glands of pSS but produced more IL-17, as their percentage correlated with the focus score. Higher expression of IL-36alpha and IL-36R was also demonstrated in gammadelta T cells isolated from pSS compared to controls. In this study we demonstrate that a significant increase in circulating and tissue levels of IL-36alpha occurs in pSS patients.
To review the evidence for the efficacy and safety of biological agents in patients with rheumatoid arthritis (RA) to provide data to develop treatment recommendations by the European League Against ...Rheumatism (EULAR) Task Force.
Medline, Embase and Cochrane databases were searched for relevant articles on infliximab (IFX), etanercept (ETN), adalimumab (ADA), certolizumab-pegol (CZP), golimumab (GLM), anakinra (ANA), abatacept (ABT), rituximab (RTX) and tocilizumab (TCZ) published between 1962 and February 2009; published abstracts from the 2007-2008 American College of Rheumatology (ACR) and EULAR conference were obtained.
87 articles and 40 abstracts were identified. In methotrexate (MTX) naïve patients, biological therapy with IFX, ETN, ADA, GLM or ABT has been shown to improve clinical outcomes (level of evidence 1B). In MTX/other synthetic disease-modifying antirheumatic drug (DMARD) failures all nine biological agents confer benefit (1B), with lower efficacy noted for ANA. RTX, ABT, TCZ and GLM demonstrate efficacy in tumour necrosis factor inhibitor (TNFi) failures (1B). Less evidence exists for switching between IFX, ETN and ADA (3B). Biological and MTX combination therapy is more efficacious than a biological agent alone (1B). A safety review shows no increased malignancy risk compared with conventional DMARDs (3B). TNFi are generally associated with an increased risk of serious bacterial infection, particularly within the first 6 months of treatment initiation; increased tuberculosis (TB) rates with TNFi are highest with the monoclonal antibodies (3B).
There is good evidence for the efficacy of biological agents in patients with RA. Safety data confirm an increased risk of bacterial infection and TB with TNFi compared with conventional DMARDs.
A consensus paper concerning the interaction of anti-rheumatic drugs and reproduction was published in 2006, representing data collected during the year 2004 and 2005. Because of an increasing use of ...biological agents in women of fertile age, the information was updated for the years 2006 and 2007. Experts disagree whether TNF-inhibitors should be stopped as soon as pregnancy is recognized or may be continued throughout pregnancy. Pregnancy experience with abatacept and rituximab is still too limited to prove their safety for the developing fetus. They must be withdrawn before a planned pregnancy. LEF has not been proven to be a human teratogen. Registries of transplant recipients have shown that cyclosporin (CsA) and tacrolimus do not increase the rate of congenital anomalies, whereas mycophenolate mofetil (MMF) clearly carries a risk for congenital anomalies. Prophylactic withdrawal of drugs before pregnancy is mandatory for abatacept, rituximab, LEF and MMF. Data remain insufficient for gonadal toxicity of immunosuppressive drugs in men and for excretion of these drugs in human breast milk.
Objectives. To assess the prevalence and severity of inflammatory abnormalities of the hand, wrist and foot joints in SLE patients by US and to correlate them with clinical, laboratory and disease ...activity score parameters.
Methods. Sixty-two consecutive SLE patients were enrolled in the present study and underwent clinical evaluation, laboratory tests and bilateral high-resolution US of the hand, wrist and foot joints. Joint effusion (JE), synovial hypertrophy (SH) and local pathological vascularization power Doppler (PD) were evaluated according to both a dichotomous score and a semi-quantitative (0–3) grading system. In addition, a global US score was calculated by summing the values given to each elementary lesion for every single joint and every joint group. US findings were correlated with physical examination, serological parameters (CRP, ANA, anti-dsDNA, ENA, aPL, C3 and C4 serum levels) and disease activity indexes (SLEDAI-2K, ECLAM).
Results. US detected inflammatory joint abnormalities in 54/62 patients (87.1%); 72.6% presented involvement of the MTP joints, 46.7% the MCP joints, 19.3% the PIP joints and 53% the wrists. A total of 1984 joints were examined highlighting JE in 19.1% of cases, SH in 6.9% and positive PD in 1.1%. The global US inflammatory score had a mean value of 10.9 (s.d. 15.2). No correlations were found between US findings and SLE disease activity parameters.
Conclusion. US demonstrated a high prevalence of inflammatory joint abnormalities in SLE that were also present in asymptomatic patients. Interestingly, the foot joints were the most frequently involved. US is a valuable tool for detecting subclinical synovitis in SLE.
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