An inception cohort of patients with systemic lupus erythematosus from 14 European centres was followed for up to 5 years in order to describe the current early disease course. At inclusion patients ...(n = 200, 89% female, mean age 35 years, 97% Caucasian, mean SLEDAI 12.2) fulfilled a mean of 6.5 ACR classification criteria. The most prevalent criteria were antinuclear Ab presence (97%) followed by anti-dsDNA Ab (74%), arthritis (69%), leukocytopenia (54%) and malar rash (53%), antiphospholipid Ab (48%) and anti-synovial membrane Ab (21.6%). Clinical signs of lupus nephritis (LN) were present in 39% with biopsy-confirmed LN seen in 25%. Frequent additional findings were hypocomplementaemia (54%), anti-SSA Ab (49%), alopecia (26%) and Raynaud’s phenomenon (31%). There were few regional differences in disease presentation and management. One and 5-year survival rates were 99% and 97% respectively. During the mean follow-up of 4.1 years 25% entered a state of early disease quiescence by global physician assessment, but the overall risk of subsequent flare was 60%. Maximum SLEDAI scores decreased over time, but 45% of patients accrued damage (SDI ≥1) for which baseline presence of proteinuria and persistent disease activity were independent predictors. The results indicate minor differences in SLE presentation and treatment within various regions of Europe and a high diagnostic reliance on anti-dsDNA Ab. Despite early reductions in disease activity and improved mortality, the risk for disease flare and damage development is, however, still substantial, especially in patients not entering an early remission.
Current therapeutic and diagnostic resources have turned systemic lupus erythematosus (SLE) into a chronic disease by reducing mortality rates. The exact contribution of disease activity and disease ...related damage to mortality is not well studied. The aim of this study was to describe the current causes of death (COD) in a multinational European cohort of patients with SLE in relation to quantified measures of disease activity and damage. Prospective five-year observational study of case fatalities in SLE patients at 12 European centres was performed. Demographics, disease manifestations, interventions and quantified disease activity (by ECLAM and SLEDAI) and damage (by SLICC-DI) at the time of death were related to the various COD. Ninety-one case fatalities (89% females) occurred after median disease duration of 10.2 years (range 0.2—40) corresponding to a annual case fatality of one for each of the participating cohorts. Cumulative mortality correlated linearly with disease duration with nearly 10% of fatalities occurring in the first year and 40% after more than 10 years of disease. Death occurred during SLE remission in one third of cases. In the remaining cases a mixture of disease activity (median ECLAM 5.5, median SLEDAI 15) and accrued damage (median SLICC-DI 5.0) with opposing relationships to disease duration contributed to death. Infections and cardiovascular events were the most frequent COD in both early and late fatalities with no gender differences for type of COD, disease activity, damage or comorbidity. In Europe, case fatalities have become uncommon events in dedicated SLE cohorts. The bimodal mortality curve has flattened out and deaths now occur evenly throughout the disease course with infectious and cardiovascular complications as the main direct COD in both early and late fatalities. Accrued damage supplants disease activity over time as the main SLE specific contributor to death over time. Lupus (2007) 16, 309—317.
OBJECTIVE To develop criteria for disease activity in systemic sclerosis (SSc) that are valid, reliable, and easy to use. METHODS Investigators from 19 European centres completed a standardised ...clinical chart for a consecutive number of patients with SSc. Three protocol management members blindly evaluated each chart and assigned a disease activity score on a semiquantitative scale of 0–10. Two of them, in addition, gave a blinded, qualitative evaluation of disease activity (“inactive to moderately active” or “active to very active” disease). Both these evaluations were found to be reliable. A final disease activity score and qualitative evaluation of disease activity were arrived at by consensus for each patient; the former represented the gold standard for subsequent analyses. The correlations between individual items in the chart and this gold standard were then analysed. RESULTS A total of 290 patients with SSc (117 with diffuse SSc (dSSc) and 173 with limited SSc (lSSc)) were enrolled in the study. The items (including Δ-factors—that is, worsening according to the patient report) that were found to correlate with the gold standard on multiple regression were used to construct three separate 10-point indices of disease activity: (a) Δ-cardiopulmonary (4.0), Δ-skin (3.0), Δ-vascular (2.0), and Δ-articular/muscular (1.0) for patients with dSSc; (b) Δ-skin (2.5), erythrocyte sedimentation rate (ESR) >30 mm/1st h (2.5), Δ-cardiopulmonary (1.5), Δ-vascular (1.0), arthritis (1.0), hypocomplementaemia (1.0), and scleredema (0.5) for lSSc; (c) Δ-cardiopulmonary (2.0), Δ-skin (2.0), ESR >30 mm/1st h (1.5), total skin score >20 (1.0), hypocomplementaemia (1.0), scleredema (0.5), digital necrosis (0.5), Δ-vascular (0.5), arthritis (0.5), Tlco <80% (0.5) for all patients with SSc. The three indexes were validated by the jackknife technique. Finally, receiver operating characteristic curves were constructed in order to define the value of the index with the best discriminant capacity for “active to very active” patients. CONCLUSIONS Three feasible, reliable, and valid preliminary indices to define disease activity in SSc were constructed.
Objectives To estimate the correlation between osteoporosis and vascular calcification in postmenopausal women and the influence of calcium/vitamin D supplements on vascular calcification. Methods A ...cross-sectional study was performed including 29 women with osteoporosis (15 not taking supplements) and 18 age-matched, non-osteoporotic women. They were evaluated for cardiovascular risk factors and blood tests, lateral X-ray of lumbar spine (assessment of abdominal aorta calcification, AAC) and carotid ultrasound (increased intima media thickness (iIMT) or calcified plaques) were performed. Results In univariate analysis, osteoporotic women were 16 times more likely to develop AAC (odds ratio (OR) 15.8, 95% confidence interval (CI) 1.9-135.4) and seven times more likely to develop iIMT (OR 6.8, 95% CI 1.8-25.4) compared to normal individuals. The odds of developing AAC and iIMT were increased each year after menopause (OR 1.11, 95% CI 1.01-1.2 and OR 1.18, 95% CI 1.05-1.3, respectively) and with aging (OR 1.27, 95% CI 1.1-1.47 and OR = 1.17, 95% CI 1.04-1.3, respectively). Calcified plaques were significantly correlated with osteoporosis (p = 0.014). In multivariate analysis, osteoporosis was an independent risk factor for AAC (OR 13.3, 95% CI 1.3-134.4) and iIMT (OR 4.7, 95% CI 1.1-19.9). Low doses of supplements did not appear to affect vascular calcification (p = 0.6). Conclusions Osteoporosis is associated with increased calcification of the abdominal aorta and carotids. Low doses of supplements do not appear to cause any increase in vascular calcification in osteoporotic women.
Background Platelet derived chemokines, such as PF-4 and a recently isolated protein product of its nonallelic variant gene PF-4var, are implicated in several aspects of vascular thrombosis and ...inflammation. The above chemokines present only 4.3% aminoacid divergence in the mature proteins; however they exhibit distinct platelet secretion mode and function. The precise role of PF-4var regarding the haemostatic balance is not yet studied. Previous study from our group demonstrates a novel interaction between β2-glycoprotein I (β2GPI), the major autoantigen in APS, and PF-4 or PF-4var. This complex formation leads in the stabilization of β2GPI dimeric structure which facilitates the antibody recognition and platelet activation, as indicated by p38MAPK phosphorylation and thromboxane production. Objectives To determine PF-4var plasma levels in patients with APS and evaluate the correlation with clinical and laboratory parameters of the disease. Methods From 70 patients, who fulfill the revised diagnostic criteria for APS, blood samples were taken and separate samples of serum, plasma and platelets were isolated. Complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), aPTT, anti-cardiolipin (anti-CL) and anti-β2GPI antibodies were measured. A healthy control (n=20) and a disease control group (SLE, n=10) were included in the study (study in progress to increase the number of both groups). Plasma levels of PF-4var were determined using a commercially available ELISA, which absolutely discriminates PF-4var from PF-4 protein. Statistical analyses were evaluated by Mann-Whitney t-test and Kruskal-Wallis test. Results APS patients showed higher levels of PF-4var compared to healthy individuals (median 137 pg/ml; intarquartile range 66.4-200.5 pg/ml versus 79.03 40.3-99.2 pg/ml, p=0.0052). PF-4var levels were significantly elevated in patients suffering from primary APS (PAPS) than those with APS secondary to SLE (SAPS), (197.7 113.3-304.8 pg/ml versus 126.6 49.94-170 pg/ml, p=0.0086). Regarding the clinical presentation of the disease, patients who experienced thrombotic events versus pregnancy morbidity or arterial versus venous thrombotic events do not show statistically significant difference in PF-4var levels. A positive correlation was also revealed between the presence of thrombocytopenia and the elongation of aPTT with the higher PF-4var levels (p= 0.0048 and p=0.0195, respectively). Conclusions Preliminary results suggest that higher PF-4var levels are present in plasma of APS patients and especially in those with PAPS and these are associated with laboratory characteristics indicative for higher risk of thrombotic complications. Disclosure of Interest: None Declared
BackgroundA number of cross-sectional studies have shown that approximately one quarter of rheumatoid arthritis (RA) patients are being treated with biologic disease modifying anti-rheumatic drugs ...(bDMARDs) as monotherapy. Data regarding the retention of bDMARD monotherapy in real-life settings are limited.ObjectivesTo study the survival rate of bDMARD monotherapy in RA patients in daily clinical practice.MethodsMulticenter (11 hospital, 3 private office practices), prospective, RA epidemiological study in Greece. At baseline and after one year of follow-up, demographics, disease characteristics, treatments, co-morbidities and serious events (serious infections, cardiovascular events, neoplasms, osteoporotic fractures) were collected via a web-based platform.Results1.323 RA patients with paired evaluations one year apart (mean interval: 13.2±3.7 months) were included. Among 611 bDMARD treated patients, 155 patients (25%) were on bDMARD monotherapy (women: 87%, mean age: 60.4 years, mean disease duration: 15 years, RF and/or anti-CCP positive: 66%, TNFi therapy: 57%). The majority had been previously on and had discontinued their csDMARDs (90%). During follow-up, 15% (n=24) discontinued their bDMARD; most of them stayed off any type of therapy (83%) while the rest continued with synthetic DMARD (csDMARD) monotherapy (17%). From the remaining 131 patients, 96 (73%) remained on bDMARD monotherapy (85%, n=82 on the same biologic) while in 27% (n=35) a csDMARD was added. Serious events occurred in 7.7% of patients (n=12). Overall, at the end of 1st year, approximately half of patients (53%, n=82) remained on their initial bDMARD monotherapy. Factors associated with continuation of the same bDMARD by multivariate analysis were a low HAQ score (OR=0.48, 95% C.I.=0.23–0.99, p=0.047) and corticosteroid use (OR=2.2, 95% C.I.=1.02–5.1, p=0.044) at baseline as well as the absence of a serious event during the 1st year of follow-up (OR=0.14, 95% C.I.=0.016–1.3, p=0.094).ConclusionsIn real life settings, only half of patients who are on bDMARD monotherapy continue the same agent one year later. Low HAQ score, corticosteroid use and absence of a serious event during therapy predicted bDMARD monotherapy survival.AcknowledgementsSupported by grants from the Greek Rheumatology Society and Professional Association of Rheumatologists.Disclosure of InterestNone declared
BackgroundIt is unclear if the widespread use of biologic DMARDs (bDMARDs) and the implementation of the treat to target approach have led to better disease control in patients with rheumatoid ...arthritis (RA) in daily clinical practice.ObjectivesTo study the longitudinal changes in disease activity in a large, real life, longitudinal RA cohort.MethodsMulticenter (11 hospitals, 3 private offices), prospective, RA epidemiological study in Greece. Demographics, disease characteristics, treatments and co-morbidities were collected via a web-based platform in registered patients at baseline and one year after their 1st visit.Results1.096 RA patients with available paired evaluations one year apart (mean interval: 13.4±3.6 months) were included (women: 78%, mean age: 62.8 years, mean disease duration: 11 years, RF and/or anti-CCP positive: 60%, mean HAQ: 0.44±0.56). At baseline, 50% (n=548) of patients were on conventional DMARDs (csDMARDs) alone, 35% on cs- and b-DMARD combination (n=379) and 11% on bDMARD monotherapy (n=124). Among bDMARD treated patients, 60% were receiving tumour necrosis factor inhibitors (TNFi) while 40% were on corticosteroids (mean daily dose: 4.7 mg). Despite these therapies, 43% of patients had active disease (DAS28-ERS>3.2); 34% moderate (MDA, DAS28-ESR=3.2–5.1) and 9% high (HDA, DAS28-ESR>5.1) disease activity. During the 1 year observation period, among the group of patients with MDA who were only on csDMARDs, 15% started a bDMARD while among those on bDMARDs, 11% switched to another bDMARD. The respective rates of starting a bDMARD (in those on csDMARDs) or switching to another bDMARD (in those on bDMARDs), were much higher for patients in the HDA group (41% and 32% respectively, p<0.001 for both groups). At the end of the 1st year, the proportion of patients on TNFi and corticosteroids was 57% and 32%, respectively. Overall, despite a decrease in the DAS28-ESR score (from 3.2±1.2 to 2.9±1.3, p<0.001), 37% of patients had still active disease (6% improvement after 1 year; MDA: 30%, HDA: 7%).ConclusionsIn a large, real life, RA cohort with almost half of patients on bDMARD-based therapies, more than one third of patients had still active disease at the end of the 1st year of follow-up. These findings could be explained in part by the low rate of bDMARD initiation or switching in this cohort or they could indicate the limitations of current therapeutic approaches in RA patients with longstanding disease in Greece.AcknowledgementsSupported by grants from the Greek Rheumatology Society and Professional Association of Rheumatologists.Disclosure of InterestNone declared
Objective: To further assess the construct validity of the three European Scleroderma Study Group (EScSG) preliminary activity indices for systemic sclerosis (SSc): for SSc as a whole, for diffuse ...SSc (dcSSc), and for limited SSc (lcSSc). Methods: 30/290 SSc clinical charts collected for the EScSG study used to develop activity criteria for SSc were selected and sent to four clinical experts in SSc. The experts ranked the charts from 1 to 30 (1=lowest activity, 30=highest activity). The relationships among the ranks given by each investigator and each of the three scores, and between any two of the ranks were investigated. Results: A consistently significant correlation (rs=0.530–0.712) was found between the ranks given by each of the four investigators and the index for the entire patient group. A similar level of agreement was detected between each couple of the four experts (rs=0.428–0.720). Moreover, the ranks given in patients with an index >3 were significantly higher than those given for patients with an index ⩽3. This cut off point had previously been shown to best discriminate patients with active disease. Conclusions: Of the originally developed activity indexes, the whole series index has been externally validated. The index comprises the first preliminary, but necessary, groundwork to improve the concept of disease activity in SSc, which is still ill defined. It can be used as a preliminary activity index in clinical investigational studies.
Objective. To evaluate whether premenopausal women with antiphospholipid syndrome (APS) or systemic lupus erythematosus (SLE) have increased prevalence of atherosclerosis after adjustment has been ...made for known cardiovascular risk factors. Methods. We evaluated premenopausal women with APS in comparison with age‐matched groups of patients with SLE positive or negative for anticardiolipin (aCL) antibodies or rheumatoid arthritis (RA), and healthy subjects. Thirty‐three subjects in each group were assessed for cardiovascular risk factors, including a detailed lipid profile. Ultrasonography of carotid and femoral arteries assessed the intima‐media thickness (IMT) and the presence of atherosclerotic plaque. Results. Atherosclerotic plaques were detected in 5, 2, 4, 1 and 1 subject in the five groups respectively. APS patients had significantly more affected vessels than RA patients and healthy controls (P=0.042 and P=0.016, respectively), but not compared with SLE patients. No consistent differences in IMT, traditional cardiovascular risk factors or lipid parameters were detected among the five groups. The odds for atherosclerosis independently increased 1.19‐fold per year of increasing age 95% confidence interval (CI) 1.08–1.31; P=0.001), 1.019‐fold per 1 mg/dl increase in low‐density lipoprotein (LDL) (95% CI 1.003–1.036; P=0.020), 1.035‐fold per additional 1 g of methylprednisolone equivalent cumulative corticosteroid dose (95% CI, 0.996–1.074; P=0.074), and 4.35‐fold in the presence of APS or SLE (95% CI 0.75–25.2; P=0.10). Neither aCL nor anti‐β2GPI antibodies were associated with atherosclerosis. Conclusion. Premenopausal APS and SLE women have an increased prevalence of carotid and femoral plaque that is not accounted for by other predictors of atherosclerosis, including age, lipid parameters and cumulative steroid dose.
Objective: To evaluate the prevalence of antinuclear antibodies (ANA) in patients with autoimmune thyroid diseases (ATD) and the presence of systemic autoimmune disorders among ANA positive patients ...with ATD. Methods: 168 consecutive patients with ATD with positive antithyroid antibodies and 75 healthy subjects were tested for the presence of ANA. ANA positive patients were further evaluated by complete history, physical examination, blood and urine tests, and immunological studies. Patients with subjective xerophthalmia and xerostomia were examined by objective tests. Results: 58/168 (35%) patients with ATD were ANA positive compared with 7/75 (9%) healthy controls (p = 0.001). Of 58 ANA positive patients, 6 (10%) had anti-Ro antibodies, 1 had anti-Ro and anti-La antibodies, 7 (12%) had anti-dsDNA antibodies, and 7 (12%) had medium levels of IgG and/or IgM anticardiolipin antibodies (aCL). No healthy subjects had positive anti-dsDNA, antibodies against the extractable nuclear antigens, or aCL. 5/58 (9%) patients fulfilled the criteria for Sjögren’s syndrome (SS). Two patients had features related to systemic lupus erythematosus. No healthy subjects had clinical or laboratory characteristics of systemic autoimmune disorders. Conclusion: ANA are detected in 1/3 of patients with ATD. Anti-dsDNA, anti-Ro, and aCL can also be found in ANA positive patients with ATD. SS occurs in about 1/10 of ANA positive patients with ATD.
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