High Degree Of Disease Activity Research Articles

#1852 When ‘pebbles’ affect the kidney: nephrolithiasis and chronic renal failure in Crohn's disease. The experience of a 3rd level centre

Abstract Background and Aims Nephrolithiasis is the most common expression of kidney involvement in chronic inflammatory bowel disease (IBD), especially in Crohn's disease (CD). Stone formation favoring factors are hyperoxaluria, dehydration, acidosis, common conditions in CD patient, who present a little higher incidence of renal stones, made of calcium oxalate, than the normal population. Only few studies focused on the relationship between CD activity (defined by CDAI score) and the development of nephrolithiasis and possible subsequent development of chronic renal failure (CRF). Materials and Method We conducted a retrospective study on a cohort of 1236 patients affected by CD referring to our Centre of IBD- Sant'Orsola between 2014 and 2021. We identified two cohorts from this population: 118 patients with nephrolithiasis and 118 patients without nephrolithiasis. Among these two groups, we identified variable clinical manifestations of CD and their relation with CRF and lithiasis. Results The prevalence of nephrolithiasis in all CD patients was 10.3%, a little higher than in the general population. The results of the analysis of patient and disease variables in the two groups are shown in Table 1. The mean age at diagnosis of CD was higher in the group without nephrolithiasis, so the treatment was started later. The presence of perianal disease, extraintestinal manifestations (MEI), like ankylosing spondylitis (APS), biliary tract involvement, or previous surgery, and presence of ileostomy correlate with the formation of stones in univariate regression analysis (Table 2). Perianal disease and MEI also maintained significance in multivariate analysis. Conclusion Our data suggest that a higher degree of disease activity, defined by the presence of perianal disease (a variable on CDAI score) and the presence of MEI, correlates with higher risk of lithiasis. It is advisable to start early the study of nephrolithiasis in these patients to adopt preventive strategies against formation and progression of renal stones. Future studies are required for a better definition of this deep relationship.

BCD020 rituximab bioanalog compared to standard treatment in juvenile systemic lupus erythematosus: The data of 12 months case-control study.

Systemic lupus erythematosus (SLE) is the most frequent and serious systemic connective tissue disease. Nowadays there is no clear guidance on its treatment in childhood. There are a lot of negative effects of standard-of-care treatment (SOCT), including steroid toxicity. Rituximab (RTX) is the biological B-lymphocyte-depleting agent suggested as a basic therapy in pediatric SLE. To compare the benefits of RTX above SOCT. The data from case histories of 79 children from the Saint-Petersburg State Pediatric Medical University from 2012 to 2022 years, were analyzed. The diagnosis of SLE was established with SLICC criteria. We compared the outcomes of treatment of SLE in children treated with and without RTX. Laboratory data, doses of glucocorticosteroids, disease activity measured with SELENA-SLEDAI, and organ damage were assessed at the time of initiation of therapy and one year later. Patients, treated with RTX initially had a higher degree of disease activity with prevalence of central nervous system and kidney involvement, compared to patients with SOCT. One year later the disease characteristics became similar between groups with a more marked reduction of disease activity (SELENA-SLEDAI activity index) in the children who received RTX [-19 points (17; 23) since baseline] compared to children with SOCT [-10 (5; 15.5) points since baseline, P = 0.001], the number of patients with active lupus nephritis, and daily proteinuria. During RTX therapy, infectious diseases had three patients; one patient developed a bi-cytopenia. RTX can be considered as the option in the treatment of severe forms of SLE, due to its ability to arrest disease activity compared to SOCT.

Clinical efficacy of a method for identifying patients at high risk of carotid atherosclerosis in rheumatoid arthritis

Objective: to test the patented “Method for determining a high risk of atherosclerosis in rheumatoid arthritis” on patients with rheumatoid arthritis.Materials and methods: 74 patients with RA who underwent inpatient treatment were examined. Gender composition of respondents: 77% women and 23% men. Mean age 54.1±9.1 years. The duration of RA is from 1 year to 26 years. 85.1% were diagnosed with a high degree of disease activity. Erosive arthritis was detected radiographically in 41 patients (55.4%). 83.7% (n=62) were seropositive for RF, 81% for ACCP (n=60). All received basic anti-inflammatory therapy. Systemic glucocorticoid therapy was received by 33.7%. All patients were calculated cardiovascular risk according to SCORЕ and mSCORЕ Also, all patients underwent duplex scanning of the BCA to detect atherosclerosis.Results: no significant increase in traditional factors of cardiovascular diseases was found among patients. When CVR was stratified according to SCORE, the frequency of low risk was 32.4%, moderate — 59.5%, high — 5.4%, very high — 2.7%. When using mSCORE, low risk was found in 27%, moderate — 56.7%, high — 13.5%, very high — 2.7%. Atherosclerotic plaques (ASP) in the carotid arteries in patients stratified according to SCORE for moderate, high and very high risk was detected in 68%, in persons with similar risks according to mSCORE — in 66.7%. With a score of 4 or more when using the tested method, ASP was found in 77.8%. Sensitivity for the detection of ASP in the carotid arteries using SCORE was 0.77, with mSCORE and the tested method 0.81 and 0.95, respectively. Specificity 0.47, 0.4 and 0.6 respectively. Positive predictive power for SCORE — 0.68, mSCORE — 0.67, tested method — 0.77. Negative predictive power for SCORE — 0.58, mSCORE — 0.6, tested method — 0.9.Conclusion: the study showed that our proposed method, which uses traditional clinical markers, significantly increases the sensitivity, specificity, and negative predictive power of calculation methods for identifying a group of individuals with a high risk of atherosclerotic lesions of extracranial arteries against the background of rheumatoid arthritis compared with using the SCORE and mSCORE parameters.

Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial

BackgroundBelimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate.MethodsSynbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections.DiscussionThe Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE.Trial registrationClinicalTrials.gov NCT03747159. Registered on 20 November 2018.

Plasma extracellular DNA and neutrophilic leukocyte activity in patients with rheumatoid arthritis

Neutrophilic leukocytes play a key role for the joint damage in development of rheumatoid arthritis (RA). The specific death mode of these cells (netosis) may be an important reason of increase of cell-free DNA (cfDNA) in peripheral blood of the RA patients. Of great interest would be studies of alleged relationships between the of blood cfDNA contents being able of playing the role of an auto-antigen participating in the initiation of autoimmune reactions, and indices of neutrophil activation in this immunopathological disorder. The aim of the present study was to determine the levels of cfDNA in blood plasma of patients with RA depending on the clinical course of the disease, and to evaluate possible relationships between this index and activation of neutrophilic leukocytes. The study was conducted on 28 conditionally healthy donors and 63 patients with RA from the Rheumatology Department at the Clinic of Immunopathology (Novosibirsk). The level of cfDNA was determined using PicoGreen fluorescent dye. Neutrophils from the peripheral blood of donors and patients with rheumatoid arthritis were isolated in a Ficoll-Urografin density gradient. Neutrophilic leukocytes accounted for more than 98% of the fraction of isolated cells, and their viability was 99%. A portion of freshly isolated neutrophils was stimulated by phorbol myristate acetate. Concentration of myeloperoxidase in blood plasma of donors and patients with RA was determined using the Human MPO ELISA kit. It has been shown that the increased concentration of extracellular DNA in blood plasma of RA patients correlates with an higher degree of disease activity, and this parameter may serve as a relatively independent indicator of the disease intensity. A correlation was found between the level of cfDNA and common biochemical markers used to assess the activity of disease, i.e., DAS-28 and C-reactive protein levels in serum (p 0.05). Decrease of cfDNA concentrations is detected during treatment of the RA patients. This is due to the expected prognosis, i.e., a decreased manifestation of the disease, which also means correct administration of therapy. A relationship was found between the level of cfDNA and blood myeloperoxidase concentration in RA patients. The data obtained during the study suggest a possible connection between increased concentration of extracellular DNA, and activation of neutrophilic leukocytes in rheumatoid arthritis, with increased netosis in the affected joints.

Clinical-pathogenetic significance of middle mass molecules of different fractions in pulmonary expirates of patients with rheumatoid arthritis

Objective — to establish the clinical and pathogenetic role of the isolation of the middle mass molecules of different fractions (aminopeptide — AF, peptide — PF, nucleotide — NF, chromatophore — CF) in exhaled breath concentrate (EBC) in pneumonitis in rheumatoid arthritis (RA) patients, their relationship with the parameters of respiratory moisture excretion, spirography and pressure in the pulmonary artery. 
 Materials and methods. EBC (pulmonary expirates) were studied in 31 patients with RA (mean age 46 years, the ratio of men to women 1 : 2), among whom moderate and high degree of disease activity was established in 67.7 % of cases, III and IV stages — in 54.8 %, the extra­articular form of the disease — in 61.3 %, systemic osteoporosis — in 83.9 %, seropositivity for rheumatoid factor — in 80.7 %, for antibodies to cyclic citrullined peptide — in 77.4 %. To determine the middle mass molecules in the expirates and blood serum, a screening method was used with the precipitation of proteins with trichloroacetic acid and the determination of the light absorption spectra of the acid­soluble fraction. 
 Results and discussion. Interstitial pneumonitis was diagnosed in 51.6 % of the number of RA patients, which was accompanied by fibrosing alveolitis in 18.8 % of cases, rheumatoid nodules in the lungs — in 12.5 %, obliterating bronchiolitis — in 6.3 %, with the ratio of restrictive, mixed and obstructive types of dysfunctions of external respiration 6 : 2 : 1, while the disease proceeded with a significant increase in AF indicators in 74.2 % of patients and the ratio «EBC/blood» (e/b) PF level in 77.4 % against the background of a decrease in AFe/b (at 71.0 %), NFe/b (at 54.8 %, CFe/b (at 74.2 %) and the ratio of surface tension caused by high­ and low­molecular substances in 83.9 %, and the composition of expirates was closely interrelated with the state of hemodynamics of the pulmonary circulation and bronchopermeability, depended on the rate and volume of respiratory moisture release, long­term use in the complex treatment of patients with an immunosuppressant of cytotoxic action, folic acid antagonist methotrexate. Conclusions. The nature of the respiratory excretion of middle mass molecules of different fractions determines the pathogenesis of pneumopathy in RA patients, which depends on the clinical, radiological and sonographic signs of the disease, and the study of EBC can be used to predict the course of the pathological process and monitor the effectiveness of therapeutic measures.

Gender differences in patient journey to diagnosis and disease outcomes: results from the European Map of Axial Spondyloarthritis (EMAS)

Introduction/objectivesTo evaluate the journey to diagnosis, disease characteristics and burden of disease in male and female patients with axial spondyloarthritis (axSpA) across Europe.MethodData from 2846 unselected patients participating in the European Map of Axial Spondyloarthritis (EMAS) study through an online survey (2017–2018) across 13 countries were analysed. Sociodemographic characteristics, lifestyle, diagnosis, disease characteristics and patient-reported outcomes (PROs) [disease activity –BASDAI (0–10), spinal stiffness (3–12), functional limitations (0–54) and psychological distress (GHQ-12)] were compared between males and females using chi-square (for categorical variables) and student t (for continuous variables) tests.ResultsIn total, 1100 (38.7%) males and 1746 (61.3%) females participated in the EMAS. Compared with males, females reported considerable longer diagnostic delay (6.1 ± 7.4 vs 8.2 ± 8.9 years; p < 0.001), higher number of visits to physiotherapists (34.5% vs 49.5%; p < 0.001) and to osteopaths (13.3% vs 24.4%; p < 0.001) before being diagnosed and lower frequency of HLA-B27 carriership (80.2% vs 66.7%; p < 0.001). In addition, females reported higher degree of disease activity in all BASDAI aspects and greater psychological distress through GHQ-12 (4.4 ± 4.2 vs 5.3 ± 4.1; p < 0.001), as well as a greater use of alternative therapies.ConclusionThe patient journey to diagnosis of axSpA is much longer and arduous in females, which may be related to physician bias and lower frequency of HLA-B27 carriership. Regarding PROs, females experience higher disease activity and poorer psychological health compared with males. These results reflect specific unmet needs in females with axSpA needing particular attention.Key Points• Healthcare professionals’ perception of axSpA as a predominantly male disease may introduce some bias during the diagnosis and management of the disease. However, evidence about male-female differences in axSpA is scarce.• EMAS results highlight how female axSpA patients report longer diagnostic delay and higher burden of the disease in a large sample of 2846 participants of 13 European countries.• Results reflect unmet needs of European female patients. Healthcare professionals should pay close attention in order to accurately diagnose and efficiently manage axSpA cases while further research should be developed on the cause of reported gender differences.

Long-Term Consequences of High Titer Neutralizing Antibodies to Interferon-β in Multiple Sclerosis.

BackgroundNeutralizing anti-drug antibodies (NAbs) to interferon beta (IFNβ) develop in up to 47% of multiple sclerosis (MS) treated patients inhibiting treatment effect of IFNβ. However, the long-term effect of NAbs remain unknown.ObjectiveTo investigate the long-term consequences of high titer NAbs to IFNβ on disease activity and progression in MS patients.MethodsAn observational study including data from all IFNβ treated relapsing remitting MS patients with sufficient NAb test results from the Swedish MS registry. Patients were classified into either confirmed ‘high titer’ or ‘persistent negative’ groups and analyzed for differences in disease activity and progression over time.ResultsA total of 197 high-titer and 2907 persistent negative patients with 19969.6 follow up years of data were included. High titer NAbs were associated with a higher degree of disease activity at baseline. However, even when accounting for this, the presence of high titer NAbs were also associated with higher disease activity during IFNβ treatment. This persisted even after the next DMT start, suggesting that earlier high titers may partially reduce the effect of later treatments. No difference was found in confirmed disability progression.ConclusionHigh titer NAbs to IFNβ are associated with higher disease activity, persisting even after IFNβ discontinuation or switch. These results support use of highly efficient treatment earlier in patients with active disease, to avoid these complications.

High interleukin-18 and low FOXP3 mRNAs in peripheral blood of women with severe systemic lupus erythematosus: a cross-sectional study.

Gene expression analysis of peripheral blood cells may provide valuable information about the triggered molecular processes in systemic lupus erythematosus (SLE). The study aimed to quantify the mRNA in peripheral blood of seven target genes, including inflammatory cytokine genes (IL23A, IL12B, TNFA, IL18), and T regulatory-related genes (FOXP3, TGFB1, IL10) in patients with SLE and to correlate expression levels with disease activity and/or clinical manifestations. The relative quantification of target genes was performed using real-time polymerase chain reaction in peripheral blood obtained from 28 adult SLE females and 17 healthy women. The highest up-regulation in the blood of SLE patients was observed for IL23A with a median 9.54 (p < 0.0001), followed by TGFB1 (median: 2.07; p = 0.047) and IL10 (median: 1.84; p = 0.013). IL12B and TNFA were significantly down-regulated in patients compared to controls (median: 0.521; p = 0.0023, and median: 0.519; p = 0.0003, respectively). FOXP3 mRNA was lower among patients with higher degree of disease activity (median: 0.338; p = 0.029) and showed inverse correlation with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). IL18 mRNA correlated positively with the SLEDAI and was highly expressed during severe flares (median: 1.216; p = 0.021). IL18 up-regulation was associated with anti-dsDNA antibody positivity, while FOXP3 down-regulation with lupus nephritis. Our study pointed out the relationship of SLE disease activity and particular clinical manifestations with IL18 and FOXP3 expression, and the significant contribution of IL23A in the SLE immunopathogenesis. Hence, the peripheral blood cytokine mRNAs should be exploited as novel prognostic and diagnostic biomarkers.

Clinical characteristics and frequency of TLR4 polymorphisms in Brazilian patients with ankylosing spondylitis

ObjectivesInnate immunity is involved in the physiopathology of ankylosing spondylitis (AS), with the participation of Gram-negative bacteria, modulation of human leukocyte antigen (HLA) B27 and the involvement of pattern recognition receptors, such as Toll-like receptors (TLRs). The aim of this study was to investigate the clinical characteristics and frequency of TLR4 polymorphisms (Asp299Gly and Thr 399Ile) in a cohort of Brazilian patients with AS. MethodsA cross-sectional study was carried out involving 200 patients with a diagnosis of AS and a healthy control group of 200 individuals. Disease activity, severity and functional capacity were measured. The study of TLR4 polymorphisms was performed using the restriction fragment length polymorphism method. HLA-B27 was analyzed by conventional polymerase chain reaction. The IBM SPSS Statistics 20 program was used for the statistical analysis, with p-values less than 0.05 considered significant. ResultsMean age and disease duration were 43.1±12.7 and 16.6±9.2 years, respectively. The sample was predominantly male (71%) and non-Caucasian (52%). A total of 66% of the group of patients were positive for HLA-B27. The sample of patients was characterized by moderate functional impairment and a high degree of disease activity. No significant association was found between the two TLR4 polymorphisms and susceptibility to AS. ConclusionsTLR4 polymorphisms 399 and 299 were not more frequent in patients with AS in comparison to the health controls and none of the clinical variables were associated with these polymorphisms.

Características clínicas e frequência de polimorfismos em TLR4 em pacientes brasileiros com espondilite anquilosante

ObjectivesInnate immunity is involved in the physiopathology of ankylosing spondylitis (AS), with the participation of Gram‐negative bacteria, modulation of human leukocyte antigen (HLA) B27 and the involvement of pattern recognition receptors, such as Toll‐like receptors (TLRs). The aim of this study was to investigate the clinical characteristics and frequency of TLR4 polymorphisms (Asp299Gly and Thr 399Ile) in a cohort of Brazilian patients with AS. MethodsA cross‐sectional study was carried out involving 200 patients with a diagnosis of AS and a healthy control group of 200 individuals. Disease activity, severity and functional capacity were measured. The study of TLR4 polymorphisms was performed using the restriction fragment length polymorphism method. HLA‐B27 was analyzed by conventional polymerase chain reaction. The IBM SPSS Statistics 20 program was used for the statistical analysis, with p‐values less than 0.05 considered significant. ResultsMean age and disease duration were 43.1±12.7 and 16.6±9.2 years, respectively. The sample was predominantly male (71%) and non‐Caucasian (52%). A total of 66% of the group of patients were positive for HLA‐B27. The sample of patients was characterized by moderate functional impairment and a high degree of disease activity. No significant association was found between the two TLR4 polymorphisms and susceptibility to AS. ConclusionsTLR4 polymorphisms 399 and 299 were not more frequent in patients with AS in comparison to the health controls and none of the clinical variables were associated with these polymorphisms.

Correlation study between complement C3 level and degree of disease activity in patients with systemic lupus erythematosus

Objective To investigate the relationship between complement C3 level and the degree of disease activity in patients with systemic lupus erythematosus(SLE). Methods A total of 1 012 patients with SLE were enrolled in this study from January 2006 to December 2013 at department of rheumatology and immunology, the first affiliated hospital of Anhui medical university. Serum complement C3 level was detected by rate erythenephelometry assay. The relationship between reduction of complement C3 and SLE was analyzed. Results Serum complement C3 clearly decreased in 782 patients, accounted for 77.27%. There were significant differences concerning serum complement C3 level among different groups of disease activity (F=131.275, P<0.01). The low serum complement C3 level was correlated with the high degree of disease activity (r=-0.517, P<0.01). Patients with SLE had a severe disease activity (SLE disease activity index ≥15) when the level of serum complement C3 was less than 0.57 g/L. Serum complement C3 levels were positively correlated with serum complement C4 (r=0.845, P<0.01), peripheral blood leukocyte count (r=0.115, P<0.01), hemoglobin (r=0.069, P<0.01), platelet count (r=0.177, P<0.01) and albumin level (r=0.091, P<0.01). There was also a negative association of serum complement C3 with 24 h urinary protein (r=-0.228, P<0.01). 101 patients whose average level of serum complement C3 was(0.48±0.26)g/L, were treated with glucocorticoid pulse therapy as high degree of disease activity. Conclusions There is a close relationship between serum complement C3 level and the degree of disease activity in SLE. Serum complement C3 less than 0.57 g/L might be seen in SLE with severe disease activity. Key words: Lupus erythematosus, systemic; Complement system proteins; Disease activity

FRI0126 The Ankylosing Spondylitis Disease Activity Score (ASDAS): Defining the Best Calculation Method When the Conventional C-Reactive Protein (CRP) is below the Threshold of Detection - Results from the DESIR Cohort

BackgroundThe Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new Assessment of SpondyloArthritis international Society (ASAS) and Outcomes in Rheumatology (OMERACT)-endorsed measure of disease activity in axial spondyloarthritis (SpA). The...

AB1153-HPR Associates of Quality of Life in Patients with Systemic Lupus Erythematosus

BackgroundHealth-related quality of life (HRQoL) represents patient's overall perception of the illness, symptoms severity and treatment impact on physical, emotional and social functions, and became an important complementary source of...

DI-005 Use of belimumab for the treatment of systemic lupus erythematosus in a tertiary level hospital

BackgroundBenlysta is a human monoclonal antibody that is indicated as add-on treatment in adult patients with active, autoantibody-positive (antinuclear antibodies ANA ≥ 1/80) systemic lupus erythematosus (SLE) with a high...

High-Resolution Spectral Domain-Optical Coherence Tomography in Multiple Sclerosis, Part II – the Total Macular Volume. The First Follow-Up Study over 2 Years

Background: Recent studies investigating the use of optical coherence tomography (OCT) in multiple sclerosis (MS) patients have resulted in wide-ranging and often contradictory outcomes. This is mainly due to the complex etiology and heterogeneity of MS, physiological variations in the retinal nerve fiber layer (RNFL) and/or total macular volume (TMV), and limitations in methodology. It remains to be discovered whether any retinal changes in MS develop continuously or in a stepwise fashion, and whether these changes occur in all or a subset of patients. High-resolution spectral domain-OCT devices (SD-OCT) would be required to detect subtle retinal changes and longitudinal studies would have to be carried out to investigate retinal changes over time. In addition, if the hypothesis is correct, then retinal and global brain tissue changes should be detected in a substantial majority of MS patients and detection should be possible with a high degree of disease activity and/or long disease course.Methodology: In order to address the factors above, 37 MS patients (relapsing–remitting, n = 27; secondary progressive, n = 10) were examined prospectively on two occasions with a median interval of 22.4 ± 0.5 months [range 19–27]. SD-OCT was utilized with the Spectralis 3.5 mm circle scan protocol (with locked reference images and eye-tracking mode). None of the patients had optic neuritis 12 months prior to study entry or during the observation period.Principal Findings: The initial TMV pattern differed between study participants, but remained relatively unchanged over the 2-year observation period despite high disease activity or long disease course. The TMV correlated well with the RNFL.Conclusion: The significance of differences in TMV (and RNFL) between study participants remains unclear. Until these differences have been explored further, OCT data in MS patients should be interpreted with caution.

What is the best therapeutic approach if the initial glucocorticoids therapy of active Graves’ orbitopathy fails?

Glucocorticoids are the first-line treatment for active moderate-to-severe and sight-threatening Graves’ orbitopathy. Glucocorticoid therapy, by exerting antiinflammatory and immunomodulatory effects, reduces pain, injection and edema of orbital tissues and provides a substantial relief from optic nerve compression. Although efficiency of both oral and intravenous glucocorticoids is proven, the randomized clinical trials revealed that intravenous therapy is more effective and better tolerated. However, 20-40% of patients respond only partially or do not respond to immunosuppressive treatment. The effectiveness of treatment may be improved by proper selection of patients suspected to have beneficial results, i.e. those with a high degree of disease activity, with orbitopathy of recent onset or recent progression. Corticotherapy may cause major side effects which make treatment continuation impossible. Orbital radiotherapy exerts nonspecific antiinflammatory effect and suppresses radiosensitive lymphocytes infiltrating the orbital space. Orbital radiotherapy remains an effective and safe second-line treatment preferably used in association with glucocorticoids. The combined therapy is more effective than either treatment alone. Sight-threatening Graves’ orbitopathy due to compressive optic neuropathy or corneal ulceration requires immediate intervention. High-dose daily intravenous glucocorticoids are the first-line treatment and if the response is absent or poor within 1-2 weeks the orbital decompression should be performed. Corneal breakdown should be additionally treated with topical lubricants, and sometimes, to provide eyelid closure, with blepharorraphy or tarsorraphy. Unsuccessful oral glucocorticoid treatment of active Graves’ orbitopathy should be an indication for orbital radiotherapy, preferably combined with glucocorticoids, or to a 3 month intravenous methylprednisolone course. If intravenous methylprednisolone was the first treatment and the response is not satisfactory, the intravenous course should be repeated combined with orbital radiotherapy. An alternative approach is combination of oral or intravenous glucocorticoids with cyclosporine for 3-6 months. It was demonstrated that the combined treatment of cyclosporine with oral glucocorticoids resulted in substantial improvement and was useful to reduce the dose of glucocorticoids. In steroid unresponsive Graves’ orbitopathy, biological agents as anti-lymphocyte antibody (anti-CD 20, rituximab) and anti-cytokine antibody (anti-TNFα, etanercept) have shown promise. Theoretically somatostatin analogue pasireotide, with a wider than octreotide or lanreotide binding affinity for various somatostatin receptor subtypes could be also a treatment option. As far as the randomized clinical trials are not available, the use of biological agents and somatostatin analogs is experimental. We hope that the future treatment will be based on pathogenic mechanisms of Graves’ orbitopathy. Small molecule “drug like” TSH receptor neutral antagonists were shown to antagonize TSAb activation of TSH receptor on retroorbital preadipocytes and possibly could be used to treat Graves’ orbitopathy. Currently their effects were determined in the model of orbit cells.

Belimumab: A Guide to Its Use in Systemic Lupus Erythematosus

Belimumab (Benlysta®), a fully human recombinant IgG1λ monoclonal antibody that inhibits the binding of soluble B lymphocyte stimulator to B cells, is indicated for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity despite receiving standard therapy. In multinational trials, significantly more belimumab recipients than placebo recipients achieved an SLE Responder Index response at 52 weeks.

Belimumab

Belimumab is a fully human recombinant IgG1λ monoclonal antibody that inhibits the binding of soluble B lymphocyte stimulator to B cells and hence prevents the survival and differentiation of selected B-cell subsets. It is available in the US, the EU and Canada for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity despite receiving standard therapy. At 52 weeks, a significantly greater proportion of belimumab 10 mg/kg than placebo recipients experienced a response as assessed by the SLE Responder Index (primary endpoint) in the randomized, double-blind, multinational, phase III BLISS-52 and BLISS-76 trials in patients with active seropositive SLE receiving standard therapy. A significantly greater proportion of belimumab than placebo recipients achieved a ≥4 point reduction in the SELENA-SLEDAI score at week 52 in both BLISS trials. However, the SLE Responder Index response rate was not significantly different between belimumab and placebo at 76 weeks in BLISS-76. Belimumab was generally well tolerated in the BLISS trials. During the double-blind periods of these trials and the phase II trial, twice as many deaths were reported with belimumab than placebo (six vs three). There were no meaningful differences between the incidence of serious infections and malignancies with belimumab or placebo.

Clinical analysis of nineteen elderly patients with rheumatoid arthritis

Objective To investigate the clinical features of rheumatoid arthritis (RA) in the aged.Methods The clinical features and inflammatory index of 19 aged patients with RA were retrospectively analyzed and compared with those of 103 young patients with RA. Results The acute onset was ocurred in 11 cases in EORA group(11/19,57.9%) ,32 cases in MRA group (32/103,31.1%), there was sighicant difference two groups (P ＜0. 05). There were 10 cases with intertitial lung disense in EORA group(52.6%) ,27 cases(26.2%) in MRA group.There were no statistical differenes between two groups in erythrocyte sedimentation rate, rheumatoid factor, c-reactive,EORA incidence rate in male and female. Conclusions In comparison with MRA group,the onset of disease in patients of EORA group was more acute than that of MRA,it had higher degree of disease activity. The commonly seen extra-joint manifestation were feeble and interstitial disease lung. Early diagnosis and treatmentof EORA was favor for the prevention of deterioration of this disease. Key words: Arthritis,rheumatoid; Disease attributes; Aged