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ID PMID Title PublicationDate abstract
23977974 A review of cost-effectiveness evaluations as part of national health technology assessmen 2013 Aug Rheumatoid arthritis (RA) is an autoimmune chronic disease which is associated with an increasing disability in patients and high socioeconomic burden. Given the large number of economic evaluations considered by national health technology assessments (HTAs), this review attempts to clarify whether results from biologic disease-modifying antirheumatic drugs (DMARDs) economic evaluations form the basis of official recommendation by national HTA agencies in Australia, Canada, Scotland and England. The results show that evidence of cost-effectiveness was not equally perceived by decision makers and did not have equal weightage in defining the official listing of biologic DMARDs for the treatment of RA. As it has been demonstrated in previous studies, major barriers exist for the integration of cost-effectiveness and cost-utility results with national HTA activity. In fact, as shown in this review, even when such analysis are available, cost-minimization and comparative effectiveness studies seemed to be preferred by some HTA agencies as tools to inform allocation of healthcare resources.
24839607 Treatment comparison in rheumatoid arthritis: head-to-head trials and innovative study des 2014 Over the last decades, the increasing knowledge in the area of rheumatoid arthritis has progressively expanded the arsenal of available drugs, especially with the introduction of novel targeted therapies such as biological disease modifying antirheumatic drugs (DMARDs). In this situation, rheumatologists are offered a wide range of treatment options, but on the other side the need for comparisons between available drugs becomes more and more crucial in order to better define the strategies for the choice and the optimal sequencing. Indirect comparisons or meta-analyses of data coming from different randomised controlled trials (RCTs) are not immune to conceptual and technical challenges and often provide inconsistent results. In this review we examine some of the possible evolutions of traditional RCTs, such as the inclusion of active comparators, aimed at individualising treatments in real-life conditions. Although head-to-head RCTs may be considered the best tool to directly compare the efficacy and safety of two different DMARDs, surprisingly only 20 studies with such design have been published in the last 25 years. Given the recent advent of the first RCTs truly comparing biological DMARDs, we also review the state of the art of head-to-head trials in RA.
23774902 The influence of ageing on the development and management of rheumatoid arthritis. 2013 Oct The population of elderly individuals with rheumatoid arthritis (RA) is expanding, due mainly to increasing life expectancy. A variety of theories have been proposed to explain the ageing process, including accumulation of DNA damage and resultant changes in biological processes. Such changes can influence the development and/or course of disease. Furthermore, alterations in biological function determine the biological age-as opposed to chronological age-of an individual, which strongly influences their ability to cope with disease. Moreover, comorbidities are more frequent in elderly individuals. Together, these factors complicate treatment of disease and necessitate careful patient management. Indeed, although evidence from clinical trials suggests that DMARDs and biologic agents have good efficacy and are well tolerated in elderly patients with RA, such individuals are often undertreated and inadequately managed. Unfortunately, insufficient data are available for the development of evidence-based guidelines for this population, as elderly patients are often excluded from clinical trials owing to age restrictions or comorbidities. Thus, additional clinical studies in elderly patients are warranted, with treatment regimens tailored according to vitality or frailty parameters. This Review focuses on the pathophysiological aspects of ageing and their implications for the management of RA in elderly patients.
24788818 Analysis of differentially expressed genes between rheumatoid arthritis and osteoarthritis 2014 Jul The aim of the current study was to investigate disease-associated genes and related molecular mechanisms of osteoarthritis (OA) and rheumatoid arthritis (RA). Using GSE7669 datasets downloaded from Gene Expression Omnibus databases, the differentially expressed genes (DEGs) between RA and OA synovial fibroblasts (SFBs) (n=6 each) were screened. DEG-associated co-expression and topological properties were analyzed to determine the rank of disease-associated genes. Specifically, the fold change of differentially expressed genes, the clustering coefficient and the degree of differential gene co-expression were integrated to determine the disease-associated gene ranking. The underlying molecular mechanisms of these crucial disease-associated genes were investigated by gene ontology (GO) enrichment analysis. A total of 1313 DEGs, including 1068 upregulated genes and 245 downregulated genes were observed. The top 20 disease-associated genes were identified, including proteoglycan 4, inhibin β B, carboxypeptidase M, alcohol dehydrogenase 1C and integrin β2. The major GO biological processes of these top 20 disease-associated genes were highly involved in the immune system, such as responses to stimuli, immune responses and inflammatory responses. This large-scale gene expression study observed disease-associated genes and their associated GO function in RA and OA, which may provide opportunities for biomarker development and novel insights into the molecular mechanisms of these two diseases.
24018548 Rheumatoid arthritis: stress affects rheumatoid arthritis, but via what mechanisms? 2013 Oct The mind and body are thought to interact in a manner that influences health, but modelling the right aspects of each so as to best inform treatment is a tricky proposition. A new study discusses how stress can affect rheumatoid arthritis symptoms.
24204584 Measles contributes to rheumatoid arthritis: evidence from pathway and network analyses of 2013 Growing evidence from epidemiological studies indicates the association between rheumatoid arthritis (RA) and measles. However, the exact mechanism for this association is still unclear now. We consider that the strong association between both diseases may be caused by shared genetic pathways. We performed a pathway analysis of large-scale RA genome-wide association studies (GWAS) dataset with 5,539 cases and 20,169 controls of European descent. Meanwhile, we evaluated our findings using previously identified RA loci, protein-protein interaction network and previous results from pathway analysis of RA and other autoimmune diseases GWAS. We confirmed four pathways including Cytokine-cytokine receptor interaction, Jak-STAT signaling, T cell receptor signaling and Cell adhesion molecules. Meanwhile, we highlighted for the first time the involvement of Measles and Intestinal immune network for IgA production pathways in RA. Our results may explain the strong association between RA and measles, which may be caused by the shared genetic pathway. We believe that our results will be helpful for future genetic studies in RA pathogenesis and may significantly assist in the development of therapeutic strategies.
24764355 Age-related diagnostic utility of rheumatoid factor, anticyclic citrullinated peptide and 2014 Jun OBJECTIVES: Retrospective study to evaluate the diagnostic utility of rheumatoid factor (RF), anticyclic citrullinated peptide antibodies (ACPA) and antikeratin antibodies (AKA) in a broad age range of patients with rheumatoid arthritis (RA). METHODS: Clinical and serological data from patients with RA were collected and analysed. Patients were stratified according to age (<16 years [juvenile idiopathic arthritis; JIA], 16-40 years; 41-60 years and >60 years) and sex. RESULTS: The study included 3725 patients. There were no significant sex-related differences in rates of RF, ACPA or AKA positivity. RF, ACPA and AKA positivity were significantly less common in patients aged <16 years than those aged ≥ 16 years. There were no other significant differences between age groups. CONCLUSIONS: RF, ACPA and AKA have better diagnostic value for RA in adult patients than in patients with JIA. A combination of RF, ACPA and AKA serological testing may be a useful diagnostic tool for RA in Chinese adults.
25304188 Validation of the 2010-ACR/EULAR -classification criteria using newly EULAR-defined erosio 2015 Jan OBJECTIVE: To validate the 2010-ACR/EULAR criteria for rheumatoid arthritis (RA), taking into account the recent EULAR definition of "erosive disease", on the 310 patients comprising the very early arthritis cohort (VErA). METHODS: 2010-criteria performances were tested by first strictly applying its three items successively: ≥ 1 clinical synovitis/another disease(s)/score ≥ 6/10), then the typical erosion grid without obtaining a score of ≥ 6 to diagnose RA. We tested successively: no erosion (S1), ≥ 1 erosion(s) (S2), EULAR-defined erosive disease (S3). Two gold standards were used: expert diagnosis at six years and EULAR erosive disease at two years. RESULTS: At inclusion, median age was 52 years; median RA duration 4.2 months. 2010-ACR/EULAR criteria, including EULAR-defined erosive disease applied at baseline, classified comparable numbers of patients as the 1987 criteria (P=0.27). Using expert diagnosis at six years, more patients were classified as RA with S2 than 1987-ACR criteria (P<0.04). In contrast, sensitivity and specificity indicated that 2010-ACR/EULAR-S3 criteria performed slightly but not significantly better than 1987-ACR criteria. On ROC curves, a score ≥ 6 correctly classified RA. When EULAR-defined erosion at two years was the gold standard, the 1987-ACR, the 2010-S1, -S2 and -S3 criteria performed comparably. CONCLUSIONS: Using the very early community-based, conservatively treated VErA cohort, the strict application of 2010-ACR/EULAR criteria using the new EULAR definition of erosive disease or not performed slightly but not significantly better than the 1987-ACR criteria.
24777468 Presence of power Doppler synovitis in rheumatoid arthritis patients with synthetic and/or 2014 Aug The aim of this study was to evaluate the ultrasonographic synovitis in rheumatoid arthritis (RA) patients who reached clinical remission. Two hundred and two RA patients were enrolled into this study. One hundred and eleven RA patients achieved clinical remission with the treatment of synthetic and/or biologic disease-modifying anti-rheumatic drugs (DMARDs). Subclinical synovitis was assessed by power Doppler ultrasonography (PDUS). PD synovitis was semi-quantitatively recorded. Twenty-two joint regions were imaged: bilateral wrists, metacarpophalangeal (MCP) joints, and proximal interphalangeal (PIP) joints. PD remission was defined as a total PD score of 0. The subclinical synovitis in the RA patients who achieved clinical remission was evaluated. The correlations between PD total scores and clinical/laboratory parameters were analyzed. Among the 111 RA patients who achieved clinical remission, 110 (99.1 %), 67 (60.4 %), 55 (49.5 %), 50 (45.0 %), and 54 (48.6 %) patients, respectively, satisfied DAS28 (CRP), DAS28 (ESR), CDAI, SDAI, and 2010 ACR/EULAR remission criteria. However, only 54 (48.6 %) patients achieved PD remission. Subclinical synovitis was detectable in 57 (51.8 %), 30 (44.8 %), 22 (40.0 %), 19 (38.0 %), and 18 (33.3 %) patients accordingly. On the contrary, 11 (26.8 %) out of 41 patients who fulfilled all five clinical remission criteria had evidence of subclinical synovitis. In those 91 patients who did not achieved clinical remission, total PD score was correlated with swollen joint counts (SJC), tender joint counts (TJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complex disease activity indexes (P < 0.01), but not the titers of rheumatoid factor and anti-cyclic citrullinated peptide. Among those 57 patients with subclinical synovitis after reaching clinical remission, no correlation was found between PD total score and SJC, TJC, ESR, CRP, and complex disease activity indexes. Presence of subclinical synovitis is common in patients achieving clinical remission. The stricter clinical remission criteria may reflect less PD synovitis. In patients with active RA, PD total score of synovitis was positively correlated with disease activity.
24321439 High pain catastrophizing scores in one-fourth of patients on biotherapy for spondylarthri 2014 May OBJECTIVES: To measure catastrophizing scores in patients on biotherapy for spondyloarthritis (SpA) or rheumatoid arthritis (RA). METHODS: The first 140 outpatients or day-hospital patients seen at a teaching hospital rheumatology department for biotherapy administration completed the validated French version of the Pain Catastrophizing Scale (PCS, total score ranging from 0 to 52); a questionnaire on perceived support and past, current, and future disease activity; and a questionnaire on perceived understanding of their disease by family and co-workers. RESULTS: PCS scores were significantly higher in the 54 SpA patients than in the 86 RA patients (20.8 ± 12.1 versus 17.0 ± 13.6; P = 0.08), as a result of a higher helplessness subscore (10.0 ± 6.2 versus 7.8 ± 6.2; P = 0.046). The PCS score was ≥30 in 14/54 (26%) SpA patients and in 19/86 (22%) RA patients; physicians identified catastrophizing in only 17 of these 33 patients. PCS scores showed moderate correlations with the AS-DAS and DAS-28 and slightly stronger correlations with the overall pain score (Pearson, +0.431; P = 0.0001). SpA patients reported significantly worse understanding by their co-workers than did RA patients (33.9 ± 33.4 versus 53.9 ± 36.3; P = 0.007). CONCLUSION: One-fourth of patients with SpA or RA had very high pain catastrophizing scores despite biotherapy. Pain catastrophizing was missed by the physicians in half the cases and was relatively independent from other follow-up parameters. Pain catastrophizing can jeopardize treatment outcomes and deserves specific management.
23958376 Items and dimensions for the construction of a multidimensional computerized adaptive test 2013 Oct OBJECTIVES: Development of an item pool to construct a future computerized adaptive test (CAT) for fatigue in rheumatoid arthritis (RA). The item pool was based on the patients' perspective and examined for face and content validity previously. This study assessed the fit of the items with seven predefined dimensions and examined the item pool's dimensionality structure in statistical terms. STUDY DESIGN AND SETTING: A total of 551 patients with RA participated in this study. Several steps were conducted to come from an explorative item pool to a psychometrically sound item bank. The item response theory (IRT) analysis using the generalized partial credit model was conducted for each of the seven predefined dimensions. Poorly fitting items were removed. Finally, the best possible multidimensional IRT (MIRT) model for the data was identified. RESULTS: In IRT analysis, 49 items showed insufficient item characteristics. Items with a discriminative ability below 0.60 and/or model misfit effect sizes greater than 0.10 were removed. Factor analysis on the 196 remaining items revealed three dimensions, namely severity, impact, and variability of fatigue. The dimensions were further confirmed in MIRT model analysis. CONCLUSION: This study provided an initially calibrated item bank and showed which dimensions and items can be used for the development of a multidimensional CAT for fatigue in RA.
23606704 Measurement error in the assessment of radiographic progression in rheumatoid arthritis (R 2014 Jun OBJECTIVES: To evaluate if the mean smallest detectable change (SDC) of multiple time intervals using the Bland & Altman (B&A) levels of agreement (LoA) method is an appropriate surrogate for the generalisability analysis method for estimating the overall SDC of radiological progression in rheumatoid arthritis (RA) trials. Secondly, to compare the SDC based on 95% LoA with the SDC based on 80% LoA, and to investigate the association between SDC and baseline damage and progression. METHODS: Fifteen datasets from randomised controlled trials in RA were scored by 13 experienced readers as pairs according to the modified Sharp/van der Heijde method. The SDC using the 95% and 80% LoA and the generalisability methods was calculated. RESULTS: 21 295 radiographic time points from 7643 patients were included. The mean (range) SDC for the LoA and the generalisability methods was 3.1 (2.3-4.3) and 3.2 (2.3-4.6) units, respectively. The mean ± SD difference between the two methods was -0.13 ± 0.28. The mean SDC including all intervals (n=31) was 3.0 ± 0.7 for 95% LoA and 2.0 ± 0.4 for 80% LoA. No relationship was observed between baseline damage and the SDC, whereas the SDC increased with increasing radiological progression. CONCLUSIONS: The mean of the interval SDCs obtained by the simple LoA method is a valid surrogate for the SDC obtained by complex generalisability methods. The SDC depends on the level of radiographic progression rather than on the level of absolute damage. In addition, the use of an SDC based on 80% rather than on 95% LoA is proposed.
24952308 A systematic review into the effectiveness of hand exercise therapy in the treatment of rh 2014 Nov Hand exercises are often part of the treatment of hand rheumatoid arthritis; however, it is still unclear whether and what type of exercises is effective in the treatment of this condition. Therefore, a systematic review into the effectiveness of hand exercises in the treatment of hand rheumatoid arthritis has been performed. Studies were identified in the literature databases by predefined search criteria. The eight included studies are peer-reviewed studies published between 2000 and 2014. Hand exercises differed between studies, but always included resistance and/or active range of motion exercises. Grip strength in various grip types (power grip, key pinch, precision pinch and tripod pinch) was found to improve by hand exercise therapy without having adverse effects on pain or disease activity. Adaptations in the range of motion in response to hand exercise therapy were less pronounced. There appears to be some transfer from the improvements on the body functioning level to the level of daily functioning, with the largest improvements found on grip ability. With regard to the intervention content, there was some evidence in favour of a longer therapy duration and a higher therapy intensity. No conclusions could be drawn on the effectiveness of the different types of exercises. Collectively, the studies indicate that hand exercises may have positive effects on strength and some aspects of daily functioning without aggravating disease activity or pain, although caution should be taken for subjects in the exacerbation period.
23859555 Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis 2013 Rheumatoid arthritis (RA) is a chronic inflammatory disease in which the progressive destruction of joint causes morbidity. It is also associated with an increased risk of atherosclerosis, which can result in cardiovascular disease and mortality. The therapeutic goal is to control the systemic inflammation to obtain not only the remission of symptoms, but also improve general state of health. Although recent biologic immunosuppressive therapies targeting pro-inflammatory cytokines have spawned a paradigm shift regarding the prognosis of RA, these therapies possess inherent side effects. Also, early diagnosis of the disease remains confounded by uncertainty. While the mechanisms responsible for the onset of RA remain unclear, reactive oxygen species (ROS) play a significant role in the pathogenesis of RA. ROS play a central role both upstream and downstream of NF-κB and TNFα pathways, which are located at the center of the inflammatory response. Among the ROS, the hydroxyl radical is the most harmful, and molecular hydrogen (H2) is a selective scavenger for this species. Recently, it has been shown that H2 is useful when administered along with the conventional therapy in RA as it acts to reduce oxidative stress in the patients. Especially in the early stage, H2 showed significant therapeutic potential, which also seemed to assist diagnosis and treatment decisions of RA. The possible expectations regarding the potential benefits of H2 by reducing the oxidative stress, resulting from inflammatory factors, are raised and discussed here. They include prevention of RA and related atherosclerosis, as well as therapeutic validity for RA.
25329103 Rheumatoid myositis, myth or reality? A clinical, imaging and histological study. 2014 Rheumatoid myositis (RM) is still poorly characterized, albeit the concept of muscle involvement in rheumatoid arthritis (RA) is well-recognized as being driven by a wide range of causes including inflammation, drugs, impaired joint flexibility, sedentarism. OBJECTIVE: To describe clinical, serological, imaging and histological pattern of RM. MATERIALS AND METHODS: This is a retrospective study on eight RM selected from a cohort of one hundred and three RA systematically assessed for skeletal muscle involvement. Data collected included clinical, serum muscle enzymes, muscle imaging and biopsy (Hematoxylin-Eosin, modified Gömöri trichrome staining). RESULTS: Routine muscle histology indicated both non-specific muscle fiber damage (changes in fiber size and internal structure: pleomorphic mitochondria, dilated sarcotubular system, multiple internal or subsarcommal nuclei; abnormal fiber types distribution: trend towards type II; atrophy; degenerative/regenerative modifications) and the presence of inflammatory deposits in all patients (mild to moderate, patchy B- and T-cells infiltrates, mainly perivascular and endomysial, but also in the perimysial region classified as polymyositis-like deposits). High levels of serum muscle enzymes, abnormal EMG (short duration, small amplitude, polyphasic motor unit action potentials) without insertional activity and fibrillations, active inflammation on both Doppler ultrasound and MRI were commonly reported. CONCLUSIONS: Traditional analysis of muscle biopsy specimens (Hematoxylin-Eosin, modified Gömöri trichrome staining) is faraway unsatisfactory, only documenting changes in muscle fibers size, architecture, internal structure, and, possibly, detecting perivascular, perimysial or endomysial inflammatory deposits. Upcoming research should address the value of muscle imaging for the diagnosis and evaluation of treatment response and muscle function in rheumatoid myositis.
23213198 In vivo imaging of cell proliferation enables the detection of the extent of experimental 2013 Jan The aim of this work was to study the feasibility of measuring cell proliferation noninvasively in vivo during different stages of experimental arthritis using the PET proliferation tracer 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT). METHODS: We injected mice with serum containing glucose-6-phosphate-isomerase-specific antibodies to induce experimental arthritis, and we injected control mice with control serum. Animals injected with (18)F-FLT 1, 3, 6, and 8 d after the onset of disease were analyzed in vivo by PET, PET/CT, or PET/MR imaging followed by autoradiography analysis. The (18)F-FLT uptake in the ankles and forepaws was quantified on the basis of the PET images by drawing standardized regions of interest. To correlate the in vivo PET data with cell proliferation, we performed Ki-67 immunohistochemistry of diseased and healthy joints at the corresponding time points. RESULTS: Analysis of the different stages of arthritic joint disease revealed enhanced (18)F-FLT uptake in arthritic ankles (2.2 ± 0.2 percentage injected dose per gram [%ID/g]) and forepaws (2.1 ± 0.3 %ID/g), compared with healthy ankles (1.4 ± 0.3 %ID/g) and forepaws (1.5 ± 0.5 %ID/g), as early as 1 d after the glucose-6-phosphate-isomerase serum injection, a time point characterized by clear histologic signs of arthritis but only slight ankle swelling. The (18)F-FLT uptake in the ankles (3.5 ± 0.3 %ID/g) reached the maximum observed level at day 8. Ki-67 immunohistochemical staining of the arthritic ankles and forepaws revealed a strong correlation with the in vivo (18)F-FLT PET data. PET/CT and PET/MR imaging measurements enabled us to identify whether the (18)F-FLT uptake was located in the bone or the soft tissue. CONCLUSION: Noninvasive in vivo measurement of cell proliferation in experimental arthritis using (18)F-FLT PET is a promising tool to investigate the extent of arthritic joint inflammation.
25365085 An evidence-based approach to laboratory tests in usual care of patients with rheumatoid a 2014 Sep Laboratory tests often are regarded as the most important information in clinical care by patients and doctors, and dominate clinical decisions in many chronic diseases such as diabetes and hyperlipidemia. Most patients with rheumatoid arthritis (RA) have a positive test for rheumatoid factor or anti-cyclic citrullinated peptide antibodies (ACPA), or an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). However, about a third of RA patients, have negative tests for rheumatoid factor or ACPA, and more than 40% have a normal ESR or CRP at presentation ('false-negative' results). Furthermore, many normal people have a positive test for rheumatoid factor or ACPA but do not have RA, even among those with extensive musculoskeletal pain ('false-positive' results). Abnormal laboratory tests are the most significant predictor of high levels of radiographic progression, and therefore regarded as indicators of 'poor prognosis RA'. By contrast, laboratory tests are far less predictive of severe long-term outcomes such as work disability and premature mortality than functional difficulties reported on a patient questionnaire. A patient questionnaire score is abnormal in 89% of RA patients at presentation, and therefore more useful than ESR or CRP to document subsequent clinical improvement or deterioration. In clinical practice, patient questionnaire scores and RAPID3, an index of physical function, pain, and patient global estimate of status, identify incomplete responses to methotrexate more effectively than ESR. Improved understanding of the limitations of laboratory tests in diagnosis and management of individual patients with RA (and all rheumatic diseases) could improve patient care and outcomes.
24131467 A retrospective chart review of the use of rituximab for the treatment of rheumatoid arthr 2014 Sep AIM: Rituximab is one of nine biologic agents approved for the treatment of rheumatoid arthritis (RA) in Australia. The primary study objective was to analyze the factors that lead to the therapeutic decision to use rituximab in RA. METHOD: A cross-sectional, retrospective chart review was conducted to identify patients who were treated with rituximab and to evaluate their response to treatment. RESULTS: Factors influencing the prescription of rituximab were identified. The most commonly reported reason for prescribing rituximab was the presence of comorbidities and the presence of seropositive disease. Median rituximab treatment duration was 32.5 months and mean number of treatment cycles was 4.1. Disease activity scores showed significant improvement from baseline to most recent visit. Rituximab treatment was well-tolerated in this group of RA patients. CONCLUSIONS: Rituximab was effective in a refractory group of RA patients and appears to be safe in a population with a high prevalence of comorbidities, including malignancy and recurrent infections/bronchiectasis. This study may assist rheumatologists in selecting appropriately targeted therapy in RA.
24340741 [The role of biomarkers in diagnostics and forecasting of effectiveness of modern therapy 2013 Aug The rheumatoid arthritis is one of the most severe and widespread systemic inflammatory autoimmune diseases. The modern laboratory diagnostic of rheumatoid arthritis includes detection of large spectrum of biomarkers (autoantibodies, indicators of acute phase of inflammation, cytokines, markers of activation of endothelium, subpopulations of lymphocytes, products of metabolism of bone and cartilaginous tissue, genetic markers) in blood, synovial fluid, and synovial tissue. Alongside with common techniques of immunodiagnostics, the multiplex analysis of biomarkers based on genetic, transcript and proteomic technologies is applied. The results of identification of biomarkers are an important instrument of early diagnostics, activity evaluation, severity of disease course and disease prognosis and effectiveness of applied therapy. Among biomarkers associated with rheumatoid arthritis the most clinical value have antibodies (rheumatoid factor class IgM, antibodies to citrullinized proteins) and acute phase indicators (erythrocyte sedimentation rate, C-reactive protein) which are diagnostic criteria of rheumatoid arthritis and can be used in evaluation of prognosis of this disease. On basis of multi-parametric analysis of 12 key proteins of blood serum the new index of activity of rheumatoid arthritis (Vectra DA) is developed Nowadays, the potential biomarkers are detected providing to implement immunologic monitoring and prognosis of effectiveness of therapy of rheumatoid arthritis with genetic engineering biologic preparations. The laboratory tests are developed to evaluate immunogenicity of genetic engineering biologic preparations and diagnostic of latent tuberculosis infection in patients with rheumatoid arthritis against the background of therapy with using this group of pharmaceuticals.
24863583 High serum level of haptoglobin is associated with the response of 12 weeks methotrexate 2016 May BACKGROUND: We previously found, using microarray, haptoglobin (HP) expression signal was 5.1-fold increased in peripheral blood mononuclear cells (PBMCs) from methotrexate (MTX)-resistant rheumatoid arthritis (RA) patients. OBJECTIVES: To investigate whether serum levels of HP are associated with the response of 12 weeks MTX therapy in recent-onset RA patients. METHODS: Sixty-nine active RA patients with recent onset (< 24 months) were treated with MTX. Clinical variables, levels of HP messenger RNA (mRNA) in PBMCs and HP serum levels were tested at week 0 and week 12. RESULTS: After 12 weeks of MTX treatment, 34.7% of RA patients were categorized as responders according to European League Against Rheumatism (EULAR) response criteria (Week 12 Disease Activity Score of 28 joints [DAS-28] ≤ 3.2 and decrease > 1.2) and all others (65.2%) were defined as non-responders. The baseline HP mRNA in PBMCs from non-responders is significantly higher than those in responders (P < 0.05). Similar to mRNA expression, non-responders showed significantly elevated serum HP levels at baseline (369.9 ± 159.8 mg/dL) compared to those in responders (255.3 ± 143.9 mg/dL) (P = 0.01). Serum HP levels were decreased significantly from 255.3 ± 143.9 mg/dL at baseline to 186.4 ± 108.5 mg/dL at week 12 (P = 0.04) in responders, but remained at high levels in non-responders. CONCLUSIONS: High serum levels of HP at baseline are associated with inadequate response of 12 weeks MTX treatment in recent-onset RA patients. Further replication studies in larger samples are needed to validate HP as a potential predictive biomarker for response to MTX therapy in RA.