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ID PMID Title PublicationDate abstract
25542800 Novel multimeric IL-1 receptor antagonist for the treatment of rheumatoid arthritis. 2015 Feb Protein therapeutics targeting inflammatory mediators have shown great promise for the treatment of autoimmunities such as rheumatoid arthritis (RA). However, a significant challenge in this area has been their low in vivo stability and consequently their severely compromised therapeutic efficacy. One such therapeutic molecule IL-1 receptor antagonist (IL-1ra), used in the treatment of rheumatoid arthritis, has displayed only modest efficacy in human clinical trials owing to its short biological half-life. Herein, we report a novel approach to conglomerate individual protein entities into a drug depot by incorporation of an amyloidogenic motif Lys-Phe-Phe-Glu (KFFE) thereby dramatically improving their systemic persistence and in turn their therapeutic efficacy in a mice model of autoimmune arthritis.
25523984 Factors associated with sustained remission in patients with rheumatoid arthritis. 2015 Jul OBJECTIVE: To find out the factors that are associated with sustained remission measured by DAS28 and boolean ACR EULAR 2011 criteria at the time of diagnosis of rheumatoid arthritis. MATERIALS AND METHODS: Medical records of patients with rheumatoid arthritis in sustained remission according to DAS28 were reviewed. They were compared with patients who did not achieved values of DAS28<2.6 in any visit during the first 3 years after diagnosis. We also evaluated if patients achieved the boolean ACR/EULAR criteria. Variables analyzed: sex, age, smoking, comorbidities, rheumatoid factor, anti-CCP, ESR, CRP, erosions, HAQ, DAS28, extra-articular manifestations, time to initiation of treatment, involvement of large joints, number of tender joints, number of swollen joints, pharmacological treatment. RESULTS: Forty five patients that achieved sustained remission were compared with 44 controls. The variables present at diagnosis that significantly were associated with remission by DAS28 were: lower values of DAS28, HAQ, ESR, NTJ, NSJ, negative CRP, absence of erosions, male sex and absence of involvement of large joints. Only 24.71% achieved the boolean criteria. The variables associated with sustained remission by these criteria were: lower values of DAS28, HAQ, ESR, number of tender joints and number of swollen joints, negative CRP and absence of erosions. CONCLUSION: The factors associated with sustained remission were the lower baseline disease activity, the low degree of functional disability and lower joint involvement. We consider it important to recognize these factors to optimize treatment.
24758843 [The golden age of rheumatoid arthritis treatment]. 2014 Mar Today, we enjoy the golden age of rheumatology. In the 1970s, the paradigm for treating rheumatoid arthritis consisted in a pyramid. In the decade of the 1980s, and shortly after began a revolution in the understanding and treatment of rheumatic diseases. Methotrexate and tumor necrosis factor-blockers came on the scene.
25307208 Evaluation of clinical and cytogenetic parameters in rheumatoid arthritis patients for eff 2015 Jan 15 BACKGROUND: Rheumatoid arthritis is the commonest inflammatory joint disease, affecting nearly 1% of the adult population worldwide. Early and accurate diagnosis and prognosis of rheumatoid arthritis (RA) have become increasingly important. In the present study, we aimed to elucidate the relationships between hematological, biochemical, immunological and cytogenetic parameters in rheumatoid arthritis patients and healthy normal controls. METHODS: The study group comprised of 126 RA patients and equal number of healthy normal control subjects. The blood was collected and analyzed for biochemical, immunological, enzymatic and cytogenetic parameters. RESULTS: Results of the present study indicated that 20% of RA patient's hematological, 31% of biochemical and 70% immunological parameters had a significant difference from the controls and reference range. The RF and anti-CCP antibody levels were also positive in 70% of RA patients. A significant increase in minor chromosomal abnormalities was also observed in patients as compared to controls. CONCLUSION: The knowledge about autoimmune diseases is very low among the South Indian population. The present study has thus helped in understanding the RA disease in a better way based on a pattern of various clinical markers of the disease condition which might help in planning therapeutic intervention strategies and create awareness about the disease management among RA patients of the population studied.
24089231 Regulation different network analysis of rheumatoid arthritis (RA) and osteoarthritis (OA) 2013 Sep BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis that progresses to destruction of cartilage and bone. AIM: The purpose of this study was to employ microarray analysis combined with bioinformatics techniques to evaluate differential gene expression in BM-derived mononuclear cells obtained from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) to study the pathogenesis of this disease. MATERIALS AND METHODS: Gene expression profiles in BM-derived mononuclear cells from 9 RA and 10 OA patients were obtained from GEO. RESULTS: The bone marrow (BM) mononuclear cells showed 2581 up-regulated and 649 down-regulated genes in RA patients relative to the OA group: Our analysis indicated that several differentially expressed genes might play crucial roles in RA development, including SP1, RARA, ETS1, ETS2, FOS and ESR1. CONCLUSIONS: Further analysis predicted these genes might be involved in RA through cancer related pathways and immunity related pathways. Furthermore, these genes may serve as novel therapeutic targets for the treatment of RA.
23986467 Effect of rocker shoes on pain, disability and activity limitation in patients with rheuma 2014 Aug BACKGROUND: Rheumatoid arthritis is a chronic inflammatory joint disease which affects the joints and soft tissues of the foot and ankle. Rocker shoes may be prescribed for the symptomatic foot in rheumatoid arthritis; however, there is a limited evidence base to support the use of rocker shoes in these patients. OBJECTIVES: The aim of this study was to evaluate the effectiveness of heel-to-toe rocker shoes on pain, disability, and activity limitation in patients with rheumatoid arthritis. STUDY DESIGN: Clinical trial. METHODS: Seventeen female patients with rheumatoid arthritis of 1 year or more duration, disease activity score of less than 2.6, and foot and ankle pain were recruited. Heel-to-toe rocker shoe was made according to each patient's foot size. All the patients were evaluated immediately, 7 and 30 days after their first visit. Foot Function Index values were recorded at each appointment. RESULTS: With the use of rocker shoes, Foot Function Index values decreased in all subscales. This reduction was noted in the first visit and was maintained throughout the trials. CONCLUSION: Rocker shoe can improve pain, disability, and activity limitation in patients with rheumatoid foot pain. All the subjects reported improved comfort levels. CLINICAL RELEVANCE: The results of this study showed that high-top, heel-to-toe rocker shoe with wide toe box was effective at reducing foot and ankle pain. It was also regarded as comfortable and acceptable footwear by the patients with rheumatoid foot problems.
24599792 Filaggrin peptides with β-hairpin structure bind rheumatoid arthritis antibodies. 2014 Apr 7 In the early detection of rheumatoid arthritis (RA) synthetic filaggrin peptides serve as antigens for rheumatoid-specific autoantibodies (anti-citrullinated peptide antibody, ACPA) in ELISA tests. In this work we present a peptide that exhibits the binding epitope of ACPA in the form of a stable folding β-hairpin. The homogeneity of the peptide folding was confirmed by NMR spectroscopy and might lead to the first proposed structure of the antibody-bound conformation of the epitope.
24611763 Effects of surgical intervention on disease activity of rheumatoid arthritis: cases of sur 2014 Jul OBJECTIVES: In order to verify combination therapy with drugs and surgery for rheumatoid arthritis (RA), we evaluated changes in clinical outcome affected by surgical intervention in the patient treated with biologics and investigated the effects of surgery on disease activity. METHODS: Fifty-five lower limb joint surgeries were performed in 48 patients under biological therapy. DAS28-ESR, modified Health Assessment Questionnaire (mHAQ) score, PtGA and serum CRP were examined just before surgery, at 6 months and at 12 months after surgery. A kind of suitable medication and its dose were investigated. RESULTS: Preoperative DAS28-ESR significantly decreased from 3.71 ± 1.19 (mean ± SD) to 3.37 ± 1.22 at 6 months and to 3.24 ± 1.05 at 12 months postoperatively. mHAQ score did not change, but, PtGA and serum CRP improved. In 43 (78.2%) patients in whom no change or decrease in medication during the follow-up period, excluding the effect of drugs, DAS28-ESR also decreased significantly from 3.53 ± 1.17 to 3.16 ± 1.16 at 6 months, and to 3.16 ± 0.98 at 12 months. CONCLUSIONS: Lower limb surgery performed under biological therapy enhances the effects of not only improving joint function but also of ameliorating systemic disease activity.
24251814 Ultrasound evaluation of the effects of leukocytapheresis on rheumatoid arthritis. 2014 Oct Leukocytapheresis (LCAP) is effective in treating rheumatoid arthritis (RA). Ultrasound (US) examination of joints is useful for evaluating disease activity and therapeutic effects in RA, but the clinical assessment of LCAP therapy with US has been little reported. We investigated the usefulness of US for evaluating the effects of LCAP in patients with RA. US examination was performed in six patients (total of seven cases) who underwent LCAP. Twenty-eight joints (bilateral shoulders, elbows, wrists, 1st to 5th metacarpophalangeal joints, 1st to 5th proximal interphalangeal joints, and knee joints) were evaluated by a systematic multiplanar grey-scale and power Doppler (PD) examination. Disease activity of RA was evaluated using the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). Moderate or good responses to LCAP based on the DAS28-ESR were observed in four of the seven cases although C-reactive protein (CRP) and ESR did not decrease. LCAP significantly reduced the mean total PD score 17.3 ± 11.6 to 13.0 ± 10.5 (P = 0.0469). The total PD score decreased in six of the seven cases, and the number of joints with PD score ≥ 2 decreased in five of the seven cases. The rate of decrease in the number of joints with PD score ≥ 2 correlated strongly with the DAS28-ESR and its components, especially swollen joint counts and evaluator's global assessment, but not with the rate of decrease in CRP and ESR. US imaging of joints may be useful for evaluating the therapeutic effects of LCAP on RA compared to other inflammatory parameters.
24559487 Effect of intermittent aerobic exercise on sleep quality and sleep disturbances in patient 2014 Feb 21 BACKGROUND: Poor sleep is prevalent in patients with systemic inflammatory disorders, including rheumatoid arthritis, and, in addition to fatigue, pain, depression and inflammation, is associated with an increased risk of co-morbidity and all-cause mortality. Whereas non-pharmacological interventions in patients with rheumatoid arthritis have been shown to reduce pain and fatigue, no randomized controlled trials have examined the effect of non-pharmacological interventions on improvement of sleep in patients with rheumatoid arthritis. The aim of this trial was to evaluate the efficacy of an intermittent aerobic exercise intervention on sleep, assessed both objectively and subjectively in patients with rheumatoid arthritis. METHODS/DESIGN: A randomized controlled trial including 44 patients with rheumatoid arthritis randomly assigned to an exercise training intervention or to a control group. The intervention consists of 18 session intermittent aerobic exercise training on a bicycle ergometer three times a week. Patients are evaluated according to objective changes in sleep as measured by polysomnography (primary outcome). Secondary outcomes include changes in subjective sleep quality and sleep disturbances, fatigue, pain, depressive symptoms, physical function, health-related quality of life and cardiorespiratory fitness. DISCUSSION: This trial will provide evidence of the effect of intermittent aerobic exercise on the improvement of sleep in patients with rheumatoid arthritis, which is considered important in promotion of health and well-being. As such, the trial meets a currently unmet need for the provision of non-pharmacological treatment initiatives of poor sleep in patients with rheumatoid arthritis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01966835.
23370853 Anti-citrullinated protein antibodies: role in pathogenesis of RA and potential as a diagn 2013 Jul Rheumatoid arthritis is an autoimmune disorder which involves inflammation of the synovial tissue, leading to synovial proliferation, bone erosion and ultimately joint disability. It is a complex disorder, and the proper etiology is still unknown. Both environmental and genetic factors are responsible for the development of rheumatoid arthritis. Clinically, the disease is generally diagnosed by the presence of auto-antibodies like rheumatoid factor. But these are not specifically associated with rheumatoid arthritis. These are also present in patients with other autoimmune disorders and also in healthy persons. Citrullinated epitopes are shown to be more specific for rheumatoid arthritis. Citrullination normally occurs in cells undergoing apoptosis, and hence, citrullinated proteins are cleared from body and not encountered by immune system. However, in rheumatoid arthritis patients, these are not cleared. Anti-citrullinated protein antibodies are detectable in patients at risk of rheumatoid arthritis long before the onset of the disease. The concentration of which normally increases as the disease progress. Hence, these are important for diagnosis of rheumatoid arthritis. This review is focused on the importance of anti-citrullinated protein antibodies in disease pathogenesis and its importance in the diagnosis of rheumatoid arthritis.
25481551 Epigenetic changes: the missing link. 2014 Aug The association of rheumatoid arthritis (RA) with a number of genetic risk loci is well established; however, only part of the risk to develop the disease is based on genetics. Environmental factors significantly contribute to the pathogenesis. A gene-environment interaction for smoking and certain major histocompatibility complex (MHC) class II alleles has been shown to promote anti-citrullinated protein antibody (ACPA)-positive RA; however, the molecular mechanisms of interaction remain unclear. In contrast to the genetic background, epigenetic factors are responsive to external stimuli and can modulate gene expression. Therefore, epigenetic mechanisms may function as intermediaries between genetic risk alleles and environmental factors. In this review, epigenetic mechanisms are explained and the evidence for epigenetic changes relevant for the pathogenesis of RA and potential therapeutic applications are discussed.
23472042 Work participation and arthritis: a systematic overview of challenges, adaptations and opp 2013 Jul OBJECTIVE: Understanding the factors that play a role in maintaining people with inflammatory arthritis in the workforce may aid the design of interventions to support work participation. The objective of this systematic overview is to summarize qualitative studies that explore experiences of patients with inflammatory arthritis to remain employed or return to work. METHODS: Bibliographic databases including MEDLINE, EMBASE and PsycInfo were searched until December 2011 to identify any qualitative studies that focused on experiences, challenges or adaptations of patients with inflammatory arthritis to remain employed. Thematic analyses were used to identify any first or higher order themes for which all data were entered into MAXQDA software. In addition, methodological quality was assessed using an eight-item checklist. RESULTS: Of 6338 citations, 10 studies were included. RA was the condition in eight studies. Individual interviews (six studies) were used more frequently than group interviews (four studies). Methodological quality varied from 2 to 8 points and had no effect on the number of themes identified. Thematic analyses showed seven key concepts important to patients, including disease symptoms, management of the disease, socioeconomic issues, work conditions and adaptations, emotional challenges, interpersonal issues affecting work and family life and meaning of work. CONCLUSION: By including studies from different countries and settings, we show a comprehensive overview of themes considered important by patients and strengthen our belief that these factors should be considered in interventions that aim to improve work participation for patients with inflammatory arthritis.
23934221 Trajectories of functional limitation in early rheumatoid arthritis and their association 2013 Nov OBJECTIVE: This study aimed to identify subgroups with distinct trajectories of functional (HAQ) progression over 10 years following diagnosis of RA and identify baseline characteristics associated with the trajectories and their prognostic value for mortality. METHODS: Between 1986 and 1998, 1460 patients with RA symptoms <2 years and prior to disease-modifying treatment (DMARDs) were recruited to an inception cohort (Early RA Study). Standard clinical, functional and laboratory assessments were performed at presentation and annually. Deaths were tracked by the National Health Service Central Register. Growth mixture modelling was used to identify distinct trajectories of HAQ score progression and survival analysis employed to compare all-cause mortality across the trajectory classes. RESULTS: Four HAQ score progression classes were identified: moderate increasing (46%), low stable (6%), moderate stable (28%) and high stable (20%). Only the moderate-increasing class exhibited an accelerated decline in function over normal ageing. Compared with the moderate-increasing class, individuals with high-stable HAQ scores were more likely to be female, have more severe disease and other coexistent conditions. Low-stable class patients were more likely to be male and report less pain. The high-stable class had increased risk of mortality compared with the moderate-increasing class after adjusting for potential confounding factors, whereas low-stable and moderate-stable classes were at reduced mortality risk. CONCLUSION: The effect of RA on function is set within the first few years and is affected by comorbidity. Identifying distinct groups of patients may help to target those at greater risk of poor functional outcome and mortality.
25627299 [Demographic and clinical features of patients with rheumatoid arthritis in Piauí, Brazil 2014 Sep INTRODUCTION: Brazilian epidemiological studies on rheumatoid arthritis are scarce, mainly in the northeast; thus many data currently available originate from the international literature. OBJECTIVES: To describe demographic, clinical and serological characteristics of patients with rheumatoid arthritis (RA) followed-up by the same physician, in state of Piauí, Brazil. PATIENTS AND METHODS: Data were collected between August 2010 and March 2013, in three health services of Piauí that provided health care in Rheumatology: a university-affiliated hospital, a public outpatient clinic and a private clinic. RESULTS: The numbers represent mean ± SD or percentage: 47.5±11.03 years-old non-Caucasian woman, non-smoker (59.2%), low educational level, mean disease duration of 7.7 years ± 7.6, and major extra-articular manifestations were rheumatoid nodules (19.4%) and sicca syndrome (46.9%). CONCLUSION: Features of rheumatoid arthritis obtained in this study are similar to those found in some national and international studies, but we observed higher female preponderance and illiteracy rate, in addition to a moderately severe erosive disease on average, with frequent sicca and other extra-articular manifestations.
24390385 Temporal summation of pain and ultrasound Doppler activity as predictors of treatment resp 2014 Jan 3 INTRODUCTION: Chronic pain is common in rheumatoid arthritis (RA) and may still persist despite regression of objective signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may play a role in the generation of chronic pain in RA. Application of the disease activity score DAS28 can classify some patients with active RA solely based on a high tender joint count and poor patient global health score. In such cases, intensified treatment with anti-inflammatory drugs would be expected to yield poorer results than in cases with DAS28 elevation due to a high score for swollen joints and C reactive protein (CRP). Evaluation of central pain sensitisation in patients with few inflammatory indices may be a predictive tool regarding the effect of anti-inflammatory treatment. Computerised pneumatic cuff pressure algometry (CPA) is a method for assessing temporal summation (ie, degree of central sensitisation). The main objective of this study was to examine the prognostic values of pressure pain-induced temporal summation, ultrasound Doppler activity and the interaction between them in relation to treatment response (DAS28-CRP change) in patients with RA initiating any anti-inflammatory therapy. METHOD AND ANALYSIS: 120 participants ≥18 years of age will be recruited. Furthermore, they must be either (1) diagnosed with RA, untreated with disease-modifying antirheumatic drugs for at least 6 months and about to initiate disease-modifying antirheumatic drug treatment or (2) about to begin or switch treatment with any biological drug for their RA. Data (clinical, imaging, blood samples, patient reported outcomes and CPA measurements) will be collected from each participant at baseline and after 4 months of anti-inflammatory treatment. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee for the Copenhagen region (H-4-2013-007). Dissemination will occur through presentations and publication in international peer-reviewed journals.
24146764 Genetic control of spontaneous arthritis in a four-way advanced intercross line. 2013 Identifying the genetic basis of complex diseases, such as rheumatoid arthritis, remains a challenge that requires experimental models to reduce the genetic and environmental variability. Numerous loci for arthritis have been identified in induced animal models; however, few spontaneous models have been genetically studied. Therefore, we generated a four-way advanced intercross line (AIL) from four inbred strains, including BXD2/TyJ which spontaneously develops autoimmune arthritis. A genome-wide scan for spontaneous arthritis was performed in a cohort of 366 mice of the fourth generation (G4) of this cross. Five loci contributing to clinical phenotypes were identified in chromosomes 3, 7, 13, 18, and X. Three of the loci found in this study, confirm previously identified loci; whereas two of them are novel loci. Interesting candidate genes for the loci are highlighted. This study provides a genetic overview of spontaneous arthritis in mice and aids to solve the genetic etiology of rheumatoid arthritis and to gain a better understanding of the disease.
24782222 Subgrouping of patients with rheumatoid arthritis based on pain, fatigue, inflammation, an 2014 Aug OBJECTIVE: Among patients with rheumatoid arthritis (RA), pain may be attributed to peripheral inflammation or other causes, such as central pain mechanisms. The aim of this study was to use self-report measures and physical examination findings to identify clusters of RA patients who may have different causes of pain as well as different prognoses and treatment options. METHODS: Data from 169 RA patients with pain scores of >0 (on a 10-point numeric rating scale) in the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study were analyzed. The patients completed questionnaires on pain, fatigue, and psychosocial factors. A hierarchical agglomerative clustering procedure with Ward's method was used to obtain subgroups. Multivariate analysis of variance was used to determine the contribution of each variable in a cluster. General linear regression models were used to examine differences in clinical characteristics across subgroups. Discriminant analyses were performed to determine coefficients for linear combinations of variables that assigned cluster membership to individual cases. RESULTS: Three clusters best fit these data. Cluster 1 consisted of 89 individuals with low levels of inflammation, pain, fatigue, and psychosocial distress. Cluster 2 consisted of 57 individuals with minimal inflammation but high levels of pain, fatigue, and psychosocial distress. Cluster 3 consisted of 23 individuals with active inflammatory disease, manifested by high swollen joint counts, high C-reactive protein levels, and high levels of pain and fatigue. CONCLUSION: Although most patients had low levels of inflammation, pain, and fatigue, 47.3% continued to report having moderate to high levels of pain and fatigue. Most of these patients had minimal signs of inflammation but high levels of fatigue, pain catastrophizing, and sleep disturbance, indicative of a chronic widespread pain syndrome.
25402254 [Cost analysis of treatment for severe rheumatoid arthritis in a city in southern Brazil]. 2013 Nov Treatment of rheumatoid arthritis involves the use of medicines, non-pharmaceutical therapies, medical appointments, and complimentary tests, among other procedures. Based on sources of payment, this article presents the direct medical costs related to treatment of rheumatoid arthritis. The cost analysis included 103 patients with severe rheumatoid arthritis treated at the Specialized Division of Pharmaceutical Care in Florianopolis, Santa Catarina State, Brazil. Total annual direct cost was R$ 2,045,596.55 (approximately one million US dollars), or R$ 19,860.16 per patient/year (slightly less than ten thousand US dollars). Total cost breakdown was as follows: 90.8% for medicines, 2.5% for hospitalizations, 2.2% for complimentary tests, 2.1% for medical appointments, and 2.4% for all other costs. The public sector accounted for 73.6% of the total direct medical costs and 79.3% of the cost of medicines. The cost analysis provided a profile of how a group of individuals with a chronic non-communicable disease that requires resources circulates in the public-private mix that characterizes the Brazilian health system.
24143915 Work disability in Finnish patients with rheumatoid arthritis: a 15-year follow-up. 2014 Jan OBJECTIVES: To investigate long-term work disability of patients with early rheumatoid arthritis (RA) and to examine impact of early disease activity and radiological progression on the loss of final work capacity. METHODS: Work disability due to RA was studied over 15 years in 86 Finnish patients with early RA and available for the labour force at study entry. RA-related retirement was studied in relation to early disease activity defined as the 28-joint disease activity score area under curve (DAS28 AUC) during the first 12 months and the impact of early radiological progression from the baseline to year 1. RESULTS: The RA-related retirement rate was 7% after the first year, 11% after 2 years, 19% after 5 years, 33% after 10 years and 39% after 15 years. Of the patients with low disease activity (DAS28 AUC ≤3.2) none were retired during the first 3 years. The retirement rate was also lower in subsequent years (10% after 5 years, 14% after 10 years, and 27% after 15 years) among these patients compared to those with DAS28 AUC >3.2 (28%, 55%, and 64%, respectively). A similar trend was evident among patients with no radiological progression (≤1 unit increase in Larsen score) and those with >1 Larsen unit of progression during the first year of RA. CONCLUSIONS: Our study suggests that low disease activity and halting of radiological progression during the first year of the disease improve possibilities to maintain work capacity in RA during the subsequent 15 years.