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ID PMID Title PublicationDate abstract
28408110 Evaluation of the activity of rheumatoid arthritis in clinical practice. Agreement between 2017 Oct 11 INTRODUCTION AND OBJECTIVE: To achieve control of rheumatoid arthritis (RA) it is necessary to be able to evaluate its activity. The American College of Rheumatology (ACR) recommends for this purpose indexes of activity that can be performed by the patient (PAS-II and RAPID-3) and IA including medical evaluation with laboratory studies (DAS28 and SDAI) or without them (CDAI). The objective was to analyze the concordance between self-rated clinimetric evaluation and clinimetric evaluation performed by the physician. PATIENTS AND METHOD: Analytical cross-sectional study in 126 patients with RA. The agreement was evaluated through the weighted κ coefficient and the Krippendorff's α coefficient. RESULTS: The PAS-II and RAPID-3 significantly correlated with all variables included in the core set of measures recommended by the ACR/EULAR. The agreement between PAS-II and CDAI-SDAI was good (κ: 0.6, α: 0.61-0.62), and moderate with DAS28-ESR (κ: 0.53, α: 0.56). The concordance between RAPID-3 and CDAI-SDAI was moderate (κ: 0.55-0.57, α: 0.50-0.51), and moderate with DAS28-ESR (κ: 0.55, α: 0.53). When categorizing the activity in remission/low activity vs. moderate/severe activity, the agreement was greater with the PAS-II (0.59 vs. 0.34; P=.012). CONCLUSION: The good concordance between PAS-II and SDAI supports their use in clinical practice, especially if biomarkers of inflammation or the possibility of joint count are not available. However, in order to recommend its routine application in clinical practice, it is necessary to perform longitudinal studies that assess its responsiveness.
29220376 C5a and C5aR are elevated in joints of rheumatoid and psoriatic arthritis patients, and C5 2017 Complement activation correlates to rheumatoid arthritis disease activity, and increased amounts of the complement split product C5a is observed in synovial fluids from rheumatoid arthritis patients. Blockade of C5a or its receptor (C5aR) is efficacious in several arthritis models. The aim of this study was to investigate the role of C5a and C5aR in human rheumatoid arthritis and psoriatic arthritis-both with respect to expression and function. Synovial fluid, blood and synovial samples were obtained from rheumatoid arthritis, psoriatic arthritis and osteoarthritis patients as a less inflammatory arthritis type, and blood from healthy subjects. Cells infiltrating synovial tissue were analysed by immunohistochemistry and flow cytometry. SF and blood were analysed for biomarkers by flow cytometry or ELISA. The effect of a blocking anti-human C5aR mAb on leukocyte migration was determined using a Boyden chamber. Appropriate statistical tests were applied for comparisons. C5aR+ cells were detected in most rheumatoid arthritis, in all psoriatic arthritis, but not in non-inflammatory control synovia. C5aR+ cells were primarily neutrophils and macrophages. C5aR+ macrophages were mainly found in lymphoid aggregates in close contact with T cells. C5a levels were increased in both rheumatoid arthritis and psoriatic arthritis synovial fluid compared to osteoarthritis, and in blood from rheumatoid arthritis compared to healthy subjects. Neutrophil and monocyte migration to rheumatoid arthritis synovial fluid was significantly inhibited by anti-C5aR. The data support that the C5a-C5aR axis may be driving the infiltration of inflammatory cells into the synovial fluid and synovium in both rheumatoid and psoriatic arthritis, and suggest that C5a or C5aR may be a promising treatment target in both diseases.
28299396 No correlation between MTHFR c.677 C > T, MTHFR c.1298 A > C, and ABCB1 c.3435 C†2017 Jun CONTEXT: The c.677 C > T and c.1298 A > C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene and c.3435 C > T polymorphism of ATP-Binding cassette B1 (ABCB1) gene are reported as pharmacogenetic markers, influencing the methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA) patients. OBJECTIVES: The aims of this study were to determine the relationship between these polymorphisms and clinical response and/or adverse drug reaction (ADRs) to MTX treatment. MATERIALS AND METHODS: The cohort of our study was composed of 110 RA patients of the West Algerian population. The clinical response was evaluated using the disease activity score 28 (DAS28) and the ADRs were collected after physical examination of patients. All samples were genotyped for theses polymorphisms by TaqMan(®) allelic discrimination assay. RESULTS: Based on EULAR criteria, 59.09% RA patients were responders and ADRs were observed in 40.9% patients. The frequency distribution of these three polymorphisms was similar between the responders and the non-responders. The same result was found on ADRs study and no significant difference of distribution between the presence of ADRs group and absence of ADRs group was observed. DISCUSSION: Our study joins the results that found in others population in the world. CONCLUSION: We have demonstrated, for the first time in the West Algerian population, that these polymorphisms were not predictive for clinical response and/or ADRs to MTX therapeutic outcome.
27878579 G protein coupled receptors signaling pathways implicate in inflammatory and immune respon 2017 May INTRODUCTION: G protein-coupled receptors (GPCRs) are transmembrane receptor proteins, which allow the transfer of signals across the membrane. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response. GPCRs signaling pathways play a significant role in inflammatory and immune response processes including RA. FINDINGS: In this review, we have focused on the advances in GPCRs signaling pathway implicating the inflammatory and immune response of RA. The signaling pathways of GPCRs-adenylyl cyclase (AC)-cyclic adenosine 3', 5'-monophosphate (cAMP) include β(2) adrenergic receptors (β(2)-ARs)-AC-cAMP signaling pathways, E-prostanoid2/4 (EP2/4)-AC-cAMP signaling pathways and so on. Regulatory proteins, such as G protein-coupled receptor kinases (GRKs) and β-arrestins, play important modulatory roles in GPCRs signaling pathway. GPCRs signaling pathway and regulatory proteins implicate the pathogenesis process of inflammatory and immune response. CONCLUSION: GPCRs-AC-cAMP signal pathways involve in the inflammatory and immune response of RA. Different signaling pathways are mediated by different receptors, such as β(2)-AR, PGE2 receptor, chemokines receptor, and adenosine receptor. GRKs and β-arrestins are crucial proteins in the regulation of GPCRs signaling pathways. The potential therapeutic targets as well as strategies to modulate GPCRs signaling pathway are new development trends.
28186160 3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiati 2017 Feb 10 Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis. Here we demonstrated that 3-bromopyruvate (BrPA), a specific HK2 inhibitor, significantly decreased the arthritis scores and the histological scores in SKG mice, with a significant increase in Treg cells, decrease in Th17 cells, and decrease in activated DCs in the spleen. In vitro, BrPA facilitated the differentiation of Treg cells, suppressed Th17 cells, and inhibited the activation of DCs. These results suggested that BrPA may be a therapeutic target of murine arthritis. Although the role of IL-17 is not clarified in the treatment of RA, targeting cell metabolism to alter the immune cell functions might lead to a new therapeutic strategy for RA.
28653215 NLRP1, PTPN22 and PADI4 gene polymorphisms and rheumatoid arthritis in ACPA-positive Singa 2017 Aug Studies have shown that the genetic risk factors for rheumatoid arthritis (RA) differ substantially between Asian and Caucasian populations. Even among Asian populations, the genetic contributions of NLRP1, PTPN22 and PADI4 have been controversial. Consequently, we sought to address these separate findings and determine whether any of these proposed risk variants are associated with RA susceptibility, onset, DAS activity and erosion in a Singaporean Chinese cohort. We genotyped five SNPs within NLRP1 (rs878329 and rs6502867), PTPN22 (rs2488457 and rs6665194), and PADI4 (rs2240340) in 500 anti-cyclic citrullinated peptide antibody-positive (ACPA) patients with RA and 500 healthy controls using TaqMan assays. The CC genotype of NLRP1 rs878329 and TT genotype of PADI4 rs2240340 were associated with RA susceptibility. The risk association of the T allele of PADI4 rs2240340 with RA was confirmed through a meta-analysis based on previous reports in Asian populations. The GG genotype of PTPN22 rs6665194 (-3508A>G) was associated with significantly reduced risk of RA. No significant association was found for NLRP1 rs6502867 T/C and PTPN22 rs2488457 G/C polymorphisms. None of the five SNPs was associated with RA's clinical features. This work supports the association of the T allele of PADI4 rs2240340 with RA in Asians. The roles of NLRP1 rs878329 G/C and PTPN22 rs6665194 A/G polymorphisms were demonstrated for the first time. We also propose rs6665194 to be a promising candidate for RA risk evaluation between ethnicities.
28500376 The PTPN22 R263Q polymorphism confers protection against systemic lupus erythematosus and 2017 Sep OBJECTIVE: The functional PTPN22 R620W polymorphism (rs2476601) is clearly associated with susceptibility to several autoimmune diseases (ADs). However, the PTPN22 R263Q polymorphism (rs33996649) has been scarcely explored in different ADs. Here we aimed to examine the associations of the PTPN22 R620W and R263Q polymorphisms with susceptibility to or protection against rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves' disease (GD) among Mexican patients. METHODS: We conducted a case-control study including 876 patients (405 with SLE, 388 with RA, and 83 with GD) and 336 healthy control individuals. PTPN22 genotypes were determined using the TaqMan 5' allele discrimination assay. RESULTS: PTPN22 R620W was associated with GD susceptibility (OR 4.3, p = 0.004), but was not associated with SLE (OR 1.8, p = 0.19). We previously demonstrated that this polymorphism is associated with RA susceptibility (OR 4.17, p = 0.00036). Moreover, PTPN22 R263Q was associated with protection against SLE (OR 0.09, p = 004) and RA (OR 0.28, p = 0.045), but was not associated with GD. CONCLUSIONS: Our data provide the first demonstration that PTPN22 R620W confers GD susceptibility among Latin-American patients. Moreover, this is the second report documenting the association of PTPN22 R263Q with protection against SLE and RA.
28852832 Down-titration of biologics for the treatment of rheumatoid arthritis: a systematic litera 2017 Nov Biologic therapies have improved the management of rheumatoid arthritis (RA) and the treat-to-target approach has resulted in many patients achieving remission. In the current treatment landscape, clinicians have begun considering dose reduction/tapering for their patients. Rheumatology guidelines in Asia, Europe, and the United States include down-titration of biologics but admit that the level of evidence is moderate. We conducted a systematic literature review to assess the published studies that evaluate down-titration of biologics in RA. The published literature was searched for studies that down-titrated the following biologics: abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Eligible studies included randomized controlled trials (RCTs), non-RCTs, observational, and pharmacoeconomic studies. The outcomes of interest were (1) efficacy and health-related quality of life, (2) disease flares, and (3) impact on cost. Eleven full-text publications were identified; only three were RCTs. Study results suggest that dosing down may be an option in many patients who have achieved remission or low disease activity. However, some patients are likely to experience a disease flare. Across the studies, the definition of disease flare and the down-titration criteria were inconsistent, making it difficult to conclude which patients may be appropriate and when to attempt down-titration. Studies have evaluated the practice of dosing down biologic therapy in patients with RA; however, a relatively small number of RCTs have been published. Although down-titration may be an option for some patients in LDA or remission, additional RCTs are needed to provide guidance on this practice.
28337536 Functional and patient-reported outcomes of the Swanson metacarpo-phalangeal arthroplasty 2017 May INTRODUCTION: Replacement of the metacarpo-phalangeal joints (MCPJ) with silastic Swanson's implants can help decrease pain, stiffness and allow for improved function in rheumatoid arthritis (RA). There is a lack of patient reported outcome measure (PROM) studies assessing the efficacy of this procedure in RA. The aim of this study was to report any change in function, pain, stiffness and satisfaction following the Swanson MCPJ replacement using patient reported outcomes in a rheumatoid population. METHODS: The combined results of 64 RA patients (71 hands) with 284 Swanson MCPJ arthroplasties (mean follow-up: 75.85 months) were assessed using the validated M-SACRAH questionnaire and a separate satisfaction questionnaire. Radiographic evaluation was performed to insure correct alignment of the hinged prosthesis postoperatively. No attempt was made to identify other predictors, radiologically or clinically. Data analysed in the study was interpreted in the context of the number of hands and survivorship was defined as implant fracture, loosening or revision. RESULTS: The mean total functional outcome score improved by 46.2% and the total pain outcome improved by 60.2%. The total stiffness outcome improved by 56.9% postoperatively and the results obtained from the satisfaction questions revealed that 73.2% of patients would retrospectively elect to have the procedure again. We report two postoperative complications in this group of superficial wound infections. Radiographically, all MCPJs showed improved alignment, however five patients reported worsening pain, four patients reported increased stiffness and four reported reduced function postoperatively. There was one re-operation of a 5th MCPJ Swanson's, which did not require implant exchange and one implant was revised. Implant survivorship was 98.6%. CONCLUSIONS: Patient satisfaction and functional surrogate markers were overall favourable. Our results support the continued use of Swanson silastic arthoplasty in advanced RA.
29303709 Cost-effectiveness of early treatment of ACPA-positive rheumatoid arthritis patients with 2018 May OBJECTIVES: Studies have reported that the presence of elevated anti-citrullinated protein antibodies (ACPA)/RF levels, together with joint erosions, is associated with higher disease burden in terms of disability and mortality in rheumatoid arthritis (RA). Abatacept has been shown to be effective in this patient population with favourable comparative data against adalimumab. However, few studies have investigated the cost-effectiveness of abatacept in this population to similar treatments such as TNFs. The objective of the study was to compare the cost-effectiveness of abatacept to adalimumab as a first bDMARD in ACPA-positive RA patients who failed treatment with methotrexate (MTX) in Germany. METHODS: A decision tree model was used to estimate the cost-effectiveness, from a payer's perspective, of different treatment sequences in RA over a two year time frame. The effectiveness criteria were defined as achieving the treatment target measured by the Disease Activity Score 28 (DAS28(CRP)<2.6; "remission"). A treatment switch to a different biologic as 2nd line and 3rd line bDMARD was allowed - in case of not achieving remission with therapy - every 6 months over a two year time period. Effectiveness data was based on randomised controlled trials (RCT) identified by an updated previous systematic literature search by the Institute for Quality and Efficiency in Health Care (IQWiG). Costs of medication and other direct medical costs were considered. Cost-effectiveness of RA treatment was investigated in ACPA-positive patients and presented as overall costs per day in remission. RESULTS: For ACPA-positive patients, treatment strategies including early treatment with abatacept had lower total costs per clinical outcome compared to later use. Treatment sequences starting with abatacept resulted in lower costs per day in remission (mean 330 €/day, range 328-333 €/day) compared to sequences starting with adalimumab (mean 384 €/day, range 378-390 €/day). Choice of the second or third biologic in the treatment sequences appears to have little impact on the costs per outcome. CONCLUSIONS: The results of this analysis suggest that in ACPA-positive RA patients treatment with abatacept appears to have lower costs per response (remission) compared to treatment with adalimumab as a first bDMARD.
28957552 Enrichment of malondialdehyde-acetaldehyde antibody in the rheumatoid arthritis joint. 2017 Oct 1 OBJECTIVE: To characterize the expression of malondialdehdye-acetaldehyde (MAA) adducts and anti-MAA antibody in articular tissues and serum of patients with RA. METHODS: Paired sera and SF were examined from 29 RA and 13 OA patients. Anti-MAA antibody, RF, ACPA and total immunoglobulin were quantified. SF-serum measures were compared within and between disease groups. The presence and co-localization of MAA, citrulline and select leukocyte antigens in RA and OA synovial tissues were examined using immunohistochemistry. RESULTS: Circulating and SF anti-MAA antibody concentrations were higher in RA vs OA by 1.5- to 5-fold. IgG (P < 0.001), IgM (P = 0.006) and IgA (P = 0.036) anti-MAA antibodies were higher in paired RA SF than serum, differences not observed for total immunoglobulin, RF or ACPA. In RA synovial tissues, co-localization of MAA with citrulline and CD19+ or CD27+ B cells was demonstrated and was much higher in magnitude than MAA or citrulline co-localization with T cells, monocytes, macrophages or dendritic cells (P < 0.01). CONCLUSION: Anti-MAA antibodies are present in higher concentrations in the RA joint compared with sera, a finding not observed for other disease-related autoantibodies. Co-localization of MAA and citrulline with mature B cells, coupled with the local enrichment of anti-MAA immune responses, implicates MAA-adduct formation in local autoantibody production.
28365576 Decreased Cardiovascular Mortality in Patients with Incident Rheumatoid Arthritis (RA) in 2017 Jun OBJECTIVE: To assess trends in cardiovascular (CV) mortality in patients with incident rheumatoid arthritis (RA) in 2000-07 versus the previous decades, compared with non-RA subjects. METHODS: The study population consisted of Olmsted County, Minnesota, USA residents with incident RA (age ≥ 18 yrs, 1987 American College of Rheumatology criteria was met in 1980-2007) and non-RA subjects from the same underlying population with similar age, sex, and calendar year of index. All subjects were followed until death, migration, or December 31, 2014. Followup was truncated for comparability. Aalen-Johansen methods were used to estimate CV mortality rates, adjusting for competing risk of other causes. Cox proportional hazards models were used to compare CV mortality by decade. RESULTS: The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 yrs; 68% women for both groups). Patients with incident RA in 2000-07 had markedly lower 10-year overall CV mortality (2.7%, 95% CI 0.6-4.9%) and coronary heart disease (CHD) mortality (1.1%, 95% CI 0.0-2.7%) than patients diagnosed in 1990-99 (7.1%, 95% CI 3.9-10.1% and 4.5%, 95% CI 1.9-7.1%, respectively; HR for overall CV death: 0.43, 95% CI 0.19-0.94; CHD death: HR 0.21, 95% CI 0.05-0.95). This improvement in CV mortality persisted after accounting for CV risk factors. Ten-year overall CV mortality and CHD mortality in 2000-07 RA incidence cohort was similar to non-RA subjects (p = 0.95 and p = 0.79, respectively). CONCLUSION: Our findings suggest significantly improved overall CV mortality, particularly CHD mortality, in patients with RA in recent years. Further studies are needed to examine the reasons for this improvement.
29291895 Evidence of reduced parasympathetic autonomic regulation in inflammatory joint disease: A 2018 Aug BACKGROUND: Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are inflammatory joint disorders (IJD) with increased risk of cardiovascular disease (CVD). Autonomic dysfunction (AD) is a risk factor for CVD, and parasympathetic AD is linked to key features of IJD such as inflammation, physical inactivity and pain. Heart-rate variability (HRV) is a marker of cardiac AD. The study objective was to compare parasympathetic cardiac AD, measured by HRV, between patients with IJD and healthy controls, using meta-analysis methodology, and to examine the impact of inflammation, physical inactivity and pain on HRV in IJD. METHODS: Medline, Embase and Amed were searched. Inclusion criteria were adult case-control studies published in English or a Scandinavian language, presenting HRV data in IJD. Two measures of HRV and 3 from the Ewing protocol were selected: square root of mean squared difference of successive R-R intervals (RMSSD), high frequency (HF), Ewing protocol; standing (E-S), breathing (E-B) and Valsalva (E-V). Patients with RA, SpA and healthy controls were compared separately using random-effects meta-analyses of standardized mean differences (SMD). RESULTS: In all, 35 papers were eligible for inclusion. For RMSSD the pooled SMD (95% CI) RA vs. controls was -0.90 (-1.35 to -0.44), for SpA vs. controls; -0.34 (-0.73 to 0.06). For HF pooled SMD RA vs. controls was -0.78 (-0.99 to -0.57), for SpA vs. controls; -0.04 (-0.22 to 0.13). All Ewing parameters were significantly lower in cases, except for E-V which was comparable between cases and controls in patients with RA. CONCLUSION: Patients with IJD have cardiac parasympathetic AD which is related to inflammation.
27789276 Tear Fluid Protein Changes in Dry Eye Syndrome Associated with Rheumatoid Arthritis: A Pro 2017 Jan PURPOSE: Sjögren syndrome (SS) secondary to rheumatoid arthritis (RA) affects lacrimal and salivary glands, and therefore dry eye syndrome (DES) is more prevalent in patients with RA. This study used a proteomic approach to identify potential biomarkers in tear of DES secondary to RA (DES-RA). METHODS: Tear specimens were collected with Schirmer strips from patients with DES with RA, patients with other types of dry eye (namely, primary Sjögrens and non-Sjögrens [NSS]), and age-matched controls. Tear proteins were subjected to 2D-differential gel electrophoresis (2D-DIGE), and the differentially expressed proteins were identified using nano ESI-LC-MS/MS analysis. RESULTS: Among the differentially regulated proteins of DES-RA that were identified, lactotransferrin isoform 1 precursor was found to be d own-regulated in 100% cases and SHC transforming 1 isoform in 63% of the cases, while proteins such as ribonuclease p protein subunit 20, protocadherin, and heterogeneous nuclear ribonucleoprotein Q isoform 6 were down-regulated in over 80% of the cases. Proteins such as Ecto-ADP ribosyltransferase 5 precursor, Rho-related GTP-binding protein, and RhoJ precursor were up-regulated in 80% of the cases. CONCLUSION: Functional annotation revealed that these proteins have roles in regulation, antimicrobial activity, immune, metabolic, and cellular processes. The study observed characteristic marker proteins differentially expressed in DES-RA that are previously unreported. Further validation is needed.
29442025 Sinomenine inhibits the inflammatory responses of human fibroblast-like synoviocytes via t 2017 Jun 1 Rheumatoid arthritis (RA) is a systemic autoimmune disorder mainly characterized by inflammation of the synovial tissue that can lead to destruction of bone and cartilage. Sinomenine is an alkaloid extracted from the stem of the Chinese medicinal plant Sinomenium acutum. It has been reported that sinomenine has immunosuppressive and anti-inflammatory properties. However, the molecular mechanism underlying the effect of sinominine on IL-1β-induced human RA fibroblast-like synoviocytes (RAFLS) is poorly understood. Therefore, in this study, we investigated the effect of sinomenine on the expression of inflammatory cytokines in IL-1β-treated human RAFLS in vitro and the underlying mechanism. RAFLS viability was evaluated using the MTS assay after sinomenine treatment. The levels of inflammatory cytokines were measured with ELISA, RT-PCR and western blot, respectively. The levels of TLR4 and its downstream signaling targets were determined by western blot analysis. We found that sinomenine suppressed not only NO and PGE2 production but also iNOS and COX-2 expression in IL-1β-induced RAFLS. It also inhibited the expression of TNF-α and IL-6 in IL-1β-stimulated RAFLS. Furthermore, sinomenine prevented IL-1β-induced TLR4, MyD88 and p-NF-κB p65 expression. Taken together, these results demonstrated that sinomenine prevented IL-1β-induced inflammation in human RAFLS at least in part by inhibiting the TLR4/MyD88/NF-κB signaling pathway, suggesting that sinomenine could be a potential agent in the treatment of RA.
28065486 Biologic Disease-modifying antirheumatic drug attributes in the first lines of treatment o 2018 Mar OBJECTIVE: To date, between 17% and 35% of patients with rheumatoid arthritis (RA) do not respond as expected to the initial biological therapy. The objective of this project is to recognize and weigh the attributes of biologic DMARD (bDMARD) to identify the most appropriate for each case, in the first lines of treatment of RA (after inadequate response to at least one synthetic DMARD or previous bDMARD). METHODS: To recognize the possible attributes that could define the bDMARD, we performed a systematic search of the literature that recognized the possible attributes involving general aspects, pharmacology, efficacy, safety, management, and cost. Then a Delphi process was conducted with two rounds among a group of selected expert rheumatologists in the management of RA indicating the degree of agreement with the attributes identified in the literature. The project was completed between February and September 2015, indicating the degree of importance that was ascribed to each attribute. Two criteria were applied to determine the consistency of results: 1) based on the median and interquartile range; and 2) on the simultaneous compliance with mean, median, standard deviation, interquartile range and coefficient of variation. The agreement and final ratification of the expert panel were also determined. RESULTS: Eighty-three Spanish rheumatologists participated and completed both rounds of the Delphi process. In no case was the importance of the 77 attributes identified considered to be low; 75 of 77 (97.4%) were considered highly important and 76 of 77 (98.7%) were ratified. Fifteen attributes had the support of 100% of the working group. CONCLUSIONS: There was a high degree of agreement concerning the selected attributes. Fifteen of them had the support of 100% of the working group and could be considered the definition of the ideal bDMARD in the first lines of RA treatment.
28786274 [SUSTAINABILITY OF RITUXIMAB IN CONCOMMITANT TREATMENT WITH METHOTREXATE OR LEFLUNOMIDE IN 2017 Jul INTRODUCTION: Rituximab is a biologic agent approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate (MTX) or leflunomide (LEF). However, limited data in the literature suggests that rituximab may have the same efficacy profile whether used in combination with MTX or as monotherapy. The aim of our study is to compare the sustainability of rituximab as monotherapy to combined therapy with MTX or LEF in Israeli patients with RA. METHODS: A total of 35 RA patients treated with rituximab combined with MTX or LEF were compared with 26 RA patients treated with rituximab monotherapy regarding sustainability of rituximab treatment and its relationship to some patient and disease-related factors. RESULTS: There was no difference in patient-related and disease-related parameters between patients treated with rituximab as monotherapy or combined with MTX/LEF. The survival of rituximab was similar in both groups (88.5% in the monotherapy group and 82.6% in the combined therapy group, p=NS), with similar percentages of patients discontinuing this biologic agent, whether due to inefficacy or side effects. CONCLUSIONS: Rituximab may be considered as a biologic monotherapy in RA patients. Further prospective studies, evaluating sustainability of rituximab as a monotherapy in patients with RA are warranted.
28781131 Muscle Weakness in Rheumatoid Arthritis: The Role of Ca(2+) and Free Radical Signaling. 2017 Sep In addition to the primary symptoms arising from inflammatory processes in the joints, muscle weakness is commonly reported by patients with rheumatoid arthritis (RA). Muscle weakness not only reduces the quality of life for the affected patients, but also dramatically increases the burden on society since patients' work ability decreases. A 25-70% reduction in muscular strength has been observed in pateints with RA when compared with age-matched healthy controls. The reduction in muscle strength is often larger than what could be explained by the reduction in muscle size in patients with RA, which indicates that intracellular (intrinsic) muscle dysfunction plays an important role in the underlying mechanism of muscle weakness associated with RA. In this review, we highlight the present understanding of RA-associated muscle weakness with special focus on how enhanced Ca(2+) release from the ryanodine receptor and free radicals (reactive oxygen/nitrogen species) contributes to muscle weakness, and recent developments of novel therapeutic interventions.
28320445 Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arth 2017 Mar 20 BACKGROUND: During pregnancy, patients with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) can experience active disease, which might be influenced by adjustment of treatment around conception. The aim of this study was to identify possible risk factors of disease flares during pregnancy and to evaluate the effect of treatment in pregnant patients experiencing a flare. METHODS: Pregnant patients with RA and axSpA were prospectively followed before, during, and after pregnancy. Disease activity and flares of disease activity were analyzed in regard to medication. RESULTS: Among 136 pregnant patients, disease flares during pregnancy occurred in 29% of patients with RA and in 25% of patients with axSpA. In both diseases, active disease and tumor necrosis factor inhibitor (TNFi) discontinuation in early pregnancy were identified as risk factors for disease flares during pregnancy. Of 75 patients with RA, 15 patients were on TNFi and discontinued the treatment at the time of the positive pregnancy test. After stopping TNFi, disease activity increased, which was reflected by peaking C-reactive protein levels at the first trimester. The relative risk of flare in patients with RA stopping TNFi was 3.33 (95% CI 1.8-6.1). Initiation of TNFi or glucocorticosteroid (GC) treatment in 60% of these patients resulted in disease improvement at the second and third trimesters. In comparison, patients with RA without TNFi in the preconception period, most of whom had used pregnancy-compatible antirheumatic drugs, showed mild and stable disease activity before and during pregnancy. Of 61 patients with axSpA, 24 patients were on TNFi and discontinued the treatment at the time of the positive pregnancy test. In patients with axSpA stopping TNFi, a disease aggravation at the second trimester could be observed. The relative risk of flare in this group was 3.08 (95% CI 1.2-7.9). In spite of initiated TNFi or GC treatment in 62.5% of these patients, disease activity remained elevated throughout pregnancy. Patients with axSpA without TNFi in the preconception period showed persistent high disease activity from prepregnancy until the postpartum period. CONCLUSIONS: On the basis of a risk-benefit analysis, to stabilize disease activity and to prevent a flare during pregnancy in patients with RA and axSpA, tailored medication including TNF inhibitors should be considered beyond conception.
29101015 DNA damage, metabolism and aging in pro-inflammatory T cells: Rheumatoid arthritis as a mo 2018 May The aging process is the major driver of morbidity and mortality, steeply increasing the risk to succumb to cancer, cardiovascular disease, infection and neurodegeneration. Inflammation is a common denominator in age-related pathologies, identifying the immune system as a gatekeeper in aging overall. Among immune cells, T cells are long-lived and exposed to intense replication pressure, making them sensitive to aging-related abnormalities. In successful T cell aging, numbers of naïve cells, repertoire diversity and activation thresholds are preserved as long as possible; in maladaptive T cell aging, protective T cell functions decline and pro-inflammatory effector cells are enriched. Here, we review in the model system of rheumatoid arthritis (RA) how maladaptive T cell aging renders the host susceptible to chronic, tissue-damaging inflammation. In T cells from RA patients, known to be about 20years pre-aged, three interconnected functional domains are altered: DNA damage repair, metabolic activity generating energy and biosynthetic precursor molecules, and shaping of plasma membranes to promote T cell motility. In each of these domains, key molecules and pathways have now been identified, including the glycolytic enzymes PFKFB3 and G6PD; the DNA repair molecules ATM, DNA-PKcs and MRE11A; and the podosome marker protein TKS5. Some of these molecules may help in defining targetable pathways to slow the T cell aging process.