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ID PMID Title PublicationDate abstract
27107307 Foot orthoses in the management of chronic subtalar and talo crural joint pain in rheumato 2016 Jun BACKGROUND: This pilot study investigated whether semi-rigid and soft orthoses had an effect on pain, disability and functional limitation in participants with chronic rheumatoid hindfoot involvement. METHODS: Participants with chronic hindfoot pain were randomly assigned to 2 groups, commencing either with semi-rigid Subortholene orthoses or soft EVA orthoses. The Foot Function Index and the Ritchie Articular Index were administered pre- and post-intervention, which lasted for 3 months. Following a 2 week washout period, each group was switched over to the other type of orthoses. RESULTS: Nine female participants (mean age 52.2years (SD 9.1); mean weight 71kg (SD 12.64); mean height 160cm (SD 5.18)) with a mean RA duration of 11.7years (SD 7.83), and a mean ankle/subtalar joint pain duration of 5.7years (SD 2.62), completed the programme. Mean improvement in FFI score for both orthoses resulted in the same statistical significance (p=0.001). Statistically significant reduction in pain, disability and functional limitation was observed for both interventions, together with improvement in the Ritchie Articular Index score. CONCLUSION: Both Subortholene and EVA orthoses significantly reduced pain, disability and functional limitations in participants with chronic ankle/subtalar joint pain in rheumatoid arthritis.
25602291 Adherence to biologic therapies and associated factors in rheumatoid arthritis, spondyloar 2015 Jul OBJECTIVES: To analyse the evidence on adherence to biologic therapies in rheumatoid arthris (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). METHODS: Systematic review of studies retrieved by a sensitive search strategy in MEDLINE database (1961 through March 2012). To be selected, studies had to include patients with RA, SpA, or PsA, treatment with intravenous or subcutaneous biologic therapies, and had to report on measures of adherence. By design, only randomised controlled trials (RCT) or high quality cohort studies with a control group were selected. RESULTS: A total of 24 studies were included, of which 12 reported results from national or local biologic registers, 9 were retrospective studies, 2 prospective studies, and only one was an RCT. Patients included were mostly women with diagnosis of RA or SpA and, less frequently, PsA. There was a great variability in the definition of adherence, measurement methods, and associated factors analysed. In general, adherence to etanercept was superior to that of other biologics, by the measures utilised. The main predictive factors - age, sex, comorbidity, baseline clinical condition, previous or concomitant use of DMARDs, anti-TNF in monotherapy or in combination with MTX - produced diverse, even divergent results across studies. CONCLUSIONS: There is a wide variability related to the adherence concept and its measurement, reflecting the complexity of the phenomenon. In order to draw more consistent conclusions about the relative value of predictive factors on adherence and persistence of biological therapy, larger controlled studies with better selection of variables and analysis of interactions are needed.
26181632 Antiinflammatory Activity of a Novel Folic Acid Targeted Conjugate of the mTOR Inhibitor E 2015 Jul 8 Folate receptor (FR)-β has been identified as a promising target for antimacrophage and antiinflammatory therapies. In the present study, we investigated EC0565, a folic acid-derivative of everolimus, as a FR-specific inhibitor of the mammalian target of rapamycin (mTOR). Because of its amphiphilic nature, EC0565 was first evaluated for water solubility, critical micelle formation, stability in culture and FR-binding specificity. Using FR-expressing macrophages, the effect of EC0565 on mTOR signaling and cellular proliferation was studied. The pharmacokinetics, metabolism and bioavailability of EC0565 were studied in normal rats. The in vivo activity of EC0565 was assessed in rats with adjuvant arthritis, a "macrophage-rich" model with close resemblance to rheumatoid arthritis. EC0565 forms micellar aggregates in physiological buffers and demonstrates good water solubility as well as strong multivalent FR-binding capacity. EC0565 inhibited mTOR signaling in rat macrophages at nanomolar concentrations and induced G0/G1 cell cycle arrest in serum-starved RAW264.7 cells. Subcutaneously administered EC0565 in rats displayed good bioavailability and a relatively long half-life (~12 h). When given at 250 nmol/kg, EC0565 selectively inhibited proliferating cell nuclear antigen expression in thioglycollate-stimulated rat peritoneal cells. With limited dosing regimens, the antiarthritic activity of EC0565 was found superior to that of etanercept, everolimus and a nontargeted everolimus analog. The in vivo activity of EC0565 was also comparable to that of a folate-targeted aminopterin. Folate-targeted mTOR inhibition may be an effective way of suppressing activated macrophages in sites of inflammation, especially in nutrient-deprived conditions, such as in the arthritic joints. Further investigation and improvement upon the physical and biochemical properties of EC0565 are warranted.
27726376 Immunogenic HLA-DR-Presented Self-Peptides Identified Directly from Clinical Samples of Sy 2017 Jan 6 Human leukocyte antigen-antigen D related (HLA-DR) molecules are highly expressed in synovial tissue (ST), the target of the immune response in chronic inflammatory forms of arthritis. Here, we used LC-MS/MS to identify HLA-DR-presented self-peptides in cells taken directly from clinical samples: ST, synovial fluid mononuclear cells (SFMC), or peripheral blood mononuclear cells (PBMC) from five patients with rheumatoid arthritis (RA) and eight with Lyme arthritis (LA). We identified 1593 non-redundant HLA-DR-presented peptides, derived from 870 source proteins. A total of 67% of the peptides identified in SFMC and 55% of those found in PBMC were found in ST, but analysis of SFMC/PBMC also revealed new antigen-presented peptides. Peptides were synthesized and examined for reactivity with the patients' PBMC. To date, three autoantigens in RA and four novel autoantigens in LA, presented in ST and/or PBMC, were shown to be targets of T- and B-cell responses in these diseases; ongoing analyses may add to this list. Thus, immunoprecipitation and LC-MS/MS can now identify hundreds of HLA-DR-presented self-peptides from individual patients' tissues or fluids with mixed cell populations. Importantly, identification of HLA-DR-presented peptides from SFMC or PBMC allows testing of more patients, including those early in the disease. Direct analysis of clinical samples facilitates identification of novel immunogenic T-cell epitopes.
26301417 Methods to Develop an Electronic Medical Record Phenotype Algorithm to Compare the Risk of 2015 BACKGROUND: Typically, algorithms to classify phenotypes using electronic medical record (EMR) data were developed to perform well in a specific patient population. There is increasing interest in analyses which can allow study of a specific outcome across different diseases. Such a study in the EMR would require an algorithm that can be applied across different patient populations. Our objectives were: (1) to develop an algorithm that would enable the study of coronary artery disease (CAD) across diverse patient populations; (2) to study the impact of adding narrative data extracted using natural language processing (NLP) in the algorithm. Additionally, we demonstrate how to implement CAD algorithm to compare risk across 3 chronic diseases in a preliminary study. METHODS AND RESULTS: We studied 3 established EMR based patient cohorts: diabetes mellitus (DM, n = 65,099), inflammatory bowel disease (IBD, n = 10,974), and rheumatoid arthritis (RA, n = 4,453) from two large academic centers. We developed a CAD algorithm using NLP in addition to structured data (e.g. ICD9 codes) in the RA cohort and validated it in the DM and IBD cohorts. The CAD algorithm using NLP in addition to structured data achieved specificity >95% with a positive predictive value (PPV) 90% in the training (RA) and validation sets (IBD and DM). The addition of NLP data improved the sensitivity for all cohorts, classifying an additional 17% of CAD subjects in IBD and 10% in DM while maintaining PPV of 90%. The algorithm classified 16,488 DM (26.1%), 457 IBD (4.2%), and 245 RA (5.0%) with CAD. In a cross-sectional analysis, CAD risk was 63% lower in RA and 68% lower in IBD compared to DM (p<0.0001) after adjusting for traditional cardiovascular risk factors. CONCLUSIONS: We developed and validated a CAD algorithm that performed well across diverse patient populations. The addition of NLP into the CAD algorithm improved the sensitivity of the algorithm, particularly in cohorts where the prevalence of CAD was low. Preliminary data suggest that CAD risk was significantly lower in RA and IBD compared to DM.
24842476 Early response to certolizumab pegol predicts long-term outcomes in patients with active r 2015 Jan OBJECTIVES: A post-hoc analysis was performed to determine the relationship between the timing and magnitude of DAS28(ESR) response and long term outcomes in Japanese patients after 1 year of CZP treatment. METHODS: Our analysis included 82 J-RAPID trial patients treated with CZP 200 mg and methotrexate, and 116 HIKARI trial patients treated with CZP 200 mg alone or with disease-modifying agents other than methotrexate. Remission rates and changes in mTSS at year 1 were compared to the DAS28(ESR) response at week 12 of CZP treatment. RESULTS: After 1 year of treatment, remission was achieved in 41.3% of the J-RAPID and 34.9% of the HIKARI patients with a week 12 DAS28(ESR) response of ≥ 1.2. In comparison, patients with a DAS28(ESR) response of < 1.2 at week 12 only had a < 7% probability of achieving remission and displayed higher change in mTSS after 1-year treatment. CONCLUSIONS: The likelihood of remission and extent of radiographic progression after 1 year was associated with the week 12 DAS28(ESR) response. The DAS28(ESR) response at 12 weeks could be beneficial for identifying patients that are unlikely to respond to prolonged CZP treatment.
27973973 Pentraxin 3 in serum and synovial fluid of patients with rheumatoid arthritis with and wit 2017 Sep OBJECTIVES: Pentraxin 3 (PTX3) is a locally produced multifunctional protein involved in inflammation, matrix deposition, and immunity. As patients with seropositive rheumatoid arthritis (RA) have a more severe disease course and higher risk of joint destruction than seronegative patients, the aim of the present study was to examine differences in PTX3 in synovial fluid (SF) (and serum) in seropositive compared to seronegative RA, and other local markers of inflammation and destruction. METHOD: Ninety-seven RA patients with knee effusion were included. Serum and SF levels of PTX3, as well as serum levels of anti-citrullinated protein antibody and rheumatoid factor of immunoglobulin A and M subclasses, and markers of inflammation and potential destruction in SF: white blood cell counts, tumour necrosis factor, interleukin-6, vascular endothelial growth factor, metalloproteinase 3, and cartilage oligomeric matrix protein, were analysed. In addition, a radiographic knee examination was performed. RESULTS: Seropositive patients had significantly higher PTX3 levels in SF than seronegative patients, whereas there was no difference for serum levels. SF-PTX3 levels correlated with disease activity and with local inflammatory markers, especially polymorphonuclear cells, and with autoantibody levels. There was no correlation between PTX3 levels in serum and SF. CONCLUSION: The correlation of disease activity and autoantibody levels with SF-PTX3 levels in antibody-positive patients suggests a role for PTX3 in the inflammatory process specifically in seropositive RA joints, and supports the hypothesis that seropositive and seronegative RA are different disease entities. Polymorphonuclear granulocytes may be an important source of PTX3 in RA SF.
25916813 Associations with smoking and shared epitope differ between IgA- and IgG-class antibodies 2015 May OBJECTIVE: Smoking and HLA-DRB1/shared epitope (SE) alleles are risk factors for rheumatoid arthritis (RA) characterized by seropositivity for antibodies targeting citrullinated proteins (ACPAs)/cyclic citrullinated peptides (anti-CCP). Previously, mainly IgG-class antibodies have been studied. IgA-class antibodies are to a great extent related to mucosal immunity. The aim of this study was to explore interrelations between cigarette smoking, presence of SE, and seropositivity for circulating IgA and/or IgG anti-CCP antibodies among patients with early RA, to determine whether ACPAs of the IgA subclass are regulated by different mechanisms than those of the IgG subclass. METHODS: Two cohorts of patients with early RA, from the first Epidemiological Investigations of RA trial (n = 1,663) and the second Early Intervention in RA trial (n = 199), were grouped into 4 subsets based on anti-CCP subclass status (IgG-/IgA-, IgG-/IgA+, IgG+/IgA-, and IgG+/IgA+), and each subset was compared with regard to associations with smoking (current and former) and presence of SE. Interaction between smoking and SE was calculated using the attributable proportion (AP) due to interaction (assessing deviation from additivity of effects). RESULTS: Smoking was overrepresented among IgA anti-CCP-positive RA patients, regardless of whether IgG anti-CCP were present, whereas in patients with IgG anti-CCP alone, no association with smoking was found. SE alleles were overrepresented among IgG anti-CCP-positive patients, regardless of IgA anti-CCP status, and was not seen in patients with IgA anti-CCP alone. An interaction between ever smoking and SE was found with regard to the risk of IgG+/IgA+ RA (AP 0.5, 95% confidence interval 0.4, 0.6). No significant interaction was observed with regard to the risk of IgG-/IgA+ RA or IgG+/IgA- RA. CONCLUSION: In patients with RA, a history of ever smoking was associated with seropositivity for IgA anti-CCP antibodies, whereas presence of SE was associated with seropositivity for IgG anti-CCP antibodies. An interaction between ever smoking and the SE was limited to the RA subset characterized by seropositivity for both IgG and IgA anti-CCP. These findings provide novel evidence that anti-CCP-positive RA can be divided into at least 3 serologically distinct subsets associated with different risk factors, indicating different modes of pathogenesis in RA.
27493266 Liposomal Treatment of Experimental Arthritis Can Be Monitored Noninvasively with a Radiol 2017 Jan Rheumatoid arthritis is a chronic autoimmune disorder resulting in synovial inflammation. Fibroblast activation protein (FAP) is overexpressed by fibroblastlike synoviocytes in arthritic joints. Radioimmunoimaging with an anti-FAP antibody might be used to monitor the response to therapy, thus enabling tailored therapy strategies and therapeutic outcomes. The aim of this study was to assess whether a radiolabeled anti-FAP antibody could be used to monitor the efficacy of treatment with long-circulating liposomes (LCL) containing prednisolone phosphate (PLP-LCL) in a mouse model of arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in male DBA/1J mice. Mice were treated with a single injection (10 mg/kg) of PLP-LCL or empty LCL as a control. SPECT and CT images were acquired 24 h after injection of (99m)Tc-labeled succinimidyl-hydrazinonicotinamide ((99m)Tc-S-HYNIC)-conjugated anti-FAP antibody 28H1 at 2, 5, and 9 d after treatment. The uptake of (99m)Tc-S-HYNIC-28H1 in all joints was quantified and correlated with macroscopic arthritis scores. RESULTS: Treatment of CIA with PLP-LCL significantly suppressed joint swelling. At just 1 d after treatment, the macroscopic arthritis scores had decreased by 50%. Scores decreased further, to only 10% of the initial scores, at 5 and 9 d after treatment. In contrast, macroscopic arthritis scores had increased up to 600% in untreated mice at 9 d after the injection of empty LCL. (99m)Tc-S-HYNIC-28H1 uptake ranged from 1.5 percentage injected dose per gram in noninflamed joints to 22.6 percentage injected dose per gram in severely inflamed joints. The uptake of radiolabeled 28H1 in inflamed joints (percentage injected dose) correlated with the arthritis score (Spearman ρ, 0.77; P < 0.0001). Moreover, the uptake of (99m)Tc-S-HYNIC-28H1 was slightly increased at 9 d after therapy but was not seen macroscopically, indicating that SPECT/CT imaging might be more sensitive than the macroscopic arthritis scoring method. CONCLUSION: SPECT/CT imaging with (99m)Tc-S-HYNIC-28H1 specifically monitored the response to therapy, and tracer accumulation correlated with the severity of inflammation. In addition, SPECT/CT imaging was potentially more sensitive than the macroscopic arthritis scoring method. This study showed that SPECT/CT with (99m)Tc-S-HYNIC-28H1 could be used to noninvasively monitor the course of CIA in mice.
27133160 Perioperative Complications in Patients With Inflammatory Arthropathy Undergoing Total Hip 2016 Oct BACKGROUND: Limited information exists comparing the short-term complications of the different inflammatory arthropathies (IAs) after total hip arthroplasty (THA). Our objectives were to (1) compare perioperative complications and (2) determine the most common complications between the different IA subtypes compared with patients with osteoarthritis (OA) undergoing primary THA. METHODS: The Nationwide Inpatient Sample was used to identify 2,102,238 patients undergoing elective, unilateral THA between 2002 and 2011. Of these, 86,671 (4%) had an IA, including rheumatoid arthritis (RA), psoriatic arthritis, juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE). Preoperative diagnosis, comorbidities, and postoperative complications were determined using International Classification of Disease Clinical Modification version 9 codes. The prevalence of in-hospital medical and orthopedic complications was compared between patients with an IA and OA. RESULTS: When compared with patients with OA, patients with RA, JIA, SLE, and AS had significantly more inpatient medical and orthopedic complications immediately after THA (P < .01). Patients with JIA had the highest orthopedic complication rate (2.8%). Specific orthopedic complications by subtype included wound dehiscence for RA and AS periprosthetic fractures for JIA and increased mortality for SLE patients. There were no significant differences in medical or orthopedic complications seen in patients with psoriatic arthritis. CONCLUSION: Differences exist in postoperative inpatient medical and orthopedic complications among patients with different types of IAs after THA. Our results point out the importance of preoperative optimization in patients with IA and monitoring for selective postoperative complications.
25649145 IL-6-driven STAT signalling in circulating CD4+ lymphocytes is a marker for early anticitr 2016 Feb OBJECTIVES: A previously identified signal transduction and activator of transcription-3 (STAT3) target-enriched gene signature in circulating CD4+ T cells of patients with early rheumatoid arthritis (RA) was prominent in autoantibody-negative individuals. Here, interleukin (IL)-6-mediated STAT signalling was investigated in circulating lymphocytes of an independent early arthritis patient cohort, seeking further insight into RA pathogenesis and biomarkers of potential clinical utility. METHODS: Constitutive and IL-6-induced expression of phosphorylated STAT1 (pSTAT1) and pSTAT3 was determined in T and B cells using Phosflow cytometric analysis in patients with RA and controls. Contemporaneous levels of serum cytokines were measured by immunoassay. Induced gene expression was measured in cultured CD4+T cells by quantitative real-time PCR. RESULTS: Among circulating lymphocytes of 187 patients with early arthritis, constitutive pSTAT3 correlated with serum IL-6 levels maximally in CD4+ T cells. Increased constitutive pSTAT3, but not pSTAT1, was observed in circulating CD4+ T cells of patients with early anticitrullinated peptide autoantibody (ACPA)-negative RA compared with disease controls, and these levels decreased alongside markers of disease activity with IL-6R-targeted treatment. Among patients presenting with seronegative undifferentiated arthritis (UA) the ratio of constitutive pSTAT3:pSTAT1 in CD4+ T cells contributed substantially to an algorithm for predicting progression to classifiable RA during a median of 20 months follow-up (area under receiver operator characteristic curve=0.84; p<0.001). CONCLUSIONS: Our findings support a particular role for IL-6-driven CD4+ T cell activation via STAT3 during the induction of RA, particularly as a feature of ACPA-negative disease. CD4+ T cell pSTAT measurements show promise as biomarkers of UA-RA progression and now require independent validation.
27682064 Home Environment as a Source of Life-Threatening Azole-Resistant Aspergillus fumigatus in 2017 Jan 1 A case of fatal aspergillosis due to a TR(46)/Y121F/T289A azole-resistant Aspergillus fumigatus is reported. Environmental investigations at the patient's residence led to the recovery of TR(46)/Y121F/T289A isolates, genotypically indistinguishable from the clinical isolate, supporting for the first time the direct role of household as potential source of azole-resistant invasive aspergillosis.
26140470 Risk factors for treatment failure in osteoporotic patients with rheumatoid arthritis. 2016 OBJECTIVE: No available anti-osteoporotic medication has been shown to completely prevent declines in bone mineral density (BMD) and the resulting increased risk of fracture. The objective of this study was to investigate the risk factors for treatment failure in osteoporotic patients with rheumatoid arthritis (RA). METHODS: A retrospective cohort study of 103 patients with RA and osteoporosis was conducted. Patients were divided into two groups for comparison: those whose osteoporosis treatment was effective and those whose treatment failed. Risk factors for treatment failure were identified by univariate and multivariate logistic regression using variables that differed significantly between the groups. RESULTS: Osteoporosis treatment failed in 66 of 103 patients (64.1%). During 14.01 months of follow-up, non-adherence to bisphosphonate use was the most powerful risk factor for treatment failure. Daily glucocorticoid dosage ≥ 7.5 mg/day before the first BMD measurement, immobilization > 3 months, and Disease Activity Score in 28 joints (DAS28) ≥ 3.2 were also significantly related to treatment failure. CONCLUSION: Our findings indicate that osteoporosis treatment fails frequently in RA patients and adherence to bisphosphonate use, daily glucocorticoid dosage, immobilization, and DAS28 score should be taken into consideration when treating osteoporotic patients with RA.
25648973 Incidence of herpes zoster in Japanese patients with rheumatoid arthritis from 2005 to 201 2015 Jul OBJECTIVE: To clarify the incidence and the risks of herpes zoster infection in Japanese patients with rheumatoid arthritis (RA). METHODS: By using a self-report of occurrence of herpes zoster in patients with RA in a large observational cohort study from 2005 to 2010, the standardized incidence rate was calculated. A Cox model was used to analyze risk factors for occurrence of herpes zoster. RESULTS: A total of 7,986 patients (female 83.1%) accumulated 30,140 patient-years of observation, and 366 events were confirmed. The standardized incidence rate per 1,000 patient-years was 9.1 (95% confidence interval (CI) 6.2-12.9) in total, 7.8 (3.6-14.8) in men, and 10.3 (6.8-15.0) in women. The risk factors for herpes zoster were age [/10 years: Hazard ratio (HR) 1.268, 95% CI 1.153-1.393, p < 0.0001), high disease activity compared with remission (HR 1.642, 95% CI 1.067-2.528, p < 0.05), prednisolone (< 5 mg/day compared with 0 mg/day: HR 1.531, 95% CI 1.211-1.936, p < 0.001; ≥ 5 mg/day compared with 0 mg/day: HR 1.471, 95% CI 1.034-2.093, p < 0.05), and methotrexate (HR 1.382, 95% CI 1.076-1.774, p < 0.05). CONCLUSION: This study quantified the historical incidence and risk for herpes zoster in Japanese RA patients, and is a benchmark for future studies.
27752107 Folylpolyglutamate synthase is a major determinant of intracellular methotrexate polygluta 2016 Oct 18 We investigated major determinants of the intracellular concentrations of methotrexate polyglutamates (MTXPGs) in patients with rheumatoid arthritis (RA). In 271 RA patients on stable oral low dose weekly pulse MTX therapy, the concentrations of MTXPGs in red blood cells (RBCs) were measured by liquid chromatography-electrospray ionization-tandem mass spectrometry. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed to determine the genotypes of solute carrier family 19 member 1 (SLC19A1), folylpolyglutamate synthase (FPGS), and gamma-glutamyl hydrolase (GGH). The mean total MTXPG concentration and the concentrations of individual MTXPGs increased dose-dependently, but reached a plateau at MTX doses >10 mg weekly. The MTXPG3-5/1-2 ratio was lower in patients with adverse events related to MTX than in patients without adverse events. Three polymorphisms of FPGS significantly influenced the MTXPG3-5/1-2 ratio in RBCs, while polymorphisms of SLC19A1 and GGH had no impact. The minor allele frequencies of 2 FPGS genotypes were significantly increased in our patients compared with a Caucasian population. FPGS may have a major role in regulating intracellular polyglutamation of MTX in RA patients receiving low-dose weekly MTX therapy.
27282753 Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identi 2016 Jun 10 Stratifying patients on the basis of molecular signatures could facilitate development of therapeutics that target pathways specific to a particular disease or tissue location. Previous studies suggest that pathogenesis of rheumatoid arthritis (RA) is similar in all affected joints. Here we show that distinct DNA methylation and transcriptome signatures not only discriminate RA fibroblast-like synoviocytes (FLS) from osteoarthritis FLS, but also distinguish RA FLS isolated from knees and hips. Using genome-wide methods, we show differences between RA knee and hip FLS in the methylation of genes encoding biological pathways, such as IL-6 signalling via JAK-STAT pathway. Furthermore, differentially expressed genes are identified between knee and hip FLS using RNA-sequencing. Double-evidenced genes that are both differentially methylated and expressed include multiple HOX genes. Joint-specific DNA signatures suggest that RA disease mechanisms might vary from joint to joint, thus potentially explaining some of the diversity of drug responses in RA patients.
24728331 Predicting the development of clinical arthritis in anti-CCP positive individuals with non 2015 Sep OBJECTIVES: To monitor progression to inflammatory arthritis (IA) in individuals with non-specific musculoskeletal (MSK) symptoms and positive anticyclic citrullinated peptide (anti-CCP) antibodies. To develop a pragmatic model to predict development of IA in this patient group. METHODS: In this prospective observational cohort, patients with new non-specific MSK symptoms and positive anti-CCP were recruited from regional primary care and secondary care referrals. Clinical, imaging and serological parameters were assessed at baseline. Cox regression analysis was performed to identify predictors of progression to IA and develop a risk score to stratify patients at presentation. FINDINGS: 100 consecutive patients (73 women, mean age 51 years) were followed up for median 19.8 months (range 0.1-69.0); 50 developed IA after a median 7.9 months (range 0.1-52.4), 34 within 12 months. The majority (43/50) fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis. A model for progression to IA was devised using four variables: tenderness of hand or foot joints, early morning stiffness ≥30 min, high-positive autoantibodies, and positive ultrasonographic power Doppler signal. None of the five individuals at low risk (score 0) progressed to IA, compared with 31% of 29 at moderate risk (1-2) and 62% of 66 at high risk (≥3). Adding shared epitope increased the number at low risk (score 0-1; 0/11 progressed). CONCLUSIONS: In patients presenting with non-specific MSK symptoms and anti-CCP, the risk of progression to IA could be quantified using data available in clinical practice. The proposed risk score may be used to stratify patients for early therapeutic intervention. TRIAL REGISTRATION NUMBER: NCT02012764 at ClinicalTrials.gov.
25339123 An Internet-based technique for the identification of persons with symptoms of inflammator 2015 Mar Identifying persons with early rheumatoid arthritis (RA) is a major challenge. The role of the Internet in making decisions about seeking care has not been studied. We developed a method for early diagnosis and referral using the Arthritis Foundation's website. A person with less than 3 months of joint pain symptom who has not yet sought medical attention was screened. Prescreened persons are linked to a self-scoring questionnaire and get a "likelihood" of RA statement. If "likely," the person is offered a free evaluation and biomarker testing performed by Quest Diagnostics. The system available only to Massachusetts's residents yielded a small steady flow of screen-positive individuals. Over 21 months, 43,244 persons took the Arthritis Foundation website prescreening questionnaire; 196 were from Massachusetts and 60 took the self-scoring algorithm. Of the 48 who screened positive, 29 set up an appointment for a free evaluation, but six never came in. Twenty-four subjects were evaluated and diagnosed independently by three rheumatologists. One met the 1987 American College of Rheumatology (ACR) criteria for RA and two met the 2010 ACR/EULAR RA criteria. The 24 examined individuals were contacted at a minimum of 1 year and asked to redo the case-finding questionnaire and asked about their health resource utilization during the interval. Seventeen of the 24 subjects responded, and 10 had seen a health professional. Three of the 17 had a diagnosis of RA; all were on at least methotrexate. Internet case finding was useful in identifying new potential RA cases. The system's performance characteristics are theoretically limited only by the number of study sites available. However, the major barrier may be that seeing a health professional is not a priority for many individuals with early symptoms.
27209012 Discordance between patient and physician assessments of global disease activity in rheuma 2016 May 21 BACKGROUND: Discordance between patient and physician ratings of rheumatoid arthritis (RA) severity occurs in clinical practice and correlates with pain scores and measurements of joint disease. However, information is lacking on whether discordance impacts patients' ability to work. We evaluated the discordance between patient and physician ratings of RA disease activity before and after treatment with etanercept and investigated the associations between discordance, clinical outcomes, and work productivity. METHODS: In the PRESERVE clinical trial, patients with moderate RA received open-label etanercept 50 mg once weekly plus methotrexate for 36 weeks. Baseline and week-36 disease characteristics and clinical and work productivity outcomes were categorized according to week-36 concordance category, defined as positive discordance (patient global assessment - physician global assessment ≥2), negative discordance (patient global assessment - physician global assessment ≤ -2), and concordance (absolute difference between the two disease activity assessments = 0 or 1). Correlations between discordance, clinical outcomes, and predictors of discordance were determined. RESULTS: At baseline, 520/762 (68.2 %) patient and physician global assessment scores were concordant, 194 (25.5 %) were positively discordant, and 48 (6.3 %) were negatively discordant. After 36 weeks of therapy, 556/763 (72.9 %) scores were concordant, 189 (24.8 %) were positively discordant, and 18 (2.4 %) were negatively discordant. Patients with week-36 concordance had the best 36-week clinical and patient-reported outcomes, and overall, the greatest improvement between baseline and week 36. Baseline pain, swollen joint count, duration of morning stiffness, fatigue, and patient general health significantly correlated with week-36 discordance, p < 0.0001 to p < 0.05. Additionally, baseline pain, patient general health, and C-reactive protein were predictors of week-36 discordance (odds ratios 1.22, 1.02, and 0.98, respectively). For the employed patients, percent impairment while working and percent overall work impairment were highest (greatest impairment) at baseline and 36 weeks in the group with positive discordance. CONCLUSIONS: The percentage of patients with concordance increased after 36 weeks of treatment with etanercept, with concordant patients demonstrating the greatest improvement in clinical and patient-reported outcomes. Discordance correlated with several measures of disease activity and was associated with decreased work productivity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00565409 . Registered 28/11/2007.
24754275 Association of polymorphisms in SPARC and NLRP2 genes with rheumatoid arthritis in a Chine 2015 Jan OBJECTIVES: To investigate the association of the polymorphisms in SPARC and NLRP2 with rheumatoid arthritis (RA) in a Chinese Han population. METHODS: Four single nucleotide polymorphisms (SNPs) covering SPARC and three SNPs covering NLRP2 were investigated in 624 Chinese Han RA patients and 1920 healthy controls. RESULTS: The A allele at SPARC rs3210714, SPARC rs11950384, NLRP2 rs2217659, and NLRP2 rs703468 were linked to reduced risk of RA (p = 0.0016, p = 0.0051, p < 0.0001, and p = 0.0033, respectively). Under the recessive model, the A/A genotype of rs3210714, rs11950384, rs2217659, and rs703468 were relevant with RA (p = 0.0071, p = 0.017, p < 0.0001 and p = 0.0066, respectively). Haplotype analysis identified the SPARC GGCG haplotype, AAAA haplotype were associated with the risk for RA (p < 0.0001 and p = 0.0015, respectively), while the risk of RA was lower for carriers of the GAAA haplotype (p < 0.0001), AACG haplotype (p < 0.0001), and the AGCG haplotype (p < 0.0001). The NLRP2 GG haplotype was a risk factor (p < 0.0001), while the GA haplotype and the AG haplotype were associated with lower risk of RA (p < 0.0001 and p = 0.0017, respectively). There was no significant difference between the RA patients and the controls in polymorphisms of rs7719521, rs1978707, and rs269913. CONCLUSION: This study indicates that polymorphisms in SPARC and NLRP2 are related to RA susceptibility in a Chinese Han population.