Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
22245951 Progression of cervical instabilities in patients with rheumatoid arthritis 5.7 years afte 2012 Sep We reviewed 101 rheumatoid arthritis (RA) patients who had undergone their first lower limb arthroplasty between 1990 and 2002. None of the patients had received immunosuppressant or biological drugs. Preoperative and follow-up cervical spine radiographs had been performed (more than 2 years after the arthroplasty). Cervical spine instabilities were found in 62 and 82 patients, and a posterior atlantodental interval (PADI) of <14 mm was present in 20 and 22 patients in the respective radiographs. The presence of cervical spine instabilities and PADI <14 mm were correlated with a higher modified Lansbury index (LI) both preoperatively and at final follow-up. Patients with no cervical spine instability throughout the follow-up had a lower average LI. Patients with atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS) had more joint arthroplasties at final follow-up compared with other patients. The percentage of patients with single and multiple cervical instabilities increased at final follow-up. The incidence of cervical spine instabilities in RA patients requiring a lower limb arthroplasty is extremely high, with progression of these instabilities after the procedure. There is a correlation between the severity of RA activity in peripheral joints and the severity of cervical spine instabilities.
21996148 Use of administrative claims data for comparative effectiveness research of rheumatoid art 2011 Observational studies, particularly those using large administrative claims databases, have become increasingly popular sources of comparative effectiveness or comparative safety research. Studies using claims data often face challenges and criticisms due to the lack of certain clinical information, such as lifestyle risk factors, disease severity, and questionable accuracy of disease diagnoses. A novel, claims-based algorithm to evaluate the clinical effectiveness of rheumatoid arthritis medications has been developed and its performance seems promising, although further validation is needed.
22407628 [Usefulness of magnetic resonance imaging in the diagnosis of early rheumatoid arthritis: 2012 Feb BACKGROUND: Diagnosing early rheumatoid arthritis is difficult and radiographic signs are often late. MRI detects erosions at an early stage and visualizes synovitis, bone edema and tenosynovitis. AIM: To assess the value of MRI for diagnosis of early forms of rheumatoid arthritis. METHODS: Prospective study involving 20 patients who had non erosive rheumatoid arthritis lasting for less than 2 years. MRI of the hand was performed by sequences coronal and axial T1-weighted, T2 with saturated fat signal (FatSat) FatSat and T1 with gadolinium injection. RESULTS: The median age of patients was 52 years and sex ratio M/F of 0.05. The median disease duration was 9 months. Ten patients had antibodies Anti-Cyclic citrullinated protein positive. The MRI was abnormal in 75% of patients. This review found 36 erosions which 50% were in carpal bones, 55 joints with synovitis mainly localized midcarpal and metacarpophalangeal. Bone edema was found mainly in carpal bones. Tenosynovitis affected most frequently the flexor tendons. Seventy percent of patients without anti-Cyclic citrullinated protein had a pathological MRI. CONCLUSION: MRI has an important role in detecting infraradiological lesions in early RA. This contributes to early diagnosis and initiation effective treatment.
20961687 The development of fibromyalgia--I: examination of rates and predictors in patients with r 2011 Feb We determined rates and predictors of future development of fibromyalgia in patients with rheumatoid arthritis (RA). After excluding patients with fibromyalgia and those with high levels of fibromyalgia symptoms (fibromyalgianess score>10) at baseline, we studied fibromyalgia development in 9739 RA patients during 42,591 patient-years of follow-up. We defined fibromyalgia using a modification of the ACR 2010 fibromyalgia criteria. We used Cox regression to predict future fibromyalgia, and examined the accuracy of predictions using Harrell's C concordance coefficient. At the last observation, 7.4% of patients satisfied criteria, although 19.8% satisfied criteria at some point during follow-up, an incidence rate of 5.3 (95% CI 5.1, 5.6) per 100 patients years, and at rates that were similar in men (7.0%) and women (8.1%). Among those satisfying criteria, during 11,363 years of follow-up from the time of first fibromyalgia diagnosis, half of follow-up time was fibromyalgia+and was associated with markedly abnormal RA variable and FM variable scores. Demographic factors were weak predictors of fibromyalgia (C=0.604). Demographic plus RA variables (C=0.720) and demographic plus fibromyalgia variables (C=0.765), and all predictors (C=0.782) increased accuracy. Clinically important hazard ratios were noted for cognition, depression, comorbidity, and high levels of RA and FM continuous variables Overall, study results indicate that multiple, inter-correlated factors that include social disadvantage, psychological distress, comorbidity, RA severity, and fibromyalgia variables predict future development of fibromyalgia, but there is little evidence of the effect of underlying causes. After diagnosis, patients move in both directions across the diagnostic criteria cut points.
23345996 Greater prevalence of seropositivity for anti-cyclic citrullinated peptide antibody in una 2013 Jan BACKGROUND/AIMS: This study determined the prevalence and determinants of seropositivity for rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and anti-mutated citrullinated vimentin (anti-MCV) antibody in unaffected first-degree relatives (FDRs) of rheumatoid arthritis (RA) patients. METHODS: A total of 337 subjects (135 with RA and 202 FDRs) were enrolled in this case-control study. Serum RF, anti-CCP antibody, and anti-MCV antibody were assayed. Subjects in multicase families (≥ 2 affected FDRs within the same family) were identified. Multivariate logistic regression analysis was used to identify risk factors associated with RA-related autoantibodies. RESULTS: Seropositivity for RF, anti-CCP antibody, or anti-MCV antibody was detected in 14.4%, 5.0%, or 13.4% of unaffected FDRs, respectively. Anti-CCP antibody seropositivity was more prevalent in FDRs in multicase families (17.8%) than in those not in multicase families (1.3%, p < 0.0001). Significant correlations between RA-associated autoantibodies were detected in the FDR group (between RF and anti-CCP antibody: r = 0.366, p < 0.0001; between RF and anti-MCV antibody: r = 0.343, p < 0.0001; and between anti-CCP antibody and anti-MCV antibody: r = 0.849, p < 0.0001). After adjustment for age and sex, anti-CCP antibody seropositivity in FDRs was significantly associated with being in a multicase family (odds ratio, 49.8; 95% confidence interval, 5.6 to 441.6). CONCLUSIONS: The association between anti-CCP antibody seropositivity in unaffected FDRs and being in a multicase family suggests that genetic and/or environmental factors may increase the risk for RA development in unaffected FDRs.
21994234 Remission and radiographic outcome in rheumatoid arthritis: application of the 2011 ACR/EU 2012 May OBJECTIVES: One goal of remission in rheumatoid arthritis (RA) is to halt joint damage. The authors assessed the progression of radiographic joint damage among RA patients in remission by the new ACR/EULAR criteria (Boolean approach) compared with remission thresholds for the simplified disease activity index (SDAI), clinical disease activity index (CDAI) and disease activity score based on 28 joints and C-reactive protein (DAS28-CRP) in an observational cohort, and evaluated the relationship between time in remission and radiographic joint damage. METHODS: 535 RA patients underwent physical examination and laboratory assessment at baseline, 1 and 2 years. Radiographs at baseline and 2 years were scored by the van der Heijde modified Sharp score (TSS). Positive likelihood ratios for a good radiographic outcome (change in TSS <1 unit/year) were calculated for each of the remission criteria. Radiographic progression was compared between patients in remission at none, one, two and three visits by χ(2) goodness of fit statistics. RESULTS: 20% of patients in ACR/EULAR remission at baseline had radiographic progression, 24% in SDAI remission, 19% in CDAI remission and 30% of patients in DAS28-CRP remission. The positive likelihood ratio for good radiographic outcome was 2.6 for ACR/EULAR criteria, 2.1 for SDAI, 2.8 for CDAI and.1.5 for DAS28-CRP. Reduced radiographic progression was observed for patients with an increasing number of visits in remission (p<0.003 for all criteria, χ(2) goodness of fit statistics). CONCLUSIONS: Patients with RA in remission by any established criteria can experience radiographic progression. An increased number of visits in remission was associated with reduced radiographic damage.
21813548 Association with joint damage and physical functioning of nine composite indices and the 2 2011 Oct OBJECTIVE: To compare nine disease activity indices and the new American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) remission criteria in rheumatoid arthritis (RA) and to relate these to physical function and joint damage progression. METHODS: Five-year data from the BeSt study were used, a randomised clinical trial comparing four treatment strategies in 508 patients with recent-onset RA. Every three months disease activity was assessed with nine indices (Disease Activity Score (DAS), DAS-C reactive proteine (DAS-CRP), Disease Activity Score in 28 joints (DAS-28), DAS28-CRP, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and three DAS versions with adjusted tender joint scores) and categorized into remission, low, moderate and high disease activity (LDA, MDA, HDA). In addition, the recent ACR/EULAR clinical trial and practice remission was assessed 3-monthly with 28 and 68/66 joint counts. For each index, Generalized Estimating Equations analyses were performed to relate disease activity levels and the absence/presence of remission to 3-monthly assessments of physical functioning and annual radiological progression. RESULTS: From the composite indices, CDAI and SDAI were the most stringent definitions of remission and classified more patients as LDA. DAS28 and DAS28-CRP had the highest proportions of remission and MDA and a smaller proportion of LDA. ACR/EULAR remission percentages were comparable to CDAI/SDAI: remission percentages. The variant including CRP and 68/66 joint counts was the most stringent. For all indices, higher levels of disease activity were associated with decreased physical functioning and more radiological damage progression. Despite differences in classification between the indices, no major differences in relation to the two outcomes were observed. CONCLUSION: The associations of nine composite indices and ACR/EULAR remission criteria with functional status and joint damage progression showed high accordance, whereas the proportions of patients classified in the disease activity levels differed.
23085092 A population-based case-control study on the association between rheumatoid arthritis and 2012 Dec OBJECTIVE: Chronic inflammation has been associated with endothelial dysfunction and altered coagulation status. However, at the present time, the data regarding the risk for developing deep vein thrombosis (DVT) in patients with rheumatoid arthritis (RA) is still scanty and conflicted. This study aimed to explore the frequency and association of DVT with RA using a population-based dataset. METHODS: This was a case-control study conducted in Taiwan. A total of 5193 patients with DVT were identified from the Longitudinal Health Insurance Database 2000 (LHID2000) database. In total, 20,772 controls matched with cases in terms of gender, age, and year of index date were randomly selected. We used conditional logistic regression to calculate the odds ratio (OR) for having been previously diagnosed with RA between cases and controls. RESULTS: Of the total 25,965 sampled subjects, 235 (0.9%) had been previously diagnosed with RA. Seventy-seven of these previous diagnoses were found among cases (1.5%) and 158 among controls (0.8%). Conditional logistic regression analysis revealed that cases were more likely to have had prior RA than controls (OR, 1.92; 95% confidence interval [CI], 1.46-2.53; P<.001). After adjusting for hospitalization history, pregnancy, fracture, surgery, cancer, inflammatory bowel disease, heart failure, hypertension, diabetes, coronary heart disease, hyperlipidemia, and renal disease, there was still a significant association between DVT and prior RA (OR, 1.88; 95% CI, 1.42-2.58; P<.001). CONCLUSIONS: We found RA to be significantly associated with DVT. Appropriate management should be taken to minimize the risk of DVT in patients with RA. Further study is needed to confirm our findings.
21816020 The frequency of metabolic syndrome in women with rheumatoid arthritis and in controls. 2011 Aug AIM: To compare the frequency of the metabolic syndrome and its components in a sample of patients with rheumatoid arthritis (RA) and controls. METHODS: This case control study was performed on 188 women over 18 years old: 92 RA patients and 96 healthy controls, from 2006 to 2008. Blood pressure, height, weight and waist circumference were measured. Blood was collected for the measurement of fasting glucose, lipid profile and insulin. The frequency of the metabolic syndrome was determined in case and control groups, using both WHO and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. RESULTS: According to the NCEP criteria, the frequency of metabolic syndrome in RA patients and controls were 27.2% and 35.4%, respectively (P = 0.22). Based on WHO criteria, 19.6% of RA patients and 21.9% of the control group were subject to metabolic syndrome (P = 0.70). The proportion with hypertension was greater in RA patients than the control group. The duration of RA was significantly higher in patients with metabolic syndrome compared to those without metabolic syndrome using both the WHO and NCEP criteria. CONCLUSIONS: There was no evidence of a greater prevalence of metabolic syndrome in RA patients compared with controls in this study. The duration of RA was associated with metabolic syndrome, implicating the role of inflammation in metabolic syndrome development.
22942403 Large-joint damage in patients with early rheumatoid arthritis and its association with tr 2012 Dec OBJECTIVE: To determine the prevalence of large-joint damage and the association with small-joint damage in patients with RA after 8 years of low DAS (≤2.4)-targeted treatment with different treatment strategies. METHODS: Radiological data of 290 patients participating in the BeSt study, a randomized trial comparing initial monotherapy and initial combination therapy strategies, were used. Radiographs of large joints were scored using the Larsen score and of the small joints using the Sharp-van der Heijde score. With multivariate logistic regression analysis, an association between total damage of the small joints and of the large joints was investigated. RESULTS: After 8 years of treatment, damage was observed in 12% of shoulders, 10% of elbows, 26% of wrists, 13% of hips, 18% of knees and 7% of the ankles. Damage in one or more large joints was found in 64% of patients, with a median score of 1. No difference was found between initial monotherapy or combination therapy strategies. There was a significant association between damage progression in small joints and damage to one or more large joints (OR 1.02; 95% CI 1.00-1.04). CONCLUSION: After 8 years of DAS-targeted treatment in early RA patients, large-joint damage was found in 64% of patients and was associated with small-joint damage. Continued DAS-targeted treatment is probably more important in damage suppression than initial treatment strategy. Patients with more damage to hands and feet also have more damage to the large joints.
22730931 The reporting quality of studies investigating the diagnostic accuracy of anti-CCP antibod 2012 Jun 25 BACKGROUND: Recently anti-CCP testing has become popular in the diagnosis of rheumatoid arthritis (RA). However, the inadequate reporting of the relevant diagnostic studies may overestimate and bias the results, directing scientists into making false decisions. The aim of the present study was to evaluate the reporting quality of studies used anti-CCP2 for the diagnosis of RA and to explore the impact of reporting quality on pooled estimates of diagnostic measures. METHODS: PubMed was searched for clinical studies investigated the diagnostic accuracy of anti-CCP. The studies were evaluated for their reporting quality according to STARD statement. The overall reporting quality and the differences between high and low quality studies were explored. The effect of reporting quality on pooled estimates of diagnostic accuracy was also examined. RESULTS: The overall reporting quality was relatively good but there are some essential methodological aspects of the studies that are seldom reported making the assessment of study validity difficult. Comparing the quality of reporting in high versus low quality articles, significant differences were seen in a relatively large number of methodological items. Overall, the STARD score (high/low) has no effect on the pooled sensitivities and specificities. However, the reporting of specific STARD items (e.g. reporting sufficiently the methods used in calculating the measures of diagnostic accuracy and reporting of demographic and clinical characteristics/features of the study population) has an effect on sensitivity and specificity. CONCLUSIONS: The reporting quality of the diagnostic studies needs further improvement since the study quality may bias the estimates of diagnostic accuracy.
22004228 Oxidative stress in systemic lupus erythematosus and rheumatoid arthritis patients: relati 2011 Oct AIM: The present work was undertaken to study the status and contribution of oxidative stress in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. Relationship of the markers of oxidative stress to clinical manifestations, disease activity, damage and medications used were well considered. METHODS: Thirty SLE and 30 RA female patients were included in the study and clinical examination and investigations were performed and disease activity was assessed. Markers of oxidative stress, including malondialdehyde (MDA) and antioxidant scavengers with glutathione (GSH) and glutathione peroxidase (GSH Px) were assessed. RESULTS: Level of MDA, GSH and GSH Px were remarkably altered in RA and SLE patients compared to controls. Markers of increased oxidative stress and impaired antioxidant capacity were profound in RA and significantly reflected disease activity in RA and SLE, with special attention to alopecia and lupus nephritis. RA patients receiving methotrexate had significantly altered parameters and the steroid dose in SLE patients correlated with these markers. CONCLUSION: Oxidative stress was increased and more profound in RA than SLE and could well reflect disease activity, with special attention to SLE patients with alopecia and nephritis. Medications used are closely related to the oxidant/antioxidant imbalance. Considering antioxidants in novel therapeutic strategies is important in SLE and RA patients.
21885509 Patterns of magnetic resonance imaging bone erosion in rheumatoid arthritis--which bones a 2011 Sep OBJECTIVE: To investigate by magnetic resonance imaging (MRI) which bones in wrists and metacarpophalangeal (MCP) joints most frequently show bone erosions, and which most frequently demonstrate erosive progression, in early and established rheumatoid arthritis (RA). METHODS: MRI datasets from 258 RA patients [126 with early RA (disease duration < 6 months)] were analyzed, of whom 223, including 126 with early RA, had 1-year followup MRI. All patients had MRI of one wrist, whereas 86 patients had additional images of 2nd-5th MCP joints, and 46 patients additional images of the contralateral wrist. MRI were evaluated blinded by one reader, according to the OMERACT RA MRI scoring system (RAMRIS) for erosions, and presence/absence of erosions was noted in each bone, as was presence/absence of erosive progression. RESULTS: The capitate, ulna, lunate, triquetrum, and scaphoid were the 5 bones with both most frequent baseline erosions and most frequently demonstrated erosive progression. No bones were without erosions. Patterns of erosions and progression were similar in early and established RA. No major difference between dominant and nondominant wrists was detected. In the fingers, the 2nd-3rd MCP joint most frequently displayed erosions and erosive progression. CONCLUSION: The distribution and frequency of bone erosion and erosive progression as detected by MRI in RA wrists and MCP joints were identified. No pattern differences between early versus established disease and dominant versus nondominant sides were detected. No bones showed erosive progression. Thus, no self-evident simplification of the RAMRIS erosion score was identified. Bone involvement patterns may be considered, when joints are selected for MRI protocols for clinical trials and practice.
21904814 Efficacy of leflunomide addition in relation to prognostic factors for patients with activ 2012 Jan The recommendations of the European League Against Rheumatism (EULAR) for the management of rheumatoid arthritis (RA) suggest a different therapeutic approach to methotrexate (MTX) resistance according to the presence or absence of poor prognostic factors. Retrospectively, in our patients with active early RA (disease activity score in 28 joints (DAS28) > 3.2) that failed to respond to initial MTX monotherapy, we investigated whether leflunomide (LEF) addition had a different efficacy when associated with the presence or absence of poor prognostic factors. Of the 20 patients who received LEF, 15 (2 males and 13 females) tolerated the combination. Five patients had no poor prognostic factors, and 4 (80%) of those patients achieved remission or low disease activity (LDA) according to DAS28 and also a good response with the EULAR criteria. Of the 10 patients with at least one poor prognostic factor, remission or LDA occurred in 4 (40%) of the patients, and a good EULAR response was obtained in 3 (30%) of the patients. By Fisher's exact test, no significant difference was found between the two groups of patients in remission or LDA (p = 0.28) according to DAS28 and a good response (p = 0.12) with the EULAR criteria. In all patients with an inadequate response to the LEF+MTX combination, the substitution of a TNF inhibitor for LEF or the addition of a TNF inhibitor to the combination led to remission or LDA. Large studies are required to investigate the efficacy of LEF addition in relation to prognostic factors in patients with active early RA that did not respond to the initial therapy with MTX alone.
21975789 Pain management for rheumatoid arthritis and cardiovascular or renal comorbidity. 2011 Oct 5 BACKGROUND: Pain in rheumatoid arthritis is common, is often multi-factorial and many different pharmacotherapeutic agents are routinely used for pain management. There are concerns that some of the pain pharmacotherapies currently used may increase the risk of adverse events in people with rheumatoid arthritis and concurrent cardiovascular or renal disease. OBJECTIVES: To systematically assess and collate the scientific evidence on the efficacy and safety of using pain pharmacotherapy in people with rheumatoid arthritis and cardiovascular or renal comorbidities. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 4); MEDLINE, from 1950; EMBASE, from 1980; the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE). We also handsearched the conference proceedings for American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) for 2008-09, and checked the websites of regulatory agencies for reported adverse events, labels and warnings. SELECTION CRITERIA: We considered randomised controlled trials and non-randomised studies comparing the efficacy and safety of pain pharmacotherapies in patients with rheumatoid arthritis, with and without comorbid cardiovascular or renal conditions.In addition, we also considered controlled before-after studies, interrupted time series, cohort and case control studies and case series (N ≥ 20) to assess safety.For the purpose of our review, pain pharmacotherapy was defined as including simple analgesics (such as paracetamol), non-steroidal anti-inflammatory drugs (NSAIDs), opioids or opioid-like drugs (such as tramadol), and neuromodulators (including anti-depressants, anti-convulsants, and muscle relaxants). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results and planned to extract data and appraise the risk of bias of included studies. MAIN RESULTS: We did not identify any studies meeting our inclusion criteria. Many of the trials of NSAIDs explicitly excluded patients with cardiovascular or renal comorbidities.We did identify one trial that reported evidence in mixed populations (including both rheumatoid arthritis and osteoarthritis) taking either diclofenac or etoricoxib. In this study, the presence of cardiovascular disease increased the likelihood of a further cardiovascular event three-fold. Patients with two or more cardiovascular comorbidities showed a two-fold increased likelihood of adverse cardiovascular events. AUTHORS' CONCLUSIONS: There were no trials that specifically compared the efficacy and safety of pain pharmacotherapies for patients with rheumatoid arthritis, with and without comorbid cardiovascular or renal conditions.In the absence of specific evidence in rheumatoid arthritis, current guidelines recommend that NSAIDs be used with caution in the general rheumatoid arthritis population while highlighting the added need for extra vigilance in patients with established cardiovascular disease or risk factors for its development. Current guidelines regarding the use of NSAIDs and opioids in moderate to severe renal impairment should also be applied to the rheumatoid arthritis population.Further research is required to guide clinicians when treating pain in rheumatoid arthritis.
23221583 Rheumatoid arthritis disease measurement: a new old idea. 2012 Dec In many medical treatment areas, the use of treatment targets has led to improved outcomes, including a reduction in end-organ damage. In rheumatology, appropriate targets appear elusive, although preventing joint damage, minimizing disability and improving mortality are end results on which most clinicians would agree. Sophisticated measures of disease activity, particularly in early disease, have only recently been objectively evaluated. Swollen joint count, tender joint count, acute-phase reactants, citrullinated antibody titres (ACPAs), patient and physician assessment of disease activity, radiographs and other imaging modalities such as US and MRI may all be appropriate to measure. A number of composite measures have been proposed as possible or practical methods for defining RA disease activity. Some require testing of acute-phase reactants, but several do not. ACR20/50/70 scores are useful for measuring change from visit to visit, while others (DAS28, HAQ, Simplified Disease Activity Index, Clinical Disease Activity Index and Routine Assessment of Patient Index Data) assess disease activity at a single point. Disease measures have now been used in myriad clinical trials and studies. The FIN-RACo, TICORA, CAMERA and BeSt trials employed measures of disease activity at predetermined points to guide treatment decisions. These trials supported the consistent use of objective measures to derive significant benefits from treat-to-target strategies. The concept that objective measures can guide aggressive treatment to reach a defined optimal end point or target is a strategy that rheumatologists hopefully might now agree is critically important.
22935335 The comparative responsiveness of the patient self-report questionnaires and composite dis 2012 Nov OBJECTIVES: This paper aims to evaluate the internal and external responsiveness of the patient self-report questionnaires, comparatively to the traditional composite indices to assess the activity of rheumatoid arthritis (RA) in everyday practice. METHODS: One hundred and ninety-one RA out-patients completed the clinical arthritis activity (PRO-CLARA) index, the rheumatoid arthritis disease activity index (RADAI), the routine assessment of patient index data (RAPID3), and the patient activity score (PAS). Simultaneously, the disease activity score-28 joints based on CRP (DAS28-CRP) and ESR (DAS28-ESR), the simplified disease activity index (SDAI), the clinical disease activity index (CDAI), and the mean overall index for RA (MOI-RA) were computed for each patient. Sensitivity to change was assessed after 6 months of treatment with disease-modifying anti-rheumatic drugs or biologics. Internal responsiveness was evaluated with the effect size (ES) and standardised response mean (SRM). External responsiveness was investigated by receiver operating characteristic (ROC), in categories of respondents, stratified according to the response on an item on change in overall health. In addition, change scores were compared by calculating correlation coefficients. RESULTS: No significant differences in internal and external responsiveness were found between self-report questionnaires and composite indices. The internal responsiveness of the self-report questionnaires and composite measures was wide, with SRM and ES ranging from 1.03 (RADAI) to 1.80 (DAS28-ESR) and higher than that of the each individual measures. The responsiveness of the PRO-CLARA was equal to the DAS28-ESR, DAS28-CRP, SDAI or MOI-RA, but better than the CDAI. The RADAI and PAS were less responsive than the PRO-CLARA and RAPID3. The area under ROC curve of the PRO-CLARA gives identical results to those provided by other comparator composite indices. The score changes of all combinations were highly correlated (p<0.0001). CONCLUSIONS: The self-report questionnaires showed comparable internal and external responsiveness to the composite activity scores and allow for the detection of rheumatoid disease activity. They appear suitable for clinical decision making, epidemiologic research and clinical trials. Further longitudinal studies are needed to validate these encouraging results.
21343168 Autopathogenic correlation of periodontitis and rheumatoid arthritis. 2011 Jul Recently, a number of studies have pointed to a potential relationship between periodontitis (PO) and RA and vice versa. Both diseases are characterized by chronic inflammation, osseous destruction, damage of the supporting soft tissues, similar cellular immune responses and common immunogenetic findings. Although a definite, methodological report associating these diseases is missing from the literature, it is possible that both diseases share a common aetiopathogenic background. This background includes the post-translation modification citrullination, which guides the conversion of the amino acid arginine to citrulline in certain self-proteins, generating neo-epitope structures. This results in reduced self-tolerance, development of autoimmunity and the production of ACPAs. The current hypothesis suggests that certain oral bacteria induce the citrullination of proteins under the action of the enzyme peptidyl arginine deiminase (PAD), which exists in both Porphyromonas gingivalis and inflammatory cells. Antibodies against citrullinated proteins and peptides constitute a common serological finding in both RA and PO. The aim of this review is to map the immunological and serological profiles of PO, and to unveil the parameters that connect PO with the appearance of RA at clinical, prognostic and pathogenetic levels. Until now, there have been no reports sufficiently mapping the immunological profile of PO and defining its aetiopathogenic connection with RA, although a similarity between the immunological profile of PO and RA is highly expected.
23024017 Osteoclast migration, differentiation and function: novel therapeutic targets for rheumati 2013 Feb RA is a chronic autoimmune disease characterized by joint synovial inflammation and progressive cartilage/bone destruction. Although various kinds of RA drug have been developed worldwide, there are currently no established methods for preventing RA-associated bone destruction, the most severe outcome of this disease. One of the major pathogenic factors in arthritic bone destruction is the enhanced activity of osteoclasts at inflammatory sites. Osteoclasts are bone-resorbing giant polykaryons that differentiate from mononuclear macrophage/monocyte-lineage haematopoietic precursors. Upon stimulation by cytokines, such as M-CSF and RANK ligand, osteoclast precursor monocytes migrate and attach onto the bone surface (migration). They then fuse with each other to form giant cells (differentiation) and mediate bone resorption (function). In this review, we summarize the current understanding regarding the mechanisms underlying these three dynamic steps of osteoclastic activity and discuss novel lines of osteoclast-targeted therapies that will impact future treatment of RA.
23294992 The role of the FcGRIIIa polymorphism in modifying the association between treatment and o 2013 Mar OBJECTIVES: There is an association between the FcGRIIIa polymorphism and the development of rheumatoid arthritis (RA). Studies in non-Hodgkin lymphoma demonstrated a relationship between the FcGRIIIa polymorphism and response to anti-CD20 therapies. However, there are currently no published studies evaluating the relationship between this polymorphism and therapeutic response to treatment with anti-CD20 agents such as rituximab in RA. We conducted a study to identify if the FcGRIIIa polymorphism is associated with rituximab efficacy in patients with RA. METHODS: Subjects with RA treated with rituximab (cases, n=158) or TNF-α antagonist (controls, n=390) were recruited from the Consortium of Rheumatology Researchers of North America. The FcGRIIIa variant was genotyped for all subjects and longitudinal patient outcomes were assessed using the clinical disease activity index (CDAI). We used a linear regression random effects model to estimate CDAI scores over time with multiple time points nested within patient. RESULTS: Similar changes in CDAI were observed across the three FcGRIIIa genotypes for the rituximab treated group (VV [4.56, SD 14.5]), VF (7.44, SD 14.9) and FF (4.75, SD 10.8) (p >0.05)] and the TNF-α antagonist therapy treated group [VV (5.12, SD 14.6), VF (6.77, SD 15.9), and FF (4.36, SD 18.2) (p >0.05). Overall, there were similar changes in CDAI at 6 months for rituximab (-5.91, SD 14.1) and anti-TNFs (-5.77, SD 15.5) (p >0.05). The FcGRIIIa genotype was not significantly associated (p=0.86) with treatment response in rituximab treated RA patients compared with TNF-α antagonist therapy treated patients. Baseline CDAI and number of prior biologics were significant predictors of clinical response over time. CONCLUSIONS: Our finding emphasises the idea that determinants of response to treatment are complex and may be dependent upon genetic and phenotypic interactions. Future studies should analyse the interaction between the FcGRIIIa gene, other neighbouring polymorphisms and other phenotypic and environmental factors.