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ID PMID Title PublicationDate abstract
24782594 Autoantibodies to posttranslational modifications in rheumatoid arthritis. 2014 Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell development in vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential.
22101553 Anti-microtubule organizing center with microtubule by autoimmune target test is also usef 2013 Mar Seropositivity of rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibody (anti-CCP) is one domain of scoring system in new American College of Rheumatology/European League against Rheumatism classification criteria for rheumatoid arthritis (RA). We investigated usefulness of antiperinuclear factor (APF) and autoantibody to microtubule organizing center with microtubule (anti-MTOC-MT), which was detected by autoimmune target (AIT) test, as serological markers for the diagnosis of early RA. The test results of 3,503 patients from the outpatient clinic of The Hospital for Rheumatic Diseases who underwent test for RF, APF, anti-CCP and anti-MTOC-MT simultaneously for the work-up of RA were analyzed. Four kinds of tests showed same results only in 53.1% (1,861/3,503) of all subjects. The kappa coefficient between each test was distributed from -0.011 to 0.622. The agreement was best between RF and anti-CCP (kappa coefficient: 0.622), but the agreement was poor between anti-MTOC-MT and other 3 tests (kappa coefficient: 0.007 to -0.025). In both of RF- and anti-CCP-negative patients, the patients who showed positive result for APF were 4.6% (160/3,503) and for anti-MTOC-MT were 13.2% (464/3,503). RF and anti-CCP positivity could not include all of APF and anti-MTOC-MT positivity. Anti-MTOC-MT detected by AIT test was independent serological marker, and it might be also helpful for the diagnosis of early RA. Therefore, the combined detection of all four serologic markers can be useful for the evaluation of suspected RA patients.
23547216 Longterm effects of rituximab on B cell counts and autoantibody production in rheumatoid a 2013 May OBJECTIVE: To assess the efficacy and safety of longterm rituximab (RTX) therapy for rheumatoid arthritis (RA) and study correlations among B cell depletion, clinical response, and autoantibody production. METHODS: Seventy-seven patients with moderate or high RA activity received RTX and were re-treated every 6 months regardless of clinical response. All patients received at least 5 cycles. We assessed 28-joint Disease Activity Score (DAS28), IgM rheumatoid factor (RF), and anticitrullinated protein antibody (ACPA) levels at baseline, after 15 days, and then every 6 months for 24 months. Absolute CD19+ B lymphocyte counts were determined in 50 patients using high-sensitivity flow cytometry (hsFACS) by reading 100,000 events. RESULTS: After 6, 12, 18, and 24 months, 51.6%, 51.9%, 73.3%, and 83.8% of patients, respectively, showed good European League Against Rheumatism responses. Significant and sustained decreases in IgM RF and ACPA levels were observed as early as 6 months and 12 months, respectively. The baseline mean absolute B cell number was 0.234 g/l. B cell numbers diminished significantly after the very first infusion by Day 15 (0.104 g/l; p = 0.007); they further decreased until 24 months (0.0013 g/l; p < 0.001). One RTX infusion resulted in incomplete depletion in 76.7% of patients. Upon RTX treatment, changes in CD19+ B cell numbers positively correlated with changes in DAS28 (r = 0.963, p = 0.008) and IgM RF (r = 0.859, p = 0.028), but not with changes in ACPA production (r = 0.726, p = 0.102). The correlations between B cell numbers and DAS28 were observed in both ACPA-seropositive (r = 0.999, p < 0.0001) and ACPA-negative patient subpopulations (r = 0.962, p = 0.009). The correlation between CD19+ cell numbers and IgM RF was observed only in the ACPA-positive population (r = 0.944, p = 0.005) but not in seronegative patients (r = 0.398, p = 0.435). No safety issues arose. CONCLUSION: In RA, clinical response to RTX is associated with the extent of B cell depletion and with autoantibody production. Changes in CD19+ B cell numbers correlate with those in disease activity and, in seropositive patients, also with IgM RF, but not with ACPA production. We found that hsFACS may be a useful method to more accurately assess incomplete B cell depletion.
25028382 Are rheumatoid arthritis patients discernible from other early arthritis patients using 1. 2014 Aug OBJECTIVE: Magnetic resonance imaging (MRI) is increasingly used in rheumatoid arthritis (RA) research. A European League Against Rheumatism (EULAR) task force recently suggested that MRI can improve the certainty of RA diagnosis. Because this recommendation may reflect a tendency to use MRI in daily practice, thorough studies on the value of MRI are required. Thus far no large studies have evaluated the accuracy of MRI to differentiate early RA from other patients with early arthritis. We performed a large cross-sectional study to determine whether patients who are clinically classified with RA differ in MRI features compared to patients with other diagnoses. METHODS: In our study, 179 patients presenting with early arthritis (median symptom duration 15.4 weeks) underwent 1.5T extremity MRI of unilateral wrist, metacarpophalangeal, and metatarsophalangeal joints according to our arthritis protocol, the foot without contrast. Images were scored according to OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) by 2 independent readers. Tenosynovitis was also assessed. The main outcome was fulfilling the 1987 American College of Rheumatology (ACR) criteria for RA. Test characteristics and areas under the receiver-operator-characteristic curves (AUC) were evaluated. In subanalyses, the 2010 ACR/EULAR criteria were used as outcome, and analyses were stratified for anticitrullinated protein antibodies (ACPA). RESULTS: The ACR 1987 criteria were fulfilled in 43 patients (24.0%). Patients with RA had higher scores for synovitis, tenosynovitis, and bone marrow edema (BME) than patients without RA (p < 0.05). ACPA-positive patients had more BME (median scores 6.5 vs. 4.25, p = 0.016) than ACPA-negative patients. For all MRI features, the predictive value for the presence of RA was low (< 50%). For all MRI features the AUC were < 0.70. Patients who fulfilled ACR/EULAR 2010 criteria but not ACR87 criteria for RA had less synovitis than patients who were positive for RA according to both sets of criteria (p = 0.029). CONCLUSION: Although patients with RA had higher scores of MRI inflammation and ACPA-positive patients had more BME, the severity of MRI inflammation assessed according to RAMRIS does not accurately differentiate patients with RA from other early arthritis patients.
24729397 Symptom complexes in patients with seropositive arthralgia and in patients newly diagnosed 2014 Sep OBJECTIVE: The aim of this study was to explore symptoms and symptom development during the earliest phases of RA in patients with seropositive arthralgia and patients newly diagnosed with RA. METHODS: Interviews were conducted with 15 seropositive patients (anti-CCP positive, and often with arthralgia) and 11 newly presenting RA patients [classified according to the 2010 ACR/European League Against Rheumatism (EULAR) criteria]. Feedback procedures shared the experiences of seropositive arthralgia patients with early RA patients and vice versa. Data were analysed using thematic analysis. RESULTS: Symptoms common to both groups included joint pain, psychological distress, muscle cramps, abnormal skin sensations, stiffness, loss of motor control, weakness, fatigue and sleeping difficulties. Also, patterns of symptom evolution and the order of symptom development were described. Seropositive arthralgia patients described pain as annoying, while RA patients described how the severity of pain intensified before diagnosis, to the point where symptoms were psychologically distressing. Patients with seropositive arthralgia described reddening of the skin and burning sensations that they felt were indicative of the onset of swelling. Intense pain appeared to precede the onset of swelling for those with RA, which was often palindromic and travelled between joints until it later became persistent. CONCLUSION: This study highlights the breadth of symptoms that constitute the earliest phases of RA. Further research is needed to develop measures of symptom patterns and clusters to allow the predictive utility of symptoms to be assessed and to allow the integration of aspects of the patient's history into evidence-based investigative and management algorithms for use in primary and secondary care.
25451821 [Monitoring the functional capacity of patients with rheumatoid arthritis for three years] 2015 Jan OBJECTIVE: To quantify modification of functional capacity in a three year period in a group of patients with rheumatoid arthritis (RA) using HAQ and EPM-ROM inventories. METHODS: Forty patients with RA on methotrexate (MTX) as disease-modifying anti rheumatic drug (DMARD) were followed for up to three years. The functional status was assessed at the beginning and end of the period by HAQ and EPM-ROM. RESULTS: Thirty two patients were retrieved, with initial HAQ score of 1.14±0.49 (mean±SD) and EPM-ROM score of 5.8±2.75. After an average period of three years, the HAQ score was 1.13±0.49 and EPM-ROM score, 6.81±3.66. In the subgroup of seven patients submitted to orthopedic surgery, HAQ score decreased from 0.84±0.72 to 1.64±0.56 and the EPM-ROM score, from 5.8±1.80 to 8.3±0.74. In the subgroup of non-operated patients, HAQ score varied from of 1.2±0.45 to 1.07±0.70 and EPM-ROM score, from 5.7±3.06 to 6.4±3.90. CONCLUSION: In a group of RA patients in use of only MTX as DMARD, there was little change on HAQ score and EPM-ROM scores over the average period of three years. Worsening functional capacity was observed in the group of operated patients in comparison to the not operated ones. This fact alerts us to the need for use of broader therapeutic regimens availability of musculoskeletal surgeries in a timely manner in patients with RA.
25086079 Tumor necrosis factor-α inhibitor treatment and the risk of incident cardiovascular event 2014 Nov OBJECTIVE: To compare the risk of cardiovascular (CV) events between use of tumor necrosis factor-α inhibitors (TNFi) and nonbiologic disease-modifying antirheumatic drugs (DMARD) in patients with early rheumatoid arthritis (RA). METHODS: A nested case-control study was conducted using data from Truven's MarketScan commercial and Medicare claims database for patients with early RA who started treatment with either a TNFi or a nonbiologic DMARD between January 1, 2008, and December 31, 2010. Date of CV event diagnosis for cases was defined as the event date, and 12 age-matched and sex-matched controls were sampled using incidence density sampling. Drug exposure was defined into the following mutually exclusive categories hierarchically: (1) current use of TNFi (with or without nonbiologics), (2) past use of TNFi (with or without nonbiologics), (3) current use of nonbiologics only, and (4) past use of nonbiologics only. Current use was defined as any use in the period 90 days prior to the event date. Conditional logistic regression models were used to derive incidence rate ratios (IRR). RESULTS: From the cohort of patients with early RA, 279 cases of incident CV events and 3348 matched controls were identified. The adjusted risk of CV events was not significantly different between current TNFi users and current nonbiologic users (IRR 0.92, 95% CI 0.59-1.44). However, past users of nonbiologics showed significantly higher risk compared to current nonbiologic users (IRR 1.47, 95% CI 1.04-2.08). CONCLUSION: No differences in the CV risk were found between current TNFi and current nonbiologic DMARD treatment in patients with early RA.
25608624 The supplementary therapeutic DMARD role of low-dose glucocorticoids in rheumatoid arthrit 2014 Nov 13 The management of rheumatoid arthritis (RA) is primarily based on the use of disease-modifying antirheumatic drugs (DMARDs), mainly comprising synthetic chemical compounds (that is, methotrexate or leflunomide) and biological agents (tumor necrosis factor inhibitors or abatacept). On the other hand, glucocorticoids (GCs), used for decades in the treatment of RA, are effective in relieving signs and symptoms of the disease, but also interfere with radiographic progression, either as monotherapy or in combination with conventional synthetic DMARDs. GCs exert most of their biological effects through a genomic action, using the cytosolic GC receptor and then interacting with the target genes within target cells that can result in increased expression of regulatory--including anti-inflammatory--proteins (transactivation) or decreased production of proinflammatory proteins (transrepression). An inadequate secretion of GCs from the adrenal gland, in relation to stress and inflammation, seems to play an important role in the pathogenesis and disease progression of RA. At present there is clear evidence that GC therapy, especially long-term low-dose treatment, slows radiographic progression by at least 50% when given to patients with early RA, hence satisfying the conventional definition of a DMARD. In addition, long-term follow-up studies suggest that RA treatment strategies which include GC therapy may favorably alter the disease course even after their discontinuation. Finally, a low-dose, modified night-release formulation of prednisone, although administered in the evening (replacement therapy), has been developed to counteract the circadian (night) rise in proinflammatory cytokine levels that contributes to disease activity, and might represent the way to further optimize the DMARD activity exerted by GCs in RA.
24127184 Treatment with anti–tumor necrosis factor biologic agents in human T lymphotropic virus 2014 May OBJECTIVE: To investigate the response to and safety of anti–tumor necrosis factor (anti-TNF) therapy in human T lymphotropic virus type I (HTLV-I)–positive patients with rheumatoid arthritis (RA). METHODS: Therapeutic response was evaluated in 10 HTLV-I–positive and 20 HTLV-I–negative patients with RA (sex and age matched) at 3 months after the beginning of anti-TNF therapy using the European League Against Rheumatism improvement criteria. As secondary end points, the discontinuation rate of anti-TNF therapy and its safety, especially the development of adult T cell leukemia (ATL), were evaluated over a 2-year period. RESULTS: Significantly higher baseline levels of C-reactive protein (CRP) were observed in HTLV-I–positive patients than in HTLV-I–negative patients (P = 0.0003). The response rate to anti-TNF therapy was lower in HTLV-I–positive patients than in HTLV-I–negative patients. The median CRP level, erythrocyte sedimentation rate, and Disease Activity Score in 28 joints at 3 months after anti-TNF treatment in HTLV-I–positive patients were significantly higher than in HTLV-I– negative patients (P = 0.003, P = 0.03, and P = 0.003, respectively). The discontinuation rate due to insufficient response was significantly higher in HTLV-I–positive patients than in HTLV-I–negative patients (P = 0.013). During the 2-year observation period, no patients developed ATL. CONCLUSION: These data suggest that HTLV-I–positive patients with RA had higher inflammation and greater resistance to anti-TNF treatment than HTLV-I–negative patients. Further study is necessary to determine whether HTLV-I infection should be measured when anti-TNF agents are administered to patients with RA, especially in areas were HTLV-I is endemic.
23489410 Dosing patterns of three tumor necrosis factor blockers among patients with rheumatoid art 2013 May OBJECTIVE: To describe dosing patterns of etanercept, adalimumab, and infliximab in rheumatoid arthritis (RA) patients in US managed care. METHODS: This retrospective analysis included adult (18-64 years) RA patients in the HealthCore Integrated Research Database with ≥ 1 claim for etanercept, adalimumab, or infliximab between 7/1/2007 and 1/31/2010. Patients had 6 months pre-index and 12 months post-index claim eligibility. Patients without any TNF blocker claim during the pre-index period were considered new patients and patients with a TNF blocker claim during the pre-index period were considered continuing patients. Persistence, discontinuation, switch, and dose escalation patterns were evaluated. Patients with 1-year persistence were evaluated for dose escalation using two methods: (1) average weekly dose and (2) increase from 50 mg to 75 mg or 100 mg weekly of etanercept or from 40 mg every other week to 40 mg weekly of adalimumab or increase in vial or decreased infusion interval for infliximab. RESULTS: Data from 2426 patients were analyzed (1595 etanercept; 417 adalimumab; 414 infliximab). Persistence ≥ 1 year on index medication was reported in 62.2% and 89.2% of new and continuing patients on etanercept, respectively, 66.0% and 94.0% on adalimumab, and 68.9% and 96.4% on infliximab. Discontinuation occurred in 19.7% and 7.9% of new and continuing patients on etanercept, respectively, 20.6% and 4.5% on adalimumab, and 18.8% and 2.1% on infliximab. Switching occurred in 12.2% and 4.3% of new and continuing patients on etanercept, respectively, 9.1% and 1.8% on adalimumab, and 10.4% and 2.1% on infliximab. Dose escalation was lower with etanercept (0.4-2.6%) than adalimumab (12.6-24.3%) or infliximab (40.0-79.5%) (P < 0.0001). CONCLUSIONS: Discontinuation and switching were common within 1 year of initiating etanercept, adalimumab, and infliximab in patients with RA in this analysis. Study limitations included the restricted patient age range; analysis of three TNF blockers; study period (prior to approval of additional agents); and missing reasons for treatment changes.
25430993 The pathogenic Th profile of human activated memory Th cells in early rheumatoid arthritis 2015 Apr Our aim is to study the behavior of memory Th cells (Th17, Th17/1, and Th1 profiles) from early rheumatoid arthritis (eRA) patients after their in vitro activation/expansion to provide information about its contribution to RA chronicity. Moreover, we analyzed the potential involvement of vasoactive intestinal peptide (VIP) as an endogenous healing mediator. CD4(+)CD45RO(+) T cells from PBMCs of HD and eRA were activated/expanded in vitro in the presence/absence of VIP. FACS, ELISA, RT-PCR, and immunocytochemistry analyses were performed. An increase in CCR6(+)/RORC(+) cells and in RORC-proliferating cells and a decrease in T-bet-proliferating cells and T-bet(+)/RORC(+) cells were shown in eRA. mRNA expression of IL-17, IL-2, RORC, RORA, STAT3, and Tbx21 and protein secretion of IL-17, IFNγ, and GM-CSF were higher in eRA. VIP decreased the mRNA expression of IL-22, IL-2, STAT3, Tbx21, IL-12Rβ2, IL-23R, and IL-21R in HD and it decreased IL-21, IL-2, and STAT3 in eRA. VIP decreased IL-22 and GM-CSF secretion and increased IL-9 secretion in HD and it decreased IL-21 secretion in eRA. VPAC2/VPAC1 ratio expression was increased in eRA. All in all, memory Th cells from eRA patients show a greater proportion of Th17 cells with a pathogenic Th17 and Th17/1 profile compared to HD. VIP is able to modulate the pathogenic profile, mostly in HD. Our results are promising for therapy in the early stages of RA because they suggest that targeting molecules involved in the pathogenic Th17, Th17/1, and Th1 phenotypes and targeting VIP receptors could have a therapeutic effect modulating these subsets. KEY MESSAGES: Th17 cells are more important than Th1 in the contribution to pathogenesis in eRA patients. Pathogenic Th17 and Th17/1 profile are abundant in activated/expanded memory Th cells from eRA patients. VIP decreases the pathogenic Th17, Th1, and Th17/1 profiles, mainly in healthy donors. The expression of VIP receptors is reduced in eRA patients respect to healthy donors, whereas the ratio of VPAC2/VPAC1 expression is higher.
23379516 Changes in chemokines and their receptors in blood during treatment with the TNF inhibitor 2013 OBJECTIVES: Chemokines are involved in leucocyte recruitment into inflammatory sites. The release of certain chemokines is augmented by tumour necrosis factor (TNF). Infliximab, a monoclonal antibody that blocks the effects of TNF, is used for treatment of rheumatoid arthritis (RA). The effect of TNF blockage on chemokines is not fully understood. The aim of this study was to analyse the effects on chemokines and their receptors on peripheral mononuclear cells of anti-TNF treatment in RA patients. METHOD: Twelve patients with established RA who started treatment with infliximab and nine patients with early RA treated with other anti-rheumatic drugs were followed clinically for 30 weeks and chemokine levels in blood samples were analysed along with chemokine receptor expression on the surface of T cells and monocytes. Nine healthy subjects were included as a control group. RESULTS: The chemokine CXCL10/IP-10 was significantly higher in RA patients than in healthy controls (p = 0.012). Two weeks after infliximab infusion, CXCL10/IP-10, CCL2/MCP-1, and CCL4/MIP-1β had decreased significantly (p = 0.005, 0.037, and 0.028, respectively), and after 30 weeks of treatment, soluble CD26 was significantly increased (p = 0.050). Several chemokine receptors on T cells were elevated in RA patients at inclusion. The expression of CCR2 and CXCR1 on T cells decreased significantly after infliximab treatment. CONCLUSIONS: The chemokines CXCL10/IP-10, CCL2/MCP-1, and CCL4/MIP-1β, mainly targeting the T-helper (Th)1 immune response, decreased after treatment with anti-TNF, suggesting a more pronounced effect on Th1 activity than on Th2-mediated response. Several chemokine receptors on blood T cells were elevated in RA patients, suggesting that they may be involved in the recruitment of T lymphocytes from the blood to affected tissues.
22807272 Racial/ethnic differences in the use of biologic disease-modifying antirheumatic drugs amo 2013 Feb OBJECTIVE: To assess racial/ethnic differences in the use of biologic disease-modifying antirheumatic drugs (DMARDs) among California Medicaid (Medi-Cal) rheumatoid arthritis (RA) patients. METHODS: Medi-Cal patient level data for 5,385 DMARD recipients between ages 18 and 100 years with at least 1 diagnosis of RA (International Classification of Disease, Ninth Revision, Clinical Modification code 714.xx) and the use of 1 DMARD between January 1, 1998 and December 31, 2005 were collected. The outcome of interest was the choice of either standard DMARDs (methotrexate, lefluonomide, hydroxychloroquine, and sulfasalazine) or biologic DMARDs (adalimumab, etanercept, anakinra, and infliximab). A univariate analysis and logistic regression model were applied to examine the association of the choice of DMARD among different racial/ethnic groups. RESULTS: In the univariate analysis, biologic DMARD use was significantly associated with race/ethnicity (P < 0.001). In the multivariate logistic regression model, after adjusting for age, sex, insurance coverage, 12 comorbid conditions, RA-related drug prescription, RA-related inpatient stay, and rehabilitation visits, African Americans had 53% lower odds of receiving biologic DMARDs as compared to whites, whereas Hispanics had 36% increased odds of receiving biologic DMARDs as compared to whites. CONCLUSION: In this Medi-Cal population, with its racial diversity and relatively homogenous socioeconomic status and health care benefits, racial/ethnic differences were found in RA patients receiving biologic DMARDs.
22854883 Ethnic differences in the prognostic utility of rheumatoid factor isotypes and anticyclic 2013 Jul OBJECTIVES: The prognostic significance of rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) in rheumatoid arthritis (RA) remains contentious due to the conflicting lines of evidence. This study aims to determine the association between RF isotypes and anti-CCP with disease severity in RA patients from three ethnic groups. METHODS: A total of 147 RA patients from three different ethnic groups (Malays, Chinese, and Indians) who fulfilled the 1987 American College of Rheumatology (ACR) revised criteria for RA were recruited into this study. The seroprevalence of RF isotypes immunoglobulin (Ig)A, IgG, and IgM, as well as anti-CCP was determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. Multinomial regression analysis was performed to assess the independent effects of autoantibody status on the development of deforming and erosive RA and the presence of extra-articular manifestations (EAM). RESULTS: In Chinese patients, we found a significant association (p < 0.05) between IgG RF and anti-CCP and the presence of erosive disease, as well as IgM RF and IgG RF with the presence of joint deformities. In Indian patients, IgM RF was associated with deforming disease, whereas none of the antibodies were associated with disease severity in Malay patients. Multinomial regression analysis revealed that IgG RF was the most important predictor variable for erosive disease in Chinese patients, and IgM RF the only predictor variable associated with deforming disease in both Chinese and Indian RA patients. CONCLUSIONS: There is variability in the phenotypic association of RF isotypes and anti-CCP in relation to disease severity of RA in the three ethnic groups. RF, in particular, IgG and IgM, may be better prognosticators of severe disease in Chinese and Indian patients.
23394902 Influence of interleukin-4 gene polymorphisms and interleukin-4 serum level on susceptibil 2013 Mar BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which interleukin-4 (IL-4) plays an important role. This study aimed to investigate the influence of IL-4 variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms on RA susceptibility, activity and severity in Egyptian population. MATERIALS AND METHODS: One hundred and seventy-two RA patients and 172 controls were enrolled in this study. IL-4 VNTR and IL-4-590 promoter polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum IL-4 and anti-cyclic citrullinated peptides (anti-CCPs) antibody concentrations were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Subjects with IL-4-590 TT genotype were significantly more likely to develop RA. IL-4 VNTR 1/1 genotype, IL-4-590 TT and CT genotypes were significantly more associated with erosive RA and positive anti-CCP antibody. RA severity parameters were significantly increased, while, IL-4 level was significantly decreased in RA patients with IL-4 VNTR 1/1 and IL-4-590 TT genotypes. Only patients with IL-4-590 TT genotype showed a significant increase of all RA activity parameters. CONCLUSION: IL-4 VNTR and IL-4-590 promoter polymorphisms may be helpful for assessing RA severity in Egyptian population. Moreover, IL-4-590 promoter polymorphism may be associated with increased risk and activity of RA.
23337264 Therapeutic potential of tumour necrosis factor-alpha antagonists in patients with chronic 2013 May OBJECTIVES: Elevated levels of tumour necrosis factor alpha (TNF-alpha) are associated with the development of heart failure. TNF-alpha antagonists, etanercept (ETA) and infliximab (INF) have been used for treating different clinical conditions. Anti-TNF-alpha therapy did not show favourable results in patients with chronic heart failure (CHF). This review analyses the reasons for anti-TNF-alpha therapy failure in CHF patients; potential approaches for improved clinical outcome are also addressed. DESIGN AND METHODS: Data analysis from clinical trials of CHF patients treated with ETA and INF. RESULTS: In heart failure patients, ETA and INF therapy did not lead to improved clinical outcomes and high doses of INF were associated with worsening of cardiac events. This contrasts with the observation that these agents are associated with reduced cardiac events when used in patients with inflammatory diseases such as rheumatoid arthritis (RA). CONCLUSIONS: Treatment of CHF patients with TNF-alpha antagonists did not show encouraging results. There is a need for the development of better treatment strategies for CHF. Perhaps, tailored anti-TNF-alpha therapy in relation to the TNF-alpha genotype of CHF patients and targeting of the cytokine gene expression via signalling pathway inhibitors may have useful clinical implications.
24929634 Prevalence of ultrasound-detected residual synovitis and risk of relapse and structural pr 2014 Nov OBJECTIVES: The aims of this study were to assess the prevalence of US-detected residual synovitis in patients with RA in clinical remission (CR) and evaluate its predictive value for relapse and structural progression. METHODS: We performed a systematic literature search of Medline, Embase and rheumatology meeting databases from 1 January 2001 to 28 May 2012. The prevalence of US grey-scale (USGS) signals (synovial hypertrophy or joint effusion) and power Doppler (PD) signals were collected, taking into account CR definitions [44-joint DAS (DAS44), 28-joint DAS (DAS28), SDAI, ACR 1981 or ACR/European League Against Rheumatism 2011], stage of RA (early or long-standing) and US examination (from 5 to 44 joints assessed). A meta-analysis assessing the risk of relapse or structural progression in patients with synovitis involved the Mantel-Haenszel method. RESULTS: We included 19 studies of 1618 patients, 1369 in remission. The prevalence of USGS positive (USGS+), USGS+/PD negative (PD-), USGS+/PD positive (PD+) and USGS negative (USGS-/PD- was 84%, 41%, 44% and 15%, respectively. The prevalence of USGS+ or USGS+/PD+ was comparable among CR definitions and US methods. The prevalence of USGS+ and USGS+/PD+ was greater for long-standing than early RA (P < 0.001). Meta-analyses of five studies (271 patients), three studies (173 patients) and two studies (798 joints) revealed an association of USGS+/PD+ and risk of relapse [odds ratio (OR) 3.2 (95% CI 1.8, 5.9), P = 0.0001, I(2) = 0%] and structural progression in individual patients [OR 9.13 (95% CI 1.1, 74.3), P = 0.04, I(2) = 43%] and joints [OR 6.95 (95% CI 3.4, 13.9), P < 0.0001, I(2) = 6%] over 1-2 years. CONCLUSION: US-detected residual synovitis is frequent and predicts the risk of relapse and structural progression in RA patients with CR.
24098547 Graphical tools for network meta-analysis in STATA. 2013 Network meta-analysis synthesizes direct and indirect evidence in a network of trials that compare multiple interventions and has the potential to rank the competing treatments according to the studied outcome. Despite its usefulness network meta-analysis is often criticized for its complexity and for being accessible only to researchers with strong statistical and computational skills. The evaluation of the underlying model assumptions, the statistical technicalities and presentation of the results in a concise and understandable way are all challenging aspects in the network meta-analysis methodology. In this paper we aim to make the methodology accessible to non-statisticians by presenting and explaining a series of graphical tools via worked examples. To this end, we provide a set of STATA routines that can be easily employed to present the evidence base, evaluate the assumptions, fit the network meta-analysis model and interpret its results.
23538191 Patient preferences for biologic agents in rheumatoid arthritis: a discrete-choice experim 2013 Mar OBJECTIVES: To assess patients' preferences for rheumatoid-arthritis treatments with biologic agents using a discrete-choice experiment. METHODS: A discrete-choice experiment was conducted with adult rheumatoid-arthritis patients who had never been treated with biological agents from two university hospitals-public and private-in Buenos Aires, Argentina. We evaluated preferences for seven treatment attributes (with two to three levels each): effectiveness, mode of administration, frequency of administration, local and systemic adverse events, severe infections, and out-of-pocket costs.A probit regression model was used to analyze the relative importance of rheumatoid-arthritis treatment attributes. We estimated attributes' relative importance and their 95% confidence intervals. RESULTS: Survey responses from 240 patients with rheumatoid arthritis receiving conventional disease-modifying antirheumatic drugs were included in the study. All tested biological agents' attributes significantly affected the choice of treatment. Attributes' relative importance in decreasing order was the following (mean, confidence interval 95%): cost, 0.81 (0.69-0.92); systemic adverse events, 0.66 (0.57-0.76); frequency of administration, 0.61 (0.52-0.71); efficacy, 0.42 (0.32-0.51); route of administration, 0.41 (0.30-0.52); local adverse events, 0.40 (0.31-0.49); and serious infections, 0.29 (0.22-0.37). CONCLUSIONS: Different treatment attributes had a significant and different influence in rheumatoid-arthritis patients' choice of biological agents. This type of study can not only inform about patients' preferences but also about the trade-offs among different possible treatments or process-related attributes.
25274893 The effect of antiestrogen agents on risk of autoimmune disorders in patients with breast 2015 Jan OBJECTIVE: To investigate the relationship between antiestrogen therapy in women with breast cancer and risk of autoimmune disease. METHODS: We used a national database to assess the incidence of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) following treatment with selective estrogen receptor modulators (SERM) or aromatase inhibitors (AI) in women with breast cancer. The total number of patients in our study was 190,620. RESULTS: We observed highly significant, cumulative dose-dependent increased OR of incidence of both SLE and RA following treatment with SERM (p < 0.0001). The odds of developing RA were also increased following AI therapy (p < 0.001), but there was a trend for reduced odds of SLE, though this trend did not attain statistical significance (p = 0.070 for 2-11 months of treatment and p = 0.254 for 12+ months of treatment). CONCLUSION: Antiestrogen agents may have an important effect on risk of autoimmune disease.