Search

Patients with rheumatoid arthritis (RA) who experience treatment failure with one anti–tumor necrosis factor (anti‐TNF) agent, due to either inefficacy or toxicity, are frequently switched to a second anti‐TNF agent, although the benefits of switching are unknown. The present study was undertaken to compare drug continuation rates between the first course and second course of anti‐TNF therapy.The study involved a prospective cohort of RA patients from a UK national register of new anti‐TNF treatment starts (n = 6,739; 876 starting adalimumab, 2,826 starting etanercept, and starting 3,037 infliximab). Over a mean 15 months of followup, 841 patients stopped taking the first drug due to inefficacy and 1,023 stopped the first drug due to toxicity, of whom 503 and 353, respectively, were switched to a second anti‐TNF agent. Kaplan‐Meier survival curves were plotted to determine continuation rates for each course, and Cox regression was used to compare each course for the risk of stopping and the reason for stopping (inefficacy or toxicity).Overall, 73% of patients who switched to a second anti‐TNF agent remained on the new therapy by the end of followup. First drug discontinuation due to inefficacy was associated with an increased rate of second drug discontinuation due to inefficacy (hazard ratio [HR] 2.7, 95% confidence interval [95% CI] 2.1–3.4) but not toxicity (HR 1.1, 95% CI 0.9–1.5). Similarly, first drug discontinuation due to toxicity was associated with an increased rate of second drug discontinuation due to toxicity (HR 2.3, 95% CI 1.9–2.9) but not inefficacy (HR 1.2, 95% CI 0.8–1.6).RA patients who are switched to a second anti‐TNF drug have high rates of continuation, although among those who must discontinue treatment, the reasons for stopping a second drug are related to the reasons for stopping the first drug. This large data set from the UK provides the first estimates of the magnitude of these effects in patients with long‐standing severe RA. [ABSTRACT FROM AUTHOR]

The American College of Rheumatology (ACR) 1987 criteria for rheumatoid arthritis (RA) can be applied in 2 formats, a standard “x/y” list and a decision tree. This study evaluated the performance of the decision tree compared with the list approach in the ascertainment of RA in subjects with new‐onset inflammatory polyarthritis (IP) over the first 5 years of observation. Moreover, the use of clinical surrogates to substitute for missing rheumatoid factor (RF) and radiologic erosion data was assessed for validity and for its influence on the resulting RA prevalence estimates.In this population‐based prospective study, 848 subjects with new‐onset IP were interviewed and examined at baseline, with followup at 1, 2, 3, and 5 years. RF and erosion status were determined at prespecified time points. The list criteria were applied cumulatively, while the decision tree was applied cross‐sectionally using either data surrogates or the actual reported data. RA prevalence in the 848 subjects and agreement in classification between the 2 methods was assessed at each time point. The influence of using clinical surrogates on RA prevalence estimates at 5 years and the agreement between surrogate and real results were also analyzed.At baseline, RA prevalence was higher using the decision tree compared with the list approach (63% versus 47%; P = 0.0001); by 5 years of followup, RA estimates were approximately equal (69% versus 72%) and agreement between the approaches was good (κ = 0.67). The use of surrogates had little influence on RA prevalence at 5 years, although substitution of metacarpophalangeal joint swelling for erosion produced a higher RA prevalence estimate (78% versus 70%). Although there was only weak agreement between surrogate and real data, the use of the surrogate data provided good to very good agreement between the approaches in categorizing subjects as RA positive (κ = 0.61–0.72).Over 5 years, the 2 formats of the ACR criteria for RA performed similarly, with no important differences between them. The use of surrogates for missing radiologic and serologic data did not have any major influence on disease classification. Although the RA criteria were not originally derived from subjects with early disease in a population setting, this study shows that the use of the decision tree approach with the option of substituting clinical surrogates for missing laboratory data is an appropriate alternative to the conventional list approach. [ABSTRACT FROM AUTHOR]

A number of covariate-balancing methods, based on the propensity score, are widely used to estimate treatment effects in observational studies. If the treatment effect varies with the propensity score, however, different methods can give very different answers. The authors illustrate this effect by using data from a United Kingdom–based registry of subjects treated with anti–tumor necrosis factor drugs for rheumatoid arthritis. Estimates of the effect of these drugs on mortality varied from a relative risk of 0.4 (95% confidence interval: 0.16, 0.91) to a relative risk of 1.3 (95% confidence interval: 0.8, 2.25), depending on the balancing method chosen. The authors show that these differences were due to a combination of an interaction between propensity score and treatment effect and to differences in weighting subjects with different propensity scores. Thus, the methods are being used to calculate average treatment effects in populations with very different distributions of effect-modifying variables, resulting in different overall estimates. This phenomenon highlights the importance of careful selection of the covariate-balancing method so that the overall estimate has a meaningful interpretation. [ABSTRACT FROM AUTHOR]

To investigate the association of red meat and other specific dietary components in predicting the development of inflammatory polyarthritis. This nested case–control study was conducted within a prospective population‐based study of cancer incidence (European Prospective Investigation of Cancer in Norfolk [EPIC‐Norfolk]). EPIC‐Norfolk recruited 25,630 subjects ages 45–75 years between 1993 and 1997. Dietary intake was assessed at baseline using a 7‐day food diary, and the information was analyzed using dietary analysis software. Patients with new cases of inflammatory polyarthritis were identified by linkage with the Norfolk Arthritis Register, a primary care–based inception study of inflammatory polyarthritis, and were matched for age and sex to 2 controls from EPIC‐Norfolk. The risk for development of inflammatory polyarthritis was compared between subjects in the highest and lowest tertiles of dietary intake using conditional logistic regression and was expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). Between 1993 and 2002, 88 new patients with inflammatory polyarthritis were identified and matched with 176 controls. Among patients, the level of red meat intake was higher (P = 0.04) and that of vitamin C was lower (P = 0.03) compared with intake among controls, but no difference in total energy intake was observed. Patients were more likely to be smokers. After adjusting for total energy intake, smoking, and other possible dietary confounders, subjects with the highest level of consumption of red meat (OR 1.9, 95% CI 0.9–4.0), meat and meat products combined (OR 2.3, 95% CI 1.1–4.9), and total protein (OR 2.9, 95% CI 1.1–7.5) were at an increased risk for inflammatory polyarthritis. A high level of red meat consumption may represent a novel risk factor for inflammatory arthritis or may act as a marker for a group of persons with an increased risk from other lifestyle causes. [ABSTRACT FROM AUTHOR]

Abstract This study was undertaken to determine the degree of interaction between hormonal and athletic effects on changes in bone mineral density (BMD, g/cm2) with time in women around the menopause. Thirty-five elite female runners aged over 40 participated in a longitudinal cohort study of hip and spine bone density changes and had two measurements a mean of 4.1 years apart. Eighteen remained estrogenized throughout the study (E+ to +), ten remained postmenopausal throughout (E- to -), while seven showed a change in status (E- to +) or (E+ to -). At study exit, both postmenopausal E+ and E- subjects had significantly higher than expected broadband ultrasound attenuation (BUA) and velocity of sound (VOS) values at the calcaneus. However, Z-score 95% confidence intervals for BMD of the hip and spine embraced zero except at the femoral trochanter in E+ women. The E+ to + group did not lose bone at any site. The E- to - group lost bone significantly, but only at the femoral neck and spine at rates close to 1% annually. Multiple analysis of variance repeated measures analysis showed a significant interaction in the effects of estrogen exposure with DXA measurement site, with the femoral trochanter being less affected by E- status than the spine and femoral neck. Body mass index (BMI: weight/height2, kg/m2) had a significantly positive effect on total hip and femoral neck BMD independently of estrogen status. In conclusion, in this pilot study, postmenopausal elite runners not on hormone replacement therapy lost BMD from the femoral neck and spine at the expected rates but in the femoral trochanter bone loss appeared reduced and in the calcaneus BUA and VOS were maintained close to young normal values. [ABSTRACT FROM AUTHOR]

To test the hypothesis that the C‐reactive protein (CRP) concentration at baseline is an independent predictor of death from cardiovascular disease (CVD) in newly diagnosed patients with inflammatory polyarthritis (IP).Patients with IP (n = 506) who were recruited from the Norfolk Arthritis Register between 1990 and 1992 were followed up to the end of 2001, and complete data on mortality were obtained. At baseline, subjects underwent a structured interview and joint examination and completed a Health Assessment Questionnaire (HAQ). Blood was obtained and analyzed for rheumatoid factor (RF) and CRP concentration. Cox regression was used to calculate hazards ratios (HRs) for risk of death from CVD.The median followup was 10.1 years (interquartile range 9.3–10.8). There were 104 deaths, 40 of which were the result of CVD. Elevated CRP levels (≥5 mg/liter) predicted death from CVD in univariate analyses: HR 3.9 (95% confidence interval [95% CI] 1.2–13.4) for men, and HR 4.22 (95% CI 1.4–12.6) for women. After adjusting for age and sex, the CVD mortality association was strongest in the subgroup of patients who were RF positive at baseline (adjusted HR 7.4 [95% CI 1.7–32.2]). Multivariate analysis revealed that elevated CRP levels remained a significant independent predictor of death from CVD, even after adjusting for age, sex, smoking status, HAQ score, RF positivity, and swollen joint counts (HR 3.3 [95% CI 1.4–7.6]).The CRP concentration at baseline is an important predictor of subsequent death from CVD in patients with new‐onset IP and is independent of other indicators of disease severity. This supports the theory that CRP may play a direct role in the pathogenesis of CVD. [ABSTRACT FROM AUTHOR]

To establish linkage and replicate the association of macrophage migration inhibitory factor (MIF) with juvenile idiopathic arthritis (JIA). Three hundred twenty-one Caucasian simplex families from the UK were genotyped for polymorphisms of MIF using SNaPshot ddNTP primer extension, or by a fluorescently labeled primer method, and capillary gel electrophoresis. The functional significance of the promoter polymorphisms was studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines. MIF was linked and associated with JIA (P = 0.0016). Specifically, a 2-point promoter haplotype, CATT7–MIF-173*C, was found to be transmitted in excess (38 transmitted: 21 not transmitted) in the JIA patients. Conditional extended transmission disequilibrium test and pairwise extended transmission disequilibrium test predicted functional interaction between the 2 polymorphic positions. The interaction of the CATT repeat with MIF-173*G/C was found to be specific to the cell type. Replication of an association and linkage of MIF with JIA has been established. Functional interaction between the polymorphic positions on the linked haplotype has also been shown. The molecular mechanism of this interaction is currently being investigated. [ABSTRACT FROM AUTHOR]

To address the functional and prognostic relevance of the -173 single-nucleotide G-to-C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease. A total of 136 patients with systemic-onset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group''s National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF-173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme-linked immunosorbent assay. The evaluation of the association of the MIF-173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ); and 3) data concerning the treatment regimens during the disease course. Systemic-onset JIA patients carrying a MIF-173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF-173*C allele than in MIF-173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF-173*C allele. At the last visit, the numbers of joints with active arthritis, the C-HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF-173*C allele. Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA. [ABSTRACT FROM AUTHOR]