Rheumatoid arthritis (RA) is a heterogeneous disease characterized by a variable course of remissions and relapses. Single measures of disease activity at only one point in time may not reflect the overall control of disease activity.
The aim was to determine (i) the predictive value of 20 baseline demographic and disease variables on mortality, and (ii) the relationship between serial measures of the Stoke index (SI; a validated index of disease activity in RA) and mortality in RA.
Mortality in 309 RA patients followed up for a median of 14 yr was analysed retrospectively. The standardized mortality ratio (SMR) was calculated for all causes of death. The predictive values of baseline and time-integrated variables were assessed using multivariate Cox proportional hazards regression analysis.
The SMR was 1.65. At baseline, only nodules, erosions, RA latex titre, white cell count and globulin level were predictive of mortality after correction for age, sex and disease duration. Using a stepwise Cox proportional hazards regression model, the most powerful predictors of mortality were age, nodules and RA latex titre. Individual measures of disease activity and the SI at baseline were not predictive of mortality. However, the mean level of the SI over 12 months was related to mortality (P=0.039).
At baseline, the demographic and disease variables most significantly related to mortality in RA are age, nodules and RA latex titre. Individual measures of disease activity at a single point in time are poor predictors of mortality in RA. However, measurement of the mean level of disease activity over time using the composite SI has a significant relationship with mortality. A high level of sustained inflammation appears to be an important predictor of premature death.
"Markers of inflammation such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and soluble tumour necrosis factor receptors have been shown to be predictive of mortality in RA [2,3,5,7-9,13], but many other markers associated with the disease process have not been investigated. Some of these may provide alternative or better predictors of early mortality. "
[Show abstract][Hide abstract] ABSTRACT: Introduction
Matrix metalloproteinases (MMPs) are implicated in the destruction of the joint and have been shown to be strongly associated with inflammation in rheumatoid arthritis (RA). Circulating MMPs have also been associated with cardiovascular disease in the general population, and are predictive of cardiovascular mortality. The purpose of the present study was to determine whether circulating levels of MMPs are predictive of mortality in RA.
A multiplex suspension array system (Luminex®) was used to measure levels of MMPs (1, 2, 3, 8 and 9) in sera taken at recruitment of RA patients (n = 487) in a study of factors associated with mortality in RA. Patients were tracked on the National Health Service Central Register for notification of death, and the relationship between baseline MMP levels and mortality was analysed using Cox proportional hazards regression analysis.
At the time of follow-up, 204/486 patients had died, of which 94 (46.1%) had died of circulatory diseases, 49 of malignancy (24.0%), and 42 (20.6%) of respiratory diseases. In a stepwise analysis which included all MMPs, only MMP-8 was significantly associated with all cause mortality (P = 0.0007, 0.6% hazard ratio increase per ng/ml). No association was found between MMP levels and mortality due to circulatory disease or malignancy. However MMP-8 levels were strongly associated with mortality due to respiratory disease (P < 0.0001, 1.3% hazard ratio increase per ng/ml). The association with respiratory disease related mortality remained highly significant in multivariate models which included smoking as well as markers of severity and disease activity such as rheumatoid factor, nodular disease, and C-reactive protein (CRP).
The serum level of MMP-8 is a strong predictor of mortality in RA, especially that due to respiratory disease. This finding is consistent with increased activation of neutrophils in RA and identifies serum MMP-8 as a useful marker for increased risk of premature death.
"Rheumatoid arthritis (RA) is a common chronic autoimmune inflammatory disease characterized by destruction of the synovial joints, leading to progressive disability, increased co-morbidity and premature mortality , . Both genetic and environmental factors are known to contribute to the development of the disease . "
[Show abstract][Hide abstract] ABSTRACT: Rheumatoid Arthritis (RA) is a chronic immune mediated disease associated with deregulation of many cell types. It has been reported that different T cell subsets have opposite effects in disease pathogenesis, in particular Th17 and Treg cells.
We investigated whether non-depleting anti-CD4 monoclonal antibodies, which have been reported as pro-tolerogenic, can lead to protection from chronic autoimmune arthritis in SKG mice--a recently described animal model of RA--by influencing the Th17/Treg balance. We found that non-depleting anti-CD4 prevented the onset of chronic autoimmune arthritis in SKG mice. Moreover, treated mice were protected from the induction of arthritis up to 60 days following anti-CD4 treatment, while remaining able to mount CD4-dependent immune responses to unrelated antigens. The antibody treatment also prevented disease progression in arthritic mice, although without leading to remission. Protection from arthritis was associated with an increased ratio of Foxp3, and decreased IL-17 producing T cells in the synovia. In vitro assays under Th17-polarizing conditions showed CD4-blockade prevents Th17 polarization, while favoring Foxp3 induction.
Non-depleting anti-CD4 can therefore induce long-term protection from chronic autoimmune arthritis in SKG mice through reciprocal changes in the frequency of Treg and Th17 cells in peripheral tissues, thus shifting the balance towards immune tolerance.
PLoS ONE 05/2010; 5(5):e10558. DOI:10.1371/journal.pone.0010558 · 3.23 Impact Factor
"The HAQ, for example, can be quite abnormal in individuals with little apparent functional loss, and can be normal in individuals with substantial and obvious dysfunction . Because of the problems in ascertaining a latent outcome, researchers often preferentially measure observed outcomes such as work disability [6-10], joint replacement surgery , income , or death [13-16]. Yet these outcomes also have their problems because they often take too long to occur, because they may not apply to all patients, and because they do not touch on the day-to-day substance of RA. "
[Show abstract][Hide abstract] ABSTRACT: Although functional outcome is frequently discussed and written about, it is often not clear what functional outcome is and how it can be measured. This paper introduces the concept of latent and observed measures of functional disability, and distinguishes between disability as a process measure and disability as an outcome measure. Using the Health Assessment Questionnaire as the main functional outcome measure in rheumatoid arthritis, we propose and discuss several methods for determining disability, and describe the implications of altering the disability course.
Arthritis research 02/2002; 4 Suppl 2(Suppl 2):S11-5. DOI:10.1186/ar547
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