Radiographic Progression In Rheumatoid Arthritis Research Articles

Pharmacogenetics of therapies in rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory, aggressive arthritis causing irreversible joint destruction and damage when left untreated. Disease-modifying antirheumatic drugs (DMARDs) are the mainstay of treatment for RA and ameliorate not only the clinical signs and symptoms but also joint damage associated with the disease. In recent years, biological therapies have been introduced for the treatment of RA, and the effectiveness of these agents in slowing the clinical and radiographic progression in RA has been established beyond question. However, there is significant variability in the response of patients with RA to these therapies. Moreover, the biological therapies are expensive, totaling several thousand dollars in yearly patient costs. Pharmacogenomics, the study of genetic variations in drug-metabolizing enzymes and their translation to differential responses to drugs, is a nascent but rapidly evolving field. The application of pharmacogenomics to therapies used in RA, particularly the new expensive biological agents, holds great promise for tailoring therapy with these agents based on a patient's genetics. Published literature on the pharmacogenetics of commonly used DMARDs and the emerging body of literature on the pharmacogenetics of the new biological therapies in RA are the focus of this review. As evident from the contents of this review, pharmacogenomics is an exciting field which is progressing productively and rapidly. Pharmacogenomic approaches offer powerful tools to optimize drug therapy in individual patients.

Association between stromal cell–derived factor 1 chemokine gene variant and radiographic progression of rheumatoid arthritis

Association between stromal cell–derived factor 1 chemokine gene variant and radiographic progression of rheumatoid arthritis

Prediction of radiographic progression in early rheumatoid arthritis (RA) using time-integrated C-reactive protein (TICRP): a population-based approach

AIMS Various rheumatic diseases, including RA, are known to be associated with elevated levels of acute-phase proteins, particularly CRP. Studies suggest that there is a significant correlation between elevated CRP level and increased radiographic progression. The purpose of this analysis was to develop a population model to predict radiographic progression using TICRP. METHODS: Both CRP and Total Sharp Score (TSS) data were collected for up to 24 months in 560 patients with early RA (183: 25 mg etanercept twice weekly (biw); 184: 10 mg etanercept biw; 193: methotrexate once weekly) in a clinical study. A Freundlich model was used to depict the relationship between CRP and TSS using NONMEM. The potential impact of covariates, including treatment, sex, age, baseline TSS, baseline CRP, baseline erosion, and baseline joint-space narrowing, on model parameters (Freundlich exponent constant [1/N], Freundlich constant [K]) was assessed. RESULTS: The population model demonstrated that TICRP predicts the radiographic progression of RA quantitated by TSS. The model's predictive performance was confirmed by 8000 bootstrapping runs. The typical (SE) model parameters were 7.82 (1.35) for K and 0.77 (0.06) for 1/N. No important covariates were identified. CONCLUSIONS: Radiographic progression in RA can be successfully predicted by TICRP using a population-based approach. The utility of this model needs further investigation. Clinical Pharmacology & Therapeutics (2004) 75, P53–P53; doi: 10.1016/j.clpt.2003.11.202

Evidence from clinical trials and long-term observational studies that disease-modifying anti-rheumatic drugs slow radiographic progression in rheumatoid arthritis: updating a 1983 review.

Earlier reports, including a comprehensive 1983 review, had indicated that slowing of radiographic progression was relatively unusual in treatment of rheumatoid arthritis (RA) using traditional disease modifying anti-rheumatic drugs. However, in recent years, slowing of radiographic progression has been documented in a number of clinical trials, as well as long-term observational studies, with use of (in alphabetical order) adalimumab, anakinra, corticosteroids, cyclophosphamide, cyclosporin, etanercept, gold salts, infliximab, leflunomide, methotrexate and sulphasalazine. At this time, disease modification is a realistic goal in the clinical care of patients with RA. Documentation of improved long-term outcomes requires long-term observational data over 5-20 yr to supplement data from randomized controlled clinical trials over 6-24 months.

Structural damage in rheumatoid arthritis as visualized through radiographs

Several agents show an effect on reducing radiographic progression in rheumatoid arthritis. It is tempting to retrospectively compare the effects of these agents on radiographic progression across clinical trials. However, there are several limitations in interpreting and comparing radiographic results across clinical trials. These limitations, including study designs, patient characteristics, durations of follow-up, scoring methodologies, reader reliability, radiograph sequence, handling of missing data, and data presentation, will be discussed. The consequences are illustrated with several examples of recent clinical trials that show an effect on radiographic progression. A guide in the interpretation and clinical relevance of radiographic results is presented, with the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy used as an example.

Radiographic progression in rheumatoid arthritis: Does it reflect outcome? Does it reflect treatment?

Although there is clear face validity that structural damage is related to outcome, it is difficult to prove this. Recently, more evidence became available that structural damage, as assessed on...

Recent advances in the treatment of the seronegative spondyloarthropathies.

The observation that anti-tumor necrosis factor (anti-TNF) therapies dramatically reduce joint pain and inflammation and retard radiographic progression in rheumatoid arthritis (RA) has created a considerable amount of enthusiasm among rheumatologists and has set new treatment standards for patients with inflammatory joint disease. A central question that has emerged is whether these agents are effective in treating the seronegative spondyloarthropathies (SpA). A related question is whether second-line agents such as methotrexate (MTX) can improve axial inflammation and functional measures if administered early in disease. The SpA are a cluster of inflammatory arthridites encompassing ankylosing spondylitis (AS), psoriatic arthritis (PsA), Reiter's syndrome/reactive arthritis (ReA), and the arthritis associated with inflammatory bowel disease. These disorders share similar clinical and immunogenetic features including axial arthritis and enthesopathy, a general predilection for males and patients positive for the MHC class I alleles, the absence of rheumatoid factor, and association with infections of the intestinal and genitourinary tracts. Reclassification of SpA based on axial or peripheral involvement may be more relevant from a pathophysiologic and therapeutic perspective than the current stratification, given the strong association between axial disease and the HLAB27 allele and the relative resistance of axial disease to conventional anti-inflammatory therapy.

A T cell receptor beta chain variable region polymorphism associated with radiographic progression in rheumatoid arthritis.

In rheumatoid arthritis (RA) genetic factors influence susceptibility to disease and progression. Identifying these genetic factors may give more insight into the aetiology and pathogenesis of this disease. Furthermore, if these genetic markers can predict progression in an early stage of disease, timely institution of more aggressive treatment in patients with a bad prognosis may help to prevent joint damage. Several studies have shown that HLA-DRB1 alleles are associated with RA, whereas others have indicated that genes not linked to the HLA complex are also involved. Candidates for such genes are the T cell receptor (TCR) alpha/beta genes. The association of a polymorphism in a TCR beta chain variable region gene (TCR-V beta 8) with both risk for RA and radiographic progression of joint disease was analysed after a three year follow up. A cohort of 118 white patients with a duration of disease shorter than one year at entry, and 110 white controls were typed for this (BamHI) TCR-V beta 8 polymorphism. The distribution of the two alleles, 2.0 and 23.0 kb, was identical in patients and controls. Radiographic progression (modified Sharp method) after a three year follow up, studied in 111 patients, was significantly less in the group possessing the 2.0 kb allele (p = 0.03). This does not confirm the reported association of the (BamHI) TCR-V beta 8 2.0 kb allele with RA. By contrast with previous findings in smaller studies, in the present study this 2.0 kb allele was protective against radiographic progression. Because well known prognostic variables in RA were corrected for, the findings indicate that the TCR-V beta 8 polymorphism studied is a new prognostic marker for this disease.

The effects of drug therapy on radiographic progression of rheumatoid arthritis. results of a 36‐week randomized trial comparing methotrexate and auranofin

To determine the effects of drug therapy (methotrexate [MTX] versus auranofin [AUR]) on radiographic progression in patients with active rheumatoid arthritis (RA). We conducted a 9-month randomized, multicenter, double-blind trial comparing MTX and AUR. Standardized radiographs of the hands and wrists were obtained at baseline and at completion of the study. Four experienced bone radiologists graded the radiographs for erosions, joint space narrowing, erosion healing, and reparative bone formation. Two hundred eighty-one patients were enrolled in the study. Radiographs were available on 167 of the 183 who completed the trial. After 9 months of therapy, there was a significantly greater worsening of the erosion score in the AUR group (mean +/- SEM change of 1.67 +/- 0.4) compared with the change in the MTX group (0.60 +/- 0.3) (P = 0.040). There was also a significantly greater worsening of the joint space narrowing score in the AUR group compared with the MTX group (1.36 +/- 0.3 versus 0.42 +/- 0.2) (P = 0.007). There was no difference demonstrated between groups in healing of erosions or in reparative bone formation. The rate of radiographic progression in patients with RA, as measured by erosion score and joint space narrowing score, was demonstrated to be lower in those treated with MTX, as compared with AUR, over a 36-week period.

Zur Erfassung der röntgenologischen Progredienz bei chronischer Polyarthritis

The radiographic progression of rheumatoid arthritis can be graded on a 0-IV scala. For this purpose five objektive criteria are used: a) destruction, b) osteoporosis, c) narrowing of joint space, d) luxation and e) ankylosis. The grading of the radiographic progression is defined by the extent and the number of the measured alterations. The radiographic progression can be registered yearly.

Radiographic progression of rheumatoid arthritis related to some clinical and laboratory parameters.

In 188 patients followed for 3 to 12 years, the radiologic course of rheumatoid arthritis was assessed in 20 joint groups. A severe course in most joints was related to the presence of rheumatoid factor and to high values of the ESR. Granulocyte-specific antinuclear antibodies were related to a severe course in most joints. The presence of nodules, the Rose-Waaler titre and the presence of organ non-specific antinuclear antibodies were generally unrelated to the course of the disease.