A 12-month randomized controlled trial of patient education on radiographic changes and quality of life in early rheumatoid arthritis.
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OBJECTIVE: In rheumatoid arthritis, education programmes successfully impart knowledge but, notwithstanding issues of empowerment, this knowledge has to be translated into behavioural change to have a chance of improving disease outcome. Arguably, behavioural change must also occur early if outcomes are to be improved. For these reasons, we planned a study of patient education in early disease, with radiological damage and quality of life as the main outcome variables. METHODS: We performed a randomized controlled trial in people with rheumatoid arthritis of < 5 yr duration. The main intervention was a 4 week education programme, each weekly session lasting 2 h. Assessments were made at entry, at 4 weeks and at 12 months. The main outcome variables were the modified Larsen radiological score for the hands and the SF-36 quality of life questionnaire. Secondary outcome variables were the Health Assessment Questionnaire (HAQ), Ritchie Articular Index (RAI), Patient Knowledge Questionnaire (PKQ), Compliance Questionnaire (CQ), plasma viscosity (PV), pharmaceutical changes and consulting behaviour. RESULTS: The patient numbers were 34 (10 male, 24 female) for the control group and 43 (16 male, 27 female) for the education group. The groups were matched for age (56.5 yr for control, 55 yr for education), disease duration (3.5 yr vs 3.0 yr) and duration of second-line drug therapy (14 months vs 12 months). We found no significant difference between the groups for Larsen scores at 12 months, although scores for the education group were lower (39.5 vs 43.0, P = 0.13). The 'social functioning' and 'general health perception' subscales of the SF-36 showed a significant improvement in the education group, but no significant differences between groups were seen. No significant differences were found for the HAQ, RAI, PV and CQ, but the education group had more disease-specific knowledge than the control group at 12 months (PKQ scores: 17 vs 21, P = 0.0002). No differences were found for out-patient visits and in-patient admissions, but the education group had slightly more changes in second-line drugs during the study (0.43 changes/person in the control group, 0.51 changes/person in the education group). CONCLUSIONS: We found no significant difference between the groups in our primary outcome measures, but a trend in favour of the education group was found in radiological progression. Further studies of this kind, using larger patient numbers, are required since the difference may result from improved self-care, better compliance with joint protection strategies and, possibly, improved drug compliance. (+info)
Nuclear factor kappaB (NF-kappaB) pathway as a therapeutic target in rheumatoid arthritis.
(26/3077)
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint swelling and progressive destruction of cartilage and bone. Current RA treatments are largely empirical in origin and their precise mechanism of action is uncertain. Increasing evidence shows that chronic inflammatory diseases such as RA are caused by prolonged production of proinflammatory cytokines including tumor necrosis factor (TNF) and interleukin 1 (IL-1). The nuclear factor kappaB (NF-kappaB) plays an essential role in transcriptional activation of TNF and IL-1. NF-kappaB is induced by many stimuli including TNF and IL-1, forming a positive regulatory cycle that may amplify and maintain RA disease process. NF-kappaB and enzymes involved in its activation can be a target for anti-inflammatory treatment. Aspirin and sodium salicylate inhibit activation of NF-KB by blocking IkappaB kinase, a key enzyme in NF-kappaB activation. Glucocorticoids suppress expression of inflammatory genes by binding glucocorticoid receptor with NF-kappaB, and increasing expression of inhibitory protein of NF-kappaB, IkappaBalpha. Sulfasalazine and gold compounds also inhibit NF-kappaB activation. Continuing advances in our understanding of action mechanism of antirheumatic agents will benefit the future development of RA regimens with greater efficacy and less toxicity. (+info)
Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis.
(27/3077)
Treatment with a chimeric mAb to TNF-alpha has been shown to suppress inflammation and improve patient well-being in rheumatoid arthritis (RA), but the mechanisms of action of such treatment have not been fully explored. Here we show that in vivo administration of anti-TNF-alpha Ab, using a longitudinal analysis, results in the rapid down-regulation of a spectrum of cytokines, cytokine inhibitors, and acute-phase proteins. Marked diurnal variation in the serum levels of some of these were detected. These results were consistent with the concept of a cytokine-dependent cytokine cascade, and the degree of clinical benefit noted after anti-TNF-alpha therapy is probably due to the reduction in many proinflammatory mediators apart from TNF-alpha, such as IL-6, which reached normal levels within 24 h. Serum levels of cytokine inhibitors such as soluble p75 and p55 TNFR were reduced as was IL-1 receptor antagonist. Reductions in acute-phase proteins occurred after serum IL-6 fell and included serum amyloid A, haptoglobin, and fibrinogen. The latter reduction could be of importance, as it is a risk factor for atherosclerosis, which is augmented in RA patients. (+info)
Early referral, diagnosis, and treatment of rheumatoid arthritis: evidence for changing medical practice.
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OBJECTIVES: To study the delay in starting disease modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA), and any changes in medical practice between 1980 and 1997. METHODS: 198 consecutive RA patients attending the rheumatology clinics at a teaching hospital, for routine review, had their case sheet reviewed. The dates of symptom onset, general practitioner (GP) referral, first clinic appointment and first use of DMARD were recorded. Data were collected on the erythrocyte sedimentation rate, C reactive protein, rheumatoid factor, and the presence/absence of erosions at the first clinic assessment. Patients were split into four groups according to the date of their first clinic assessment-before 1986, 1987-9, 1990-3, and 1994-7. RESULTS: There was a sharp drop in the delay between symptom onset and GP referral (before 1986, 21 months; 1987-89, 23 months; 1990-3, 7 months; 1994-7, 4 months, p<0.03), and in the delay between first assessment at the rheumatology clinic and the start of DMARD treatment (before 1986, 32 months; 1987-89, 21 months; 1990-1993, 8 months; 1994-7, 1 month, p<0.001). The number of patients given DMARD treatment within six months of symptom onset increased from 5% (before 1994) to 44% (1994-7). Seventy three per cent of patients waiting more than a year from symptom onset to first clinic appointment already had erosive change, compared with 34% of patients seen within a year. CONCLUSIONS: Patients are being referred earlier in their disease, and DMARDs are prescribed sooner in the disease course. There has been a substantial increase in the proportion of patients treated with a DMARD within six months of symptom onset. (+info)
Association of HLA alleles and clinical features in patients with synovitis of recent onset.
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OBJECTIVE: To determine how HLA alleles are associated with the clinical disease patterns of patients with synovitis of recent onset. METHODS: The HLA alleles A, B, C, DRbeta1, and DQbeta1 were determined in a cohort of 211 patients (mean age 42 years, 64% female, 79% white) with recent-onset synovitis in 1 or more peripheral joints. At a mean disease duration of 33 weeks, 98 patients (46%) met the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), 38 (18%) met the European Spondylarthropathy Study Group criteria for spondylarthropathy (SpA), and 75 (36%) were classified as having undifferentiated arthropathy (UA). Controls were racially matched healthy individuals (n = 244). RESULTS: Shared epitope (SE) alleles were significantly more common in rheumatoid factor-positive (RF+) patients fulfilling the ACR RA criteria than in other patients with early arthritis (65% versus 35%; P < 0.001). In addition, the RA patients had by far the highest frequency of radiographic erosions (52% and 39% in RF+ and RF- RA, respectively, versus 3% and 9% in SpA and UA patients, respectively; P < 0.0001). The presence of SE alleles was a particularly strong predictor of early erosions in the RF- RA patients (odds ratio [OR] 6.8, 95% confidence interval [95% CI] 1.2-45). The presence of 2 SE alleles or an associated DQbeta1*0301 (DQ7) or DQbeta1*0302 (DQ8) allele appeared to modestly increase the risk of early erosions, although these DQ alleles were in strong linkage disequilibrium with DRbeta1*0401, both in the patient and in the control populations. B27 was linked with the presence of SE alleles in the patients, including those patients fulfilling the RA criteria, but not in the controls (12% versus 3%; P < 0.001). Enthesitis was present in 23 (11%) of 211 patients, was highly associated with B27 (OR 4.2, 95% CI 1.5-11.5), and surprisingly, was not a feature specific only to the SpA group. The B8-DR3 haplotype was significantly increased in the patient subgroups compared with controls (17% versus 7%; P < 0.01), although the clinical significance of this association is unclear. CONCLUSION: This study of HLA associations in a diverse cohort of early synovitis patients emphasizes the complex degree of genetic interaction between alleles at several major histocompatibility complex loci, which regulates clinical phenotypes. In particular, SE and B27, while predisposing patients to characteristic clinical syndromes, had an unexpected degree of association in this cohort, perhaps explaining the overlap in clinical features in many patients. (+info)
Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease activity.
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OBJECTIVE: YKL-40, also called human cartilage glycoprotein-39, is secreted by chondrocytes, synovial cells, macrophages and neutrophils. Studies have shown that YKL-40 is an autoantigen in rheumatoid arthritis (RA). We evaluated whether serum YKL-40 was related to disease activity in patients with RA. METHODS: Serum YKL-40 was determined by radioimmunoassay in 156 patients with RA during a 1 yr longitudinal study. RESULTS: Serum YKL-40 was increased in 54% of the patients with clinically active disease. Patients with clinically active disease initially who became inactive after 12 months had a significant decrease in serum YKL-40 (-30%, P < 0.002) and patients who changed from inactive to active disease had an increase in serum YKL-40. Patients who remained active had unchanged serum YKL-40 during the study. Serum YKL-40 decreased rapidly (-24% after 7 days, P < 0.01) during prednisolone therapy, and more slowly in patients treated with methotrexate only (-15% after 60 days, P < 0.01). Patients with early RA (disease duration < 3 yr, n = 50) and a persistently elevated serum YKL-40 were at risk of radiological disease progression as determined by Larsen score. CONCLUSION: Serum YKL-40 varies according to disease activity in RA, but provides in some respect information different from conventional markers. Our previous studies are consistent with a local release of YKL-40 in the arthritic joint followed by a secondary increase in serum YKL-40. YKL-40 may prove to be a new tool for the study of disease activity and pathophysiology of RA. (+info)
Utility of disease modifying antirheumatic drugs in "sawtooth" strategy. A prospective study of early rheumatoid arthritis patients up to 15 years.
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OBJECTIVES: To study long term utility of early, continual, and serial use of disease modifying antirheumatic drugs (DMARDs) in early rheumatoid arthritis (RA) in clinical setting. METHODS: A total of 135 patients with early RA were treated according to the "sawtooth" strategy and prospectively followed up to 15 years. DMARD survivals as well as reasons for drug terminations were documented and are reported here. RESULTS: During 1401 person years of follow up, a DMARD or a combination of two or several DMARDs (COMBOs) was started 606 times. A total of 528 drug periods were terminated because of inefficacy, adverse effects, remission, and other reasons in respective 270 (51.1%), 149 (28.2%), 32 (6.1%), and 77 (14.6%) cases. Severe drug related adverse events were rare. The median duration of DMARD periods of individual DMARDs or COMBOs was 10 months ranging from six to 18 months. Not a single DMARD/COMBO stood out favourably from the others with respect to ineffecacy, toxicity or drug survival. CONCLUSION: The use of serial DMARDs/COMBOs was safe even in the long run. Inefficacy rather than toxicity was the leading reason for drug terminations. More powerful drug therapies are needed. (+info)
Long-term toxicity of immune suppression in juvenile rheumatic diseases.
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Although there are not many studies which have addressed long-term outcomes in children with rheumatic disease treated with immunosuppressive agents, the data that are available, as well as information from adult studies, suggest significant long-term concerns with all the agents that have demonstrable efficacy. This must lead us to investigate new methods of treatment which will not only be more effective, but also less toxic. (+info)