Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
11600749 A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the e 2001 Oct OBJECTIVE: Whether food intake can modify the course of rheumatoid arthritis (RA) is an issue of continued scientific and public interest. However, data from controlled clinical trials are sparse. We thus decided to study the clinical effects of a vegan diet free of gluten in RA and to quantify the levels of antibodies to key food antigens not present in the vegan diet. METHODS: Sixty-six patients with active RA were randomized to either a vegan diet free of gluten (38 patients) or a well-balanced non-vegan diet (28 patients) for 1 yr. All patients were instructed and followed-up in the same manner. They were analysed at baseline and after 3, 6 and 12 months, according to the response criteria of the American College of Rheumatology (ACR). Furthermore, levels of antibodies against gliadin and beta-lactoglobulin were assessed and radiographs of the hands and feet were performed. RESULTS: Twenty-two patients in the vegan group and 25 patients in the non-vegan diet group completed 9 months or more on the diet regimens. Of these diet completers, 40.5% (nine patients) in the vegan group fulfilled the ACR20 improvement criteria compared with 4% (one patient) in the non-vegan group. Corresponding figures for the intention to treat populations were 34.3 and 3.8%, respectively. The immunoglobulin G (IgG) antibody levels against gliadin and beta-lactoglobulin decreased in the responder subgroup in the vegan diet-treated patients, but not in the other analysed groups. No retardation of radiological destruction was apparent in any of the groups. CONCLUSION: The data provide evidence that dietary modification may be of clinical benefit for certain RA patients, and that this benefit may be related to a reduction in immunoreactivity to food antigens eliminated by the change in diet.
9179174 Effects of exercise on fatigue, aerobic fitness, and disease activity measures in persons 1997 Jun The effects of 12 weeks of low-impact aerobic exercise on fatigue, aerobic fitness, and disease activity were examined in a quasi-experimental time series study of 25 adults with rheumatoid arthritis (RA). Measures were obtained preintervention, midtreatment (after 6 weeks of exercise), end of treatment (after 12 weeks of exercise), and at a 15-week follow-up. ANOVAS for repeated measures showed that those subjects who participated more frequently reported decreased fatigue, while those who participated less frequently reported an increase in fatigue. All subjects, on average, showed increased aerobic fitness and increased right and left hand grip strength, decreased pain, and decreased walk time. There were no significant increases in joint count or sedimentation rate. Significant improvements in measures at the 15-week follow-up also were found. Findings indicate that persons with RA who participate in appropriate exercises may lessen fatigue levels and experience other positive effects without worsening their arthritis.
10364918 Examination of synovial fluid and serum hyaluronidase activity as a joint marker in rheuma 1999 Mar OBJECTIVE: Hyaluronic acid (HA) is an important joint marker and the substrate for hyaluronidase (HAase). Synovial fluid (SF) and serum HAase were measured to investigate the potential use of HAase as a joint marker in rheumatoid arthritis (RA) and osteoarthritis (OA) patients. METHODS: The subjects were 39 patients with RA and 42 patients with OA. HAase activity was measured by zymography and its relation with various parameters examined statistically. RESULTS: In RA SF a positive correlation (r = 0.458, p = 0.0186) was found between SF HAase activity and the concentration of serum C reactive protein. A positive correlation (r = 0.45, p = 0.024) was also found between SF HAase activity and platelet count in the RA group. Serum HAase activity in the RA group was significantly higher than in the OA group (p < 0.0001) and normal controls (p < 0.0001). CONCLUSION: The results suggest that SF HAase activity could be used as a marker of synovial inflammation.
10901117 Occupational determinants for rheumatoid arthritis. 2000 Jun OBJECTIVES: The aim of the present study was to evaluate possible occupational determinants for rheumatoid arthritis according to lifetime occupational history. METHODS: The cases were identified retrospectively from 1980 to 1995 at the University Hospital in Linköping, Sweden. The study comprised 422 cases and 859 randomly selected referents. Exposure data were collected through a postal questionnaire. RESULTS: For men, occupations with increased, although nonsignificant, odds ratios (OR) were farmers or farm workers [OR 1.8, 95% confidence interval (95% CI) 1.0-3.5], textile workers (OR 2.0, 95% CI 0.3-16.2), asphalters (OR 14.0, 95% CI 1.2-799.0 without latency requirement), and employees at service stations (OR 2.2, 95% CI 0.5-9.5). Among the women, hairdressers and beauticians (OR 2.7, 95% CI 0.8-8.6) had an increased risk for rheumatoid arthritis, as well as those exposed to hairdressing chemicals (OR 3.0, 95% CI 1.0-9.4) and meat products (OR 2.0, 95% CI 1.0-4.0). CONCLUSIONS: Several of the findings in this study are in accordance with those of previous studies. The increased risks of rheumatoid arthritis for asphalters and employees at service stations are however new associations previously not described in the literature.
9437834 Nephelometric determination of rat fibrinogen as a marker of inflammatory response. 1997 Oct 6 Following tissue injury or infection, the concentrations of several plasma proteins are altered substantially. The characteristic pattern of this change is termed the acute phase response, and can be observed in many different inflammatory situations, including surgical trauma, injury, infections, tissue infarction and several immunologically mediated states such as temporalis arteritis, polymyalgia rheumatica and rheumatoid arthritis. It is often of great clinical value to monitor the acute phase response in humans but the assays used to measure the acute response in man (e.g., erythrocyte sedimentation rate and C-reactive protein) is less well suited for experimental studies in the rat. We have instead developed a nephelometric assay for determination of fibrinogen as a marker of the inflammatory response in rats. The assay was used to monitor the inflammatory response in type II collagen arthritis in rats. This model involves the induction of severe polyarthritis and is a widely used animal model for rheumatoid arthritis (RA). Fibrinogen concentrations increased from 3.1 g/l before immunization to 10.5 g/l 2 weeks after the immunization, after which they gradually declined towards normal levels. This pattern of fibrinogen alterations correlated well with the inflammatory phase of the arthritic response. Plasma fibrinogen may thus represent a rapid and sensitive marker of the acute phase response in the rat.
11157142 Human granzyme B mediates cartilage proteoglycan degradation and is expressed at the invas 2001 Jan OBJECTIVE: To investigate the cartilage-degrading capacity of granzyme B and the presence of granzyme B-positive cells at sites of erosion in the rheumatoid synovium. METHODS: Granzyme B was added to [(3)H]proline/[(35)S]sulphate-labelled cartilage matrices and to cartilage explants. Proteoglycan degradation was assessed by the release of (35)S and glycosaminoglycans into the medium and collagen degradation was assessed by the release of (3)H and hydroxyproline and by measuring the fraction of denatured collagen. Granzyme B expression was studied at the invasive front of the synovium by immunohistochemistry. RESULTS: Granzyme B induced loss of both newly synthesized, radiolabelled proteoglycans in cartilage matrices and resident proteoglycans of the cartilage explants. No effect on collagen degradation was found. Granzyme B-positive cells were present throughout the synovium and at the invasive front. CONCLUSION: The presence of granzyme B-positive cells at the invasive front of the synovium together with its ability to degrade articular proteoglycans supports the view that granzyme B may contribute to joint destruction in rheumatoid arthritis.
10815354 Willingness to pay for arthritis symptom alleviation. Comparison of closed-ended questions 2000 Winter OBJECTIVE: To compare two methods of measuring willingness to pay (WTP): closed-ended questions with and without follow-up. METHODS: A measurement experiment based on dichotomous choice contingent valuation survey data is reported. Marginal WTP estimates for alleviation of rheumatoid arthritis symptoms resulting from treatment with a novel anti-rheumatic agent, cA2 (TNF-alpha blockade), were calculated. Monte Carlo simulations were undertaken to evaluate the methods with respect to their statistical power. RESULTS: The estimated marginal WTP values using closed-ended questions with and without follow-up were DKK 637 (US $91) and DKK 1,268 (US $181), respectively. A Wilcoxon's signed-rank test showed that the difference of DKK 631 was significant. Moreover, including a follow-up question increases the precision of the result. Monte Carlo simulations showed that trade-offs between power (i.e., the probability of a correct rejection of a false null hypothesis), efficiency, and size may exist in the two models. CONCLUSIONS: There was a significant difference between the WTP estimates when using closed-ended questions with and without follow-up. When choosing between the models, however, power, efficiency, and size could be used as selection criteria.
9805851 A probable explanation for mild extra-articular manifestations in Indian patients of rheum 1998 Jul One hundred four Rheumatoid factor (RF) positive Rheumatoid Arthritis (RA) patients fulfilling ARA criteria were screened for extraarticular manifestations. Rheumatoid nodules were present in 2.8% cases. Other extraarticular manifestations such as pulmonary, cardiac, occular, renal or GI involvement were absent in these cases. However, circulating immune complexes (CICs) were highly significantly raised in all the RA patients (P < 0.001). From amongst these cases a limited number (8 cases) have been subjected to qualitative and quantitative analysis of CICs to look for whether there could be any relationship between these and mild extraarticular manifestations that were being noticed in our groups of patients. Finding showed IgG-IgG CICs in five, IgG-IgM in two and IgG-IgA in one case. Quantitative analysis revealed mean IgG 4.97 +/- 1.7 IU/ml, IgM 14.58 +/- 5.53 IU/ml and IgA 5.08 +/- 1.53 IU/ml on LD Solugen plates. Serum concentration of C3 was not reduced (94.1 +/- 8.9 mg/dl). Low IgM contents of CICs and no reduction in complement level is the likely explanation for less severe inflammatory manifestations seen in our study. The conclusion and findings have been discussed in the light of observation reported by the Western workers.
11031440 [The treatment experience of rheumatoid arthritis patients in an industrial region of the 2000 Jul The data submitted suggest that the most effective option in the treatment of rheumatoid arthritis is simultaneous employment of a nonsteroidal anti-inflammatory agent and metatrexate for 1.5 yr and courses of hormonotherapy, exercise therapy, and topical application to the joints of compresses with dimexide, heparin, and analginum as required and ultrasound with hydrocortisone as well. There was no increase in disability rates among patients with rheumatoid arthritis placed on the above combined treatment, which fact is also related to improvement of diagnosis rheumatoid arthritis, well-timed case follow-up, and prescription of courses of prophylactic treatment.
9410900 HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthri 1997 Nov 1 Certain HLA-DR alleles have been associated with predisposition to human rheumatoid arthritis (RA). There is also evidence that certain HLA-DQ alleles may also be important in determining susceptibility to RA. We have previously demonstrated that mice transgenic for HLA-DQ8, a DQ allele associated with susceptibility to RA, develop severe arthritis after type II collagen immunization. To investigate the influence of polymorphic difference at the DQ loci on susceptibility to arthritis, we generated mice transgenic for HLA-DQ6, an allele associated with a nonsusceptible haplotype. The DQ6 mice were found to be resistant to collagen-induced arthritis. We also assessed the combined effect of an RA-susceptible and an RA nonassociated DQ allele by producing double-transgenic mice expressing DQ6 and DQ8 molecules, representing the more prevalent condition found in humans where heterozygosity at the DQ allele is common. The double-transgenic mice developed moderate CIA when immunized with CII when compared with the severe arthritis observed in DQ8 transgenic mice, much like RA patients bearing both susceptible and nonsusceptible HLA haplotypes. These studies support a role for HLA-DQ polymorphism in human RA.
10201957 Importance of CD23 for collagen-induced arthritis: delayed onset and reduced severity in C 1999 Apr 1 Increased expression of the low affinity receptor for IgE, FcepsilonRII/CD23 has been observed in rheumatoid arthritis. In view of this, we have investigated the expression and influence of CD23 in collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis. CD23+ cells were analyzed in lymph nodes of DBA/1 mice immunized with bovine collagen type II (BCII) in CFA or with CFA only. The percentage of CD23+ lymph node cells was increased in both BCII/CFA- and CFA-immunized mice at 1, 3, and 7 wk after immunization compared with unimmunized mice, indicating a role for the adjuvant to trigger general inflammation and CD23 expression. To investigate the functional role of CD23 in CIA, CD23-deficient mice on the DBA/1 genetic background were studied. After immunization with BCII/CFA, these mice developed CIA with delayed onset and reduced severity compared with wild-type mice. These findings suggest that an increased number of CD23+ cells is part of an inflammatory response and that CD23 expression is of pathogenic importance in the arthritic process.
11327703 Significance of cathepsin B accumulation in synovial fluid of rheumatoid arthritis. 2001 May 4 We measured and compared the activities of various kinds of proteinases, such as cysteine, serine, aspartic, and metalloproteinases, in synovial fluids of 16 patients with rheumatoid arthritis (RA) and 18 patients with osteoarthritis (OA). More than 19-fold higher activity of cathepsin B and about 6-fold higher activity of prolylendopeptidase, compared to those of OA, were accumulated in RA fluid. Moreover, levels of cathepsins B and S using the corresponding sandwich enzyme immunoassays were statistically higher in RA fluid than those in OA. Significant amounts of 41-kDa and 35-kDa procathepsin L were detected in RA fluid using gelatin zymography, while 41-kDa enzyme alone was detected in OA. Cathepsin B in RA fluid could degrade collagen, and this degradation was suppressed by the addition of CA-074, a specific inhibitor of cathepsin B. Therefore, cathepsin B may participate in joint destruction of RA, and its inhibitor may be effective for RA care.
10674968 DQCAR 113 and DQCAR 115 in combination with HLA-DRB1 alleles are significant markers of su 1999 Dec We have investigated HLA region microsatellite polymorphisms in rheumatoid arthritis (RA) which are known to be associated with HLA class II alleles in the Korean population. Ninety patients with RA and 106 controls were employed for this study, in which TAP1CA, DQCAR, D6S273, HLA-DRB1, -DQA1 and -DQB1 allele typing were performed. DQCAR 113 (RR = 3.2, P<0.0002), DQCAR 115 (RR = 3.6, P<0.0001) and heterozygous DQCAR 113/115 (RR = 11.2, P<0.0001) frequencies were significantly increased in the RA group compared with the control group. The HLA-DRB1 genotypes of patients who had DQCAR 113/115 alleles were defined as DRB1*04 and/or DRB1*09. There was no significant difference between RA and controls in D6S273 and TAP1CA allele frequencies. We demonstrated that HLA-DRB1*0405 (RR = 6.6, P<10(-6)), DQA1*03 (RR = 5.2, P<10(-6)), DQB1*04 (RR = 3.5, P<0.002) alleles were useful markers of susceptibility to RA in Koreans. The frequency of HLA-DRB1*0405 was higher in DQCAR 113 allele-positive RA (68.1%) than in DQCAR 113 allele-negative (16.3%) and total RA (43.3%) groups, and the susceptibility risk of DQCAR 113 allele to RA was more increased in the DRB1*0405-positive group (RR = 5.5, P<0.04). On the other hand, DQCAR 115 allele was more significantly associated with susceptibility to RA in HLA-DRB1*0405-negative patients (RR = 5.1, P<0.0005), and the association between RA and HLA-DRB1*0405 was also significantly associated with DQCAR 115 allele-negative patients (RR = 13.2, P<0.00001) as compared with DQCAR 115 allele-negative control groups. HLA-DRB1*0405-DQA1*03-DQCAR113-DQB1*03 haplotype showed high relative risk value (RR= 17.7, P<0.0002). In conclusion, the DQCAR allele in combination with HLA class II, especially DR, is probably a useful risk marker for RA susceptibility in the Korean population.
11434475 Associations of isokinetic knee extensor and flexor strength with steroid use and walking 2001 Seventy-five women with rheumatoid arthritis according to the 1987 criteria of the American Rheumatism Association were examined. Mean age was 61.9 +/- 12.5 years, mean disease duration 14 years. Sixty-three were or had been on steroids (median cumulative prednisolone dose 2.5 g). Maximal voluntary knee extensor and flexor strength (Nm) was assessed at 30 degrees/s by an isokinetic dynamometer. Walking ability was expressed as walking and stair-climbing time (s). Markers of disease activity included number of swollen and tender joints, pain as recorded by the patients on a visual analogue scale (VAS), and disability as scored by the Stanford Health Assessment Questionnaire (HAQ). Muscle strength, walking time (50 m) and stair-climbing time were reduced on average by 30%, and increased by 28% and 54% (p<0.0001), respectively, compared to 67 age-, weight- and height-matched healthy women. Associations between muscle strength and cumulative or current steroid dose were not found after correction for age and disease duration. Significant linear correlations were found between knee extensor strength and walking time (r =-0.78, p<0.0001) and stair-climbing time (r = -0.76, p<0.0001). Similar correlations were found for flexor strength. The correlations remained significant (Rpartial ranging from -0.64 to -0.69, p<0.0001) in multiple regression analyses adjusting for age, height, weight, disease duration, number of swollen and tender joints, and VAS and HAQ scores. In conclusion, negative effects of steroids on muscle strength were not demonstrated. Leg muscle strength is an important and independent determinator of walking ability in RA.
10524687 The Prosorba column for treatment of refractory rheumatoid arthritis: a randomized, double 1999 Oct OBJECTIVE: To evaluate the efficacy and safety of the Prosorba column as a treatment for rheumatoid arthritis (RA) in patients with active and treatment-resistant (refractory) disease. METHODS: A sham-controlled, randomized, double-blind, multicenter trial of Prosorba versus sham apheresis was performed in patients with RA who had failed to respond to treatment with methotrexate or at least 2 other second-line drugs. Patients received 12 weekly treatments with Prosorba or sham apheresis, with efficacy evaluated 7-8 weeks after treatment ended. Patients were characterized as responders if they experienced improvement according to the American College of Rheumatology (ACR) response criteria at the efficacy time point. A data safety monitoring board (DSMB) evaluated interim analyses for the possibility of early completion of the trial. RESULTS: Patients in the trial had RA for an average of 15.5 years (range 1.7-50.6) and had failed an average of 4.2 second-line drug treatments prior to entry. After the completion of treatment of 91 randomized patients, the DSMB stopped the trial early due to successful outcomes. Of the 47 patients in the Prosorba arm, 31.9% experienced ACR-defined improvement versus 11.4% of the 44 patients in the sham-treated arm (P = 0.019 after adjustment for interim analysis). When results from 8 additional patients, who had completed blinded treatments at the time of DSMB action, were added to the analysis (n = 99), results were unchanged. The most common adverse events were a short-term flare in joint pain and swelling following treatment, a side effect that occurred in most subjects at least once in both treatment arms. Other side effects, although common, occurred equally as frequently in both treatment groups. CONCLUSION: Apheresis with the Prosorba column is an efficacious treatment for RA in patients with active disease who have failed other treatments.
10971781 Leflunomide and rheumatoid arthritis: a systematic review of effectiveness, safety and cos 2000 Aug OBJECTIVE: To assess the effectiveness, safety and cost implications of leflunomide treatment for rheumatoid arthritis. DESIGN: Systematic review. SETTING: Four trials retrieved from Medline, Embase, the Cochrane Library, Econlit, HMIC (Dhdata), HMIC (Helmis), HMIC (King's Fund Database) and Best Evidence3. MAIN OUTCOME MEASURES: Efficacy measures (including tender joint counts, swollen joint counts, assessment of functioning, Health Assessment Questionnaire, Modified Health Assessment Questionnaire, pain (visual analogue scale), Erythrocyte Sedimentation Rate, C-reactive Protein), radiological progression and treatment adverse events. RESULTS: Leflunomide therapy was demonstrated to be significantly superior to placebo in relation to the efficacy outcome measures and it slowed the radiological progression of patients' disease in three studies. Treatment success and duration of sustained response were also significantly superior than on placebo, as were quality of life measures. Leflunomide treatment was comparable to sulphasalazine and methotrexate with respect to efficacy, radiological progression and quality of life measures. The most common adverse effects leading to withdrawal from leflunomide treatment were gastrointestinal symptoms (diarrhoea and nausea), allergic reactions (rash and pruritus), alopecia, dyspepsia, hypertension and elevated transaminase levels. Weight loss and dizziness have also been reported for leflunomide therapy. Leflunomide is more expensive than most DMARDs, costing about pound400 a year more than sulphasalazine. CONCLUSION: Despite the small number of published articles relating to leflunomide treatment, the evidence suggests that leflunomide is similar in efficacy to both sulphasalazine and methotrexate, although with a differential pattern of side-effects. There is a need for further research to assess the long-term outcomes of leflunomide treatment.
10788542 A clinical study of CPH 82 vs methotrexate in early rheumatoid arthritis. 2000 Mar OBJECTIVES: The objectives of this study were to evaluate the therapeutic efficacy of CPH 82 in comparison with methotrexate (MTX) in adult patients with early, active rheumatoid arthritis (RA) and to compare the tolerance and safety profiles of the two drugs. METHODS: The study was a 24-week, double-blind, randomized study in 10 centres of 100 patients with active RA, with a disease duration of less than 2 yr at the start of treatment, which consisted of either CPH 82 300 mg/day or MTX 10 mg/week. The six primary effect variables were: number of swollen joints, Ritchie's articular index, patient's pain score, patient's global score, Health Assessment Questionnaire (HAQ) and C-reactive protein (CRP). Erythrocyte sedimentation rate (ESR), physician's global score and the efficacy according to the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) response criteria were also analysed. RESULTS: There was a significant improvement for both drugs in all variables. Significant differences between the drugs in favour of MTX were found only in patient's pain score, CRP and ESR. By the EULAR criteria, 76% and 86% were judged to be responders in the CPH 82 and MTX groups, respectively. By the ACR criteria, the corresponding figures were 58% and 64%. The most common side-effects were gastrointestinal, which were similar in both groups. The numbers of treatment failures due to adverse events were two with CPH 82 and 14 with MTX. CONCLUSIONS: The clinical effect of CPH 82 in this study was comparable to that of MTX at a dose of 10 mg/week. Both drugs reduced acute-phase reactants, MTX more effectively than CPH 82. The safety profile of CPH 82 was more favourable than that of MTX without folic acid supplementation.
10788538 Effects of creatine supplementation on muscle weakness in patients with rheumatoid arthrit 2000 Mar BACKGROUND AND OBJECTIVES: Patients with rheumatoid arthritis (RA) frequently suffer from muscle weakness. Oral administration of creatine has been shown to improve muscle strength in healthy subjects. The objective of this study was to examine the effect of oral creatine supplementation on muscle weakness, disease activity and activities of daily living in patients with RA. METHODS: During a period of 3 weeks, 12 patients with RA were treated with creatine monohydrate (20 g/day for 5 days followed by 2 g/day for 16 days). They were examined on entry and at the end of the study. The patients were investigated clinically, blood and urine samples were obtained, muscle biopsies were performed before and after treatment, muscle strength was determined, and self-administered patient questionnaires were completed. RESULTS: From all patients we were able to obtain full clinical and questionnaire data, while biopsies were taken from 12 patients at the start and from nine patients at the end of the study. Muscle strength, as determined by the muscle strength index, increased in eight of 12 patients. In contrast, physical functional ability and disease activity did not change significantly. The creatine concentration in serum and skeletal muscle increased significantly, while creatine phosphate and total creatine did not increase in skeletal muscle. The skeletal muscle creatine content was associated with muscle strength at baseline but not after administration of creatine. The changes in muscle strength were not associated with the changes in skeletal muscle creatine or creatine phosphate. CONCLUSION: Although the skeletal muscle creatine content and muscle strength increased with creatine administration in some patients with RA, a clear clinical benefit could not be demonstrated for this treatment when the patients were considered as one group.
11055006 [Pericardial effusion revealing cardiac amyloidosis in the course of rheumatoid arthritis] 2000 Sep Pericardial effusion is common in patients with rheumatoid arthritis. It is essentially a sign of pericardial involvement of the rheumatoid disease, but viral, bacterial and especially tuberculous pericarditis must not be excluded. Pericardial amyloidosis of the AA type is much less common and difficult to diagnose before cardiac biopsy even in cases of myocardial amyloidosis, as in the reported case, in which the classical association of microvoltage on the ECG and myocardial hypertrophy on echocardiography was absent. The absence of myocardial uptake of technetium-labelled pyrophosphates at myocardial scintigraphy and the absence of a restrictive profile on cardiac gamma-angiography were not suggestive of the diagnosis of amyloidosis. Pericardial and endomyocardial biopsy, justified by the negativity of the preceding investigations, provided an accurate histological diagnosis, a prognostic evaluation and was also useful for guiding management.
9266130 Why randomized controlled clinical trials do not depict accurately long-term outcomes in r 1997 May The randomized controlled clinical trial is the "gold standard" to evaluate therapeutic interventions, but is more effectively applied to studies of the short-term treatment of acute diseases than to the long-term treatment of chronic diseases. Clinical observations often provide more accurate outcome data in rheumatoid arthritis (RA) than clinical trials. Limitations of clinical trials to depict long-term outcomes in RA include a relatively short observation period, patient selection resulting from exclusion criteria, inflexible dosage schedules and concomitant drug therapies, evidence that some markers of inflammatory activity are suboptimal surrogate indicators of long-term articular damage, the fact that statistically significant results are not necessarily clinically important, the influence of the design on the results-despite a control group, ignoring of individual variation in reporting results, the non-standardized interpretation of side effects which introduces bias, distortion of the "placebo effect", and lack of capacity to detect rare side effects. The clinical trial represents only an initial step in the evaluation of a therapy for a chronic disease. Awareness of these limitations should lead to the improved design of clinical trials and clinical studies to improve the long-term outcome for people with RA.