A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs. One-year outcomes of a randomized controlled trial of an educational-behavioural joint protection programme for people with rheumatoid arthritis. Auranofin improves outcome in early rheumatoid arthritis. Results from a 2-year, double blind placebo controlled study. Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study. Comparison of azathioprine, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial. Preliminary evaluation in rheumatoid arthritis activity in patients treated with TNF-alpha blocker plus methotrexate versus methotrexate or leflunomide alone. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab. Toxicity of methotrexate compared with azathioprine in the treatment of rheumatoid arthritis. A case-control study of 131 patients. Is a long-term high-intensity exercise program effective and safe in patients with rheumatoid arthritis? Results of a randomized controlled trial.
In rheumatoid arthritis (RA), intramuscular (IM) pulsed depomedrone expedites an immediate response to disease modifying antirheumatic drugs (DMARDs). Although IM depomedrone is also widely used to treat disease flares in patients treated with DMARDs, its effect on radiological progression has not been assessed.
                To evaluate the benefits of 120 mg IM depomedrone versus placebo in patients with established RA whose disease was inadequately controlled by existing DMARDs.
                In a 2 year prospective randomised controlled trial patients were assessed using the ILAR/WHO core dataset, disease activity score (DAS28), x ray examination of hands and feet scored by Larsen's method, and bone densitometry.
                291 patients with RA were screened, 166 were eligible, and 91 consented and were randomised. Disease activity improved more rapidly in the steroid treated patients than with placebo, but after 6 months no difference remained. A small but significant reduction in erosive damage in the steroid group compared with placebo was also found. More adverse reactions occurred in the steroid treated group than in the placebo patients (55 v 42), especially those reactions traditionally related to steroids (16 v 2), including vertebral fracture, diabetes, and myocardial infarction. Hip bone density fell significantly in steroid treated but not placebo patients.
                IM depomedrone improved disease activity in the short term and produced a small reduction in bone erosion at the cost of a significant increase in adverse events. Despite the initial benefit of IM depomedrone, when patients respond suboptimally to a DMARD they should not be given long term additional steroids but should be treated with alternative or additional DMARDs. Joint protection aims to reduce pain and local inflammation, preserve the integrity of joint structures and improve function. There is evidence that it can improve pain and function in the short term, but the long-term effects are uncertain. This study evaluated the effects of joint protection in early rheumatoid arthritis (RA).
                A randomized, controlled, assessor-blinded trial of duration 1 yr was conducted. Two interventions (both 8 h) were compared: standard arthritis education, including 2.5 h of joint protection education based on typical UK practice; and a joint protection arthritis education programme, using educational-behavioural teaching methods. Assessments were made at entry and 6 and 12 months.
                Sixty-five people with RA attended the joint protection programme and 62 the standard programme. The groups were matched for age (51 and 49 yr), disease duration (21 and 17.5 months) and use of non-steroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs. In comparison with the standard group, the joint protection group significantly improved with respect to adherence to the joint protection programme (P=0.001), hand pain (P=0.02), general pain (P=0.05), early morning stiffness (P=0.01), self-reported number of disease flare-ups (P=0.004), visits to the doctor for arthritis (P<0.01), and the AIMS2 (Arthritis Impact Measurement Scales) activities of daily living scale (P=0.04). A trend to improved swollen joint counts was identified (P=0.07). Within-group analyses also showed improvements in arthritis self-efficacy and perceived control. Hand deformity scores continued to increase in both groups.
                We found significant improvements in adherence, pain, disease status and functional ability amongst those attending the joint protection programme. Benefits became more apparent with time, suggesting that joint protection can help slow the progression of the effects of RA over and above the effects of drug therapy. The effect of early initiation of auranofin (AF) therapy on outcome measures was studied in a controlled 24-month double blind trial in 138 patients with early rheumatoid arthritis (RA) using an intent to treat approach. Patients were randomized to AF or placebo but in case of insufficient effect or intolerable adverse events, they switched to open disease modifying antirheumatic drug therapy. Patients who started AF fared significantly better in improved joint swelling. Stanford Health Assessment Questionnaire index, Keitel functional test, and mental depression, and furthermore, radiologic progression was significantly retarded. Our results support a disease modifying beneficial effect of AF in early active RA.se Optimal use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies. Aim: To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP.
                A randomised controlled study of step-up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) > or =2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS.
                At 6 months, 191 (28%) patients had a DAS <2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy.
                In this "true-to-life" study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies. To compare the relative safety and efficacy of azathioprine (AZA), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA).
                Two hundred twelve patients with active RA were entered into a 24-week prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups.
                One hundred fifty-eight patients finished 24 weeks of the study. There were no remissions seen but response rates were greater than 30% for all outcome measures. Combination therapy was not statistically superior to MTX therapy alone, but both combination therapy and MTX alone were superior to AZA alone when patients were analyzed by intent-to-treat and with withdrawals treated as therapy failures. If only patients who continued taking the therapy were analyzed, the mean improvement was greater for AZA therapy than for MTX, while the combination remained the most active. Adverse effects on the gastrointestinal tract and elevations of liver enzyme levels were the most frequent causes for discontinuations.
                Both combination therapy and MTX alone were superior to therapy with AZA alone for active RA but were not statistically different in their effect on outcome assessment. Methotrexate (MTX) is a first-line disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA). Leflunomide (LEF) and the biologic agents entered the arsenal of DMARDs in 1998. Therapeutic properties of new drugs are still under survey. The purpose of this study was to evaluate and compare the efficacy of MTX, LEF and a biologic agent (TNF-alpha blocker) combined with MTX in reducing disease activity in RA. Seventy-eight patients with active RA underwent a 24-week treatment with MTX 15 mg/week (30 pts), LEF 20 mg/day (30 pts) or a TNF-alpha blocker (etanercept 25 mg 2x weekly or infliximab 3 mg/kg in the week 0, 2, 6 and every 8 weeks thereafter) plus MTX 15 mg/week (18 pts). Only patients with RA resistant to MTX were included in groups receiving LEF or a biologic agent. During follow-up, patients' characteristics, disease characteristics, and clinical and laboratory data were registered. RA activity was evaluated using the ESR, tender and swollen joint counts, the duration of morning stiffness, disease activity score-28 (DAS 28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Treatment efficacy was demonstrated with ACR 20, 50 and 70 criteria. All groups revealed statistically significant improvement in all disease activity parameters measured. The percentage improvements were similar in groups treated with MTX and LEF and--except for VAS--significantly greater in the group treated with a biologic agent. Disease activity assessed by DAS 28 decreased significantly in all groups: the results were comparable in groups treated with MTX and LEF and significantly more prominent in the group treated with a TNF-alpha blocker. The ACR 20, 50 and 70 improvements amounted, respectively: 100, 50 and 7% in MTX group 87, 60 and 13% in LEF group and 100, 83 and 50% in a biologic agent group. The study revealed equal effectiveness of MTX and LEF in reducing disease activity in rheumatoid arthritis. The efficacy of a TNF-alpha blocker combined with MTX was higher than that of each conventional DMARDs, especially with regard to ACR 70 criteria (considerable improvement after treatment). LEF was equally effective as MTX in patients unable to continue MTX treatment due to the drug's ineffectiveness. To evaluate the ability of tocilizumab (a humanised anti-IL-6 receptor antibody) monotherapy to inhibit progression of structural joint damage in patients with RA.
                In a multi-centre, x ray reader-blinded, randomised, controlled trial, 306 patients with active RA of <5 years' duration were allocated to receive either tocilizumab monotherapy at 8 mg/kg intravenously every 4 weeks or conventional disease-modifying antirheumatic drugs (DMARDs) for 52 weeks. Radiographs of hands and forefeet were scored by the van der Heijde modified Sharp method.
                Patients had a mean disease duration of 2.3 years and a disease activity score in 28 joints of 6.5 at baseline. Mean total modified Sharp score (TSS) was 29.4, which was very high despite the relatively short disease duration. At week 52, the tocilizumab group showed statistically significantly less radiographic change in TSS (mean 2.3; 95% CI 1.5 to 3.2) than the DMARD group (mean 6.1; 95% CI 4.2 to 8.0; p<0.01). Tocilizumab monotherapy also improved signs and symptoms. The overall incidences of AEs were 89% and 82% (serious AEs: 18% and 13%; serious infections: 7.6% and 4.1%) in the tocilizumab and DMARD groups, respectively.
                Tocilizumab monotherapy was generally well tolerated and provided radiographic benefit in patients with RA. One hundred thirty-one patients with rheumatoid arthritis treated with either azathioprine sodium (n = 37, 102.7 +/- 32.9 mg/d) or methotrexate sodium (n = 94, 8.4 +/- 3.0 mg/wk) were followed up for 38 +/- 23.3 months to determine the nature, frequency, and potential predictors of "major" toxic reactions. Thirty-one methotrexate-treated patients (33%) and 11 patients (30%) receiving azathioprine experienced a major toxic reaction during the study period. With the case-control method, no predictors of major toxic reactions secondary to azathioprine therapy were found. Sex, drug dosage, response to prior slow-acting antirheumatic drug therapy, concurrent use of salicylates, and age did not predict major toxic reactions secondary to methotrexate treatment, but the methotrexate-treated patients who experienced a major toxic reaction had a significantly greater mean level of blood urea nitrogen at the time of their reaction compared with the control group. Life-table analysis suggested toxic reactions posed a greater risk of treatment termination in methotrexate-treated patients compared with the lack or loss of efficacy. This trend was not apparent in the azathioprine group. The majority of patients in each treatment group (79 for methotrexate and 29 for azathioprine) experienced one or more "minor" toxic reactions during the follow-up period. There are insufficient data on the effects of long-term intensive exercise in patients with rheumatoid arthritis (RA). We undertook this randomized, controlled, multicenter trial to compare the effectiveness and safety of a 2-year intensive exercise program (Rheumatoid Arthritis Patients In Training [RAPIT]) with those of physical therapy (termed usual care [UC]).
                Three hundred nine RA patients were assigned to either the RAPIT program or UC. The primary end points were functional ability (assessed by the McMaster Toronto Arthritis [MACTAR] Patient Preference Disability Questionnaire and the Health Assessment Questionnaire [HAQ]) and the effects on radiographic progression in large joints. Secondary end points concerned emotional status and disease activity.
                After 2 years, participants in the RAPIT program showed greater improvement in functional ability than participants in UC. The mean difference in change of the MACTAR Questionnaire score was 2.6 (95% confidence interval [95% CI] 0.1, 5.2) over the first year and 3.1 (95% CI 0.7, 5.5) over the second year. After 2 years, the mean difference in change of the HAQ score was -0.09 (95% CI -0.18, -0.01). The median radiographic damage of the large joints did not increase in either group. In both groups, participants with considerable baseline damage showed slightly more progression in damage, and this was more obvious in the RAPIT group. The RAPIT program proved to be effective in improving emotional status. No detrimental effects on disease activity were found.
                A long-term high-intensity exercise program is more effective than UC in improving functional ability of RA patients. Intensive exercise does not increase radiographic damage of the large joints, except possibly in patients with considerable baseline damage of the large joints.
Azathioprine appears to have a statistically significant benefit on the disease activity in joints of patients with RA. This evidence however is based on a small number of patients, included in older trials. Its effects on long-term functional status and radiological progression were not assessed due to lack of data. Toxicity is shown to be higher and more serious than that observed with other disease-modifying anti-rheumatic drugs (DMARDs). Given this high risk to benefit ratio, there is no evidence to recommend the use of azathioprine over other DMARDs.