A simple index to assess disease activity in rheumatoid arthritis

Changes in clinical and laboratory measures of disease activity were studied prospectively in 12 European centers. Altogether 282 rheumatoid patients were evaluated during 6 months of therapy with slow-acting drugs. Patients' global assessment was taken to indicate overall response. The number of swollen joints and number of tender joints correlated highly with this. The erythrocyte sedimentation rate (ESR) correlated less well but was more uniform across centers. Grip strength, C-reactive protein and hemoglobin performed poorly between centers. There were cultural and linguistic difficulties using the Health Assessment Questionnaire in a European setting. Physician's global assessments were similar to the patient's global assessments and provided redundant information. The best measures are: the number of swollen joints, the number of tender joints, the ESR, and the patient's global assessment. It may also help to measure articular pain.     

Radiographic outcome of recent-onset rheumatoid arthritis: a 19-year study of radiographic progression

OBJECTIVE: To describe the longitudinal radiographic course of rheumatoid arthritis (RA), and to identify and quantitate predictors of radiographic progression. METHODS: This prospective, longitudinal study of radiographic progression and clinical predictors of RA involved 256 patients with RA who were seen within the first 2 years of disease (mean 0.77 years) and were followed up for up to 19 years. Participants underwent a total of 6,278 clinical assessments (mean 24.5) and 934 paired radiographs (mean 3.1, range 2-6). Clinical assessments at every visit included determination of the erythrocyte sedimentation rate (ESR), grip strength, pain scores, tender joint counts, and anxiety and depression measurements. Regression analyses utilized time-integrated predictors. RESULTS: Overall, radiographic progression rates, as measured by the summary Sharp scores, appeared constant over the course of RA. The strongest correlate of progression was the time-integrated ESR (rho=0.53). This association grew stronger with time. At 0-5 years, 5-10 years, 10-15 years, and 15-20 years, correlations were 0.40, 0.50, 0.65, and 0.74, respectively, and for the period 10-20 years, the correlation was 0.67. In multivariate models, the mean ESR, mean grip strength, rheumatoid factor positivity, and tender joint count were independent predictors of radiographic progression. CONCLUSION: Radiographic damage occurs at a constant rate in RA, and is not greater early in RA or reduced later in the course of the illness. Acute-phase reactants are, by far, the strongest determinants of progression.     

A new approach to assessing rheumatoid arthritis (RA) disease activity using the American College of Rheumatology core set of disease activity measures for RA trials--a multi-center study

To characterize the American College of Rheumatology core set of disease activity measures for rheumatoid arthritis (RA) clinical trials (ACR core set measures) and the ACR definition of improvement of RA (ACR improvement definition), we studied 42 Japanese patients with active RA who were treated with DMARDs including mizoribine. Each patient's disease activity was assessed at the time of enrollment to the study and after 24 weeks using the ACR core set measures as well as the physical global assessment through the conventional measures. Twenty-five (60%) patients were discerned as showing improved by physicians through the conventional measures. This decision appeared to be based on improvement in Lansbury activity index (LAI) and C-reactive protein (CRP) value. Twelve of the 25 "improved" patients satisfied the ACR improvement definition. The 12 patients showed significant improvement in "outcome" measures including patients assessments of pain, disease activity, and physical function, compared to the 30 patients not satisfying the ACR definition. However, no significant differences were observed between these two groups in "process" measures including LAI, tender joint count, swallen joint count, or CRP value. In conclusion, the ACR core set measures including both process and outcome measures have potential to reflect clinical important changes on "real life" of patients with RA.     

Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist

OBJECTIVE: To evaluate the efficacy and safety of interleukin-1 receptor antagonist (IL-1Ra) in patients with rheumatoid arthritis (RA). METHODS: Patients with active and severe RA (disease duration <8 years) were recruited into a 24-week, double-blind, randomized, placebo-controlled, multicenter study. Doses of nonsteroidal antiinflammatory drugs and/or oral corticosteroids (< or =10 mg prednisolone daily) remained constant throughout the study. Any disease-modifying antirheumatic drugs that were being administered were discontinued at least 6 weeks prior to enrollment. Patients were randomized to 1 of 4 treatment groups: placebo or a single, self-administered subcutaneous injection of IL-1Ra at a daily dose of 30 mg, 75 mg, or 150 mg. RESULTS: A total of 472 patients were recruited. At enrollment, the mean age, sex ratio, disease duration, and percentage of patients with rheumatoid factor and erosions were similar in the 4 treatment groups. The clinical parameters of disease activity were similar in each treatment group and were consistent with active and severe RA. At 24 weeks, of the patients who received 150 mg/day IL-1Ra, 43% met the American College of Rheumatology criteria for response (the primary efficacy measure), 44% met the Paulus criteria, and statistically significant improvements were seen in the number of swollen joints, number of tender joints, investigator's assessment of disease activity, patient's assessment of disease activity, pain score on a visual analog scale, duration of morning stiffness, Health Assessment Questionnaire score, C-reactive protein level, and erythrocyte sedimentation rate. In addition, the rate of radiologic progression in the patients receiving IL-1Ra was significantly less than in the placebo group at 24 weeks, as evidenced by the Larsen score and the erosive joint count. IL-1Ra was well tolerated and no serious adverse events were observed. An injection-site reaction was the most frequently observed adverse event, and this resulted in a 5% rate of withdrawal from the study among those receiving IL-1Ra at 150 mg/day. CONCLUSION: This study confirmed both the efficacy and the safety of IL-1Ra in a large cohort of patients with active and severe RA. IL-1Ra is the first biologic agent to demonstrate a beneficial effect on the rate of joint erosion.     

Anticonvulsant effects of dipotassium clorazepate on hippocampal kindled seizures in rats

OBJECTIVE: To determine the reliability of some commonly used outcome measures in patients with rheumatoid arthritis. METHODS: We studied 22 consecutive patients with rheumatoid arthritis enrolled in a clinical trial in a tertiary care center. The study design consisted of a test-retest, in which the same rheumatologist evaluated all of the patients twice, with an interval between evaluations of 90 to 120 minutes. Statistical analysis of the data consisted of calculation of the weighted Kappa (kw) and the intraclass correlation coefficient (ICC). RESULTS: For the Ritchie articular index, kappa w = 0.83, ICC = 0.49, p < 0.0001; tender joint count, kappa w = 0.82, ICC = 0.49, p < 0.0001; physician's global assessment, kappa w = 0.79, ICC = 0.48, p < 0.0001; disease activity score, kappa w = 0.79, ICC = 0.49, p < 0.0001; utilities, kappa w = 0.71, ICC = 0.48, p < 0.0001; swollen joint count, kappa w = 0.7, ICC = 0.47, p < 0.0001; patient's global assessment, kappa w = 0.58, ICC = 0.44, p < 0.0001; pain kappa w = 0.45, ICC = 0.41, p < 0.0001. CONCLUSIONS: The reliability of most of the outcome measures was good. It was higher for those measurements evaluated by a rheumatologist and for the composite indexes. Those requiring patient participation need to be improved.     

Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis

BACKGROUND: The value of intensive combination therapy in early rheumatoid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day), methotrexate (7.5 mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day) with sulphasalazine alone. METHODS: 155 patients with early rheumatoid arthritis (median duration 4 months) were randomly assigned combined treatment (76) or sulphasalazine alone (79). Prednisolone and methotrexate were tapered and stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of five disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes without knowledge of treatment allocation. FINDINGS: At week 28, the mean pooled index was 1.4 (95% CI 1.2-1.6) in the combined treatment group and 0.8 (0.6-1.0) in the sulphasalazine group (p < 0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively, were improved according to American College of Rheumatology criteria. The clinical difference between the groups decreased and was no longer significant after prednisolone was stopped, and there were no further changes after methotrexate was stopped. At 28 weeks, the radiographic damage score had increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p < 0.0001). The increases at week 56 (2 [0-43] vs 6 [0-54], p = 0.004), and at week 80 (4 [0-80] vs 12 [0-72], p = 0.01) were also significant. Further analysis suggests that combined therapy immediately suppressed damage progression, whereas sulphasalazine did so less effectively and with a lag of 6 to 12 months. There were fewer withdrawals in the combined therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred later. INTERPRETATION: This combined-therapy regimen offers additional disease control over and above that of sulphasalazine alone that persists for up to a year after corticosteroids are stopped. Although confirmatory studies and long-term follow-up are needed, this approach may prove useful in the treatment of early rheumatoid arthritis.     

What do self-administered joint counts tell us about patients with rheumatoid arthritis?

OBJECTIVE: This report presents data from two sources showing that a self-administered joint count (SAJC) suitable for use in clinical settings provides information comparable with that of observer-assessed joint counts. METHODS: Patients were tested with a 1-page form containing a 40-joint mannequin on which they could mark their painful or swollen joints. The first sample of 110 patients was used to compare the SAJC with the tender or swollen joint counts (TJC or SJC) performed by a rheumatologist and to a battery of clinical and laboratory measurements. The second sample consisted of 240 rheumatoid arthritis (RA) patients enrolled in a cohort study of RA outcomes, in whom the relationship between the SAJC and health-related quality of life measures was examined. RESULTS: Test-retest reliability of the SAJC was excellent (ri = 0.89), as was its agreement with the observer-assessed TJC (ri = 0.78). The SAJC was significantly correlated (P < or = 0.01) to pain on a 10-point scale (r = 0.33), the McGill Pain Questionnaire (r = 0.27), the pain subscale of the Arthritis Impact Measurement Scales (AIMS) (r = 0.32), the duration of morning stiffness (r = 0.27), and to the AIMS subscales of physical function (r = 0.20), impact (r = 0.31), and global health (r = 0.29). The SAJC was inversely related to formal education (r = -0.32), but did not correlate significantly with the modified Health Assessment Questionnaire, walking velocity, grip strength, or erythrocyte sedimentation rate. The responsiveness of the SAJC was comparable with that of other measures commonly employed to assess RA outcomes. Either the SAJC or the TJC could be included alternatively in multivariate models to explain 7 of the 8 subscales of the Medical Outcomes Study Short Form-36 (SF-36) questionnaire. CONCLUSION: The SAJC is a reliable and responsive measure that agrees highly with the observer-assessed TJC and is significantly associated to the health-related quality of life of patients with RA. Given its low cost and ease of administration, it is suggested that SAJC be included in future studies of RA outcome in routine clinical practice.     

Risk factors for septic arthritis in patients with joint disease. A prospective study

OBJECTIVE: To quantify potential risk factors for septic arthritis, in order to identify a basis for prevention. METHODS: The occurrence of potential risk factors for septic arthritis in patients with joint diseases attending a rheumatic disease clinic was prospectively monitored at 3-month intervals over a period of 3 years. Potential risk factors investigated were type of joint disease, comorbidity, medication, joint prosthesis, infections, and invasive procedures. The frequencies of risk factors in patients with and those without septic arthritis were compared using multiple logistic regression analysis. RESULTS: There were 37 patients with and 4,870 without septic arthritis. Risk factors for developing septic arthritis were age > or = 80 years (odds ratio [OR] = 3.5, 95% confidence interval [95% CI] 1.4-8.6), diabetes mellitus (OR = 3.3, 95% CI 1.1-10.1), rheumatoid arthritis (OR = 4.0, 95% CI 1.9-8.3), hip and/or knee prosthesis (OR = 15, 95% CI 4.1-54.3), joint surgery (OR = 5.1, 95% CI 2.2-11.9), and skin infection (OR = 27.2, 95% CI 7.6-97.1). CONCLUSION: These findings indicate that preventive measures against septic arthritis in patients with joint diseases should mainly be directed at those with joint prostheses and/or skin infection.     

Sulphasalazine in psoriatic arthritis: a randomized, multicentre, placebo-controlled study

A prospective double-blind, placebo-controlled, randomized study of 24 weeks duration was carried out comparing the efficacy and tolerability of sulphasalazine (SSZ) versus placebo in patients with psoriatic arthritis. A total of 120 patients were included in nine centres. All patients had active disease and fulfilled the criteria of definite psoriatic arthritis of at least 3 months duration. They received either SSZ (2.0 g/day) or placebo. Efficacy variables included pain, patient's overall assessment of joint and skin improvement, morning stiffness, Ritchie articular index, ESR and CRP. An intention-to-treat (ITT) analysis was performed for the 117 patients who qualified (three patients did not qualify due to missing data after baseline). A per-protocol analysis was performed for the 81 patients who completed the 6 months study period (SSZ = 38, placebo = 43). Major reasons for withdrawal were inadequate response (SSZ = 4, placebo = 7) and adverse events (SSZ = 8, placebo = 12). Pain was the only statistically significantly different primary outcome variable at end point in favour of SSZ in the ITT analysis. No significant differences were present in other clinical or biological variables, although there was a trend in favour of SSZ for some variables. SSZ, at a dose of 2.0 g/day, appeared to be a safe treatment in patients with psoriatic arthritis. At this dosage, its efficacy was only demonstrated for the pain variable.     

The correlation of indium-111 joint scans with clinical synovitis in rheumatoid arthritis

OBJECTIVE: An inflammatory compartment radionuclide such as Indium-111 chloride (111InCl3) may offer advantages over bone seeking radionuclides in the assessment of active rheumatoid synovitis. As an iron analog, 111InCl3 binds iron complexing proteins including transferrin. Active rheumatoid synovitis is a transferrin receptor rich compartment, reflecting profound cellular activation and proliferation. We investigated 111InCl3 scanning for the detection of active rheumatoid arthritis (RA). METHODS: Nine patients satisfying ACR criteria for definite or probable RA were scanned twice at a 28-day interval. Patients were undergoing multiple medication changes with resultant fluctuating disease activity. Blinded readings were performed by an experienced nuclear medicine physician and correlated with simultaneous clinical examinations by a single rheumatologist. Sixteen assessed joint areas/patient and a total of 144 joint areas were available for analysis. RESULTS: Scintigraphy correlated with swollen and tender joint scores at both timepoints. Specificity was highest with stringent scoring. Sensitivity was lowest for small joints with lower 111InCl3 uptake relative to background. A receiver operator curve (ROC), generated to analyze the diagnostic value of varying 111InCl3 scan stringency, demonstrated utilization of the most accurate portion of the ROC curve by the reader. CONCLUSION: 111InCl3 joint scintigraphy correlates with clinically detectable rheumatoid synovitis, supporting the hypothesis that transferrin receptor levels reflect rheumatoid disease activity.     

The effect of soft cervical collars on persistent neck pain in patients with whiplash injury

Thirty-five male patients, aged 34-79 yr, with definite rheumatoid arthritis (RA) were recruited from out-patient clinics and randomized to receive monthly injections of testosterone enanthate 250 mg or placebo as an adjunct therapy for 9 months. Endpoints included disease activity parameters and bone mineral density (BMD). At baseline, there were negative correlations between the ESR and serum testosterone (r = -0.42, P < 0.01) and BMD (hip, r = -0.65, P < 0.01). A total of 29.6% of all patients had at least one vertebral fracture, most having multiple fractures. Back pain, however, was not more prevalent in fracture patients (55% vs 50%). Disease activity was significantly higher in the fracture group (joint score P < 0.05, rheumatoid factor P < 0.01). Thirty patients completed the trial, 15 receiving testosterone and 15 receiving placebo. There were significant rises in serum testosterone, dihydrotestosterone and oestradiol in the treatment group. There was no significant effect of treatment on disease activity overall, five patients receiving testosterone underwent a "flare'. Differences in mean BMD following testosterone or placebo were non-significant (spine: +1.2% vs -1.1%; femur: -0.3% vs +0.3%). There was no suggestion of a positive effect of testosterone on disease activity in men with RA.     

Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis

OBJECTIVE: To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody (cA2) (infliximab; Remicade, Centocor, Malvern, PA) given alone or in combination with low-dose methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHODS: In a 26-week, double-blind, placebo-controlled, multicenter trial, 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low-dose MTX were randomized to 1 of 7 groups of 14-15 patients each. The patients received either intravenous cA2 at 1, 3, or 10 mg/kg, with or without MTX 7.5 mg/week, or intravenous placebo plus MTX 7.5 mg/week at weeks 0, 2, 6, 10, and 14 and were followed up through week 26. RESULTS: Approximately 60% of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20% Paulus criteria for response to treatment, for a median duration of 10.4 to >18.1 weeks (P < 0.001 versus placebo). Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 (median duration 2.6 weeks; P=0.126 versus placebo). However, coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic, prolonging the duration of the 20% response in >60% of patients to a median of 16.5 weeks (P < 0.001 versus placebo; P=0.006 versus no MTX) and the 50% response to 12.2 weeks (P < 0.001 versus placebo; P=0.002 versus no MTX). Patients receiving placebo infusions plus suboptimal low-dose MTX continued to have active disease, with a Paulus response lasting a median of 0 weeks. A 70-90% reduction in the swollen joint count, tender joint count, and C-reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX. In general, treatment was well tolerated and stable blood levels of cA2 were achieved in all groups, except for the group receiving 1 mg/kg of cA2 alone, at which dosage antibodies to cA2 were observed in approximately 50% of the patients. CONCLUSION: Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in approximately 60% of patients with active RA despite therapy with low-dose MTX. When cA2 at 1 mg/kg was given with low-dose MTX, synergy was observed. The results of the trial provide a strategy for further evaluation of the efficacy and safety of longer-term treatment with cA2.     

Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Arthritis and Rheumatism Council Low Dose Glucocorticoid Study Group

OBJECTIVE: Prednisolone reduced the progression of joint destruction over 2 yr in early, active rheumatoid arthritis. The response to discontinuation of prednisolone under double-blind conditions is now reported. METHODS: A randomized, double-blind, placebo-controlled trial of prednisolone 7.5 mg daily in addition to routine medication over 2 yr in 128 patients with early rheumatoid arthritis, using radiological progression (changes in the Larsen score) and the development of erosions as primary outcome measures. Study medication was blindly discontinued and follow-up maintained for a further year. Other assessments included disability, joint inflammation, pain and the acute-phase response. RESULTS: Similar results were obtained when all available radiographs were included for each year of assessment (maximum 114) and when only patients with radiographs at all time points were included (75 patients). In these 75, the mean progression in the prednisolone group was 0.21 Larsen units in year 1, 0.04 units in year 2 and 1.01 units in year 3 (P = 0.587, 0.913 and 0.039 for change within each year, respectively). The equivalent placebo group means were 2.34, 1.00 and 1.63 Larsen units (P = 0.001, 0.111 and 0.012; difference between groups: 2.13, 0.96 and 0.67 units, P = 0.082, 0.02 and 0.622). The percentage of hands which had erosions at each time point was: prednisolone group: 27.8, 29.2, 34.7 and 39.2; placebo group: 28.2, 48.7, 59.0 and 66.5. There was little evidence for a flare in clinical symptoms after discontinuation of prednisolone. CONCLUSION: Joint destruction resumed after discontinuation of prednisolone. This corroborates the previously reported therapeutic effect and challenges current concepts of disease pathogenesis.     

Day and night pain measurement in rheumatoid arthritis

OBJECTIVE: An attempt was made to see if rheumatoid arthritis (RA) patients can use visual analogue scales (VAS) to distinguish and grade the severity of pain at night, during rest, and on joint movement and to determine if discriminate measurement of these three pain components enhances the value of VAS estimation. METHODS: Two hundred and fifty two consecutive RA patients were evaluated by a single observer using 10 cm VAS for pain at night, at rest during the day, and on movement. Values were correlated against age, disease duration, joint tenderness, swollen joint count, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and Larsen x ray scores. RESULTS: Night pain was recorded by 71 (28%) and this component of pain was lower than VAS scores for daytime rest and movement. However, those with nocturnal pain had significantly more joint tenderness (p < 0.0001), swollen joints (p < 0.0001), and higher ESR and CRP. Age, disease duration, and radiographic scores were similar in those with and without night pain. Correlations of joint tenderness were apparent for all three pain scores but only nocturnal pain correlated with swollen joints (p < 0.001) and CRP (p < 0.005). Age, disease duration, and radiographic severity correlated with daytime rest or movement scores but not nocturnal pain. CONCLUSION: Patients were able to distinguish and estimate the severity of pain at rest, on movement, and at night. The occurrence of night pain characterised those with more active disease and night pain VAS measurement correlated best with measures of joint inflammation whereas daytime pain scores, both at rest and on movement, seemed influenced by the degree of permanent joint damage. Thus, discrete measurement of rest, movement, and nocturnal pain may provide useful information about RA disease status.     

Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis

The purpose of this study was to validate the results of a meta-analysis showing the efficacy of fish oil in rheumatoid arthritis with the results of a re-analysis of the complete primary data set. A Medline search yielded seven published papers. Three additional trials were found by contacting authorities in the field. Inclusion criteria included (1) a double-blind, placebo-controlled study, (2) use of at least one of seven predetermined outcome measures, (3) results reported for both placebo and treatment groups at baseline and follow-up, (4) randomization, and (5) parallel or cross-over design. Papers were scored for quality. Demographic and outcomes variables were collected. For the re-analysis of the primary data, the same variables were abstracted for the 395 individual patients randomized. The meta-analysis demonstrated that dietary fish oil supplementation for 3 months significantly reduced tender joint count (rate difference [RD] [95% CI] = -2.9 [-3.8 to -2.1] [p = 0.001]) and morning stiffness (RD [95% CI] = -25.9 [-44.3 to -7.5] [p < 0.01]) as compared with heterogeneous dietary control oils. The re-analysis of the primary data confirmed a significant reduction in tender joint count (p = 0.001) and in morning stiffness (p < 0.02) in the parallel analysis that ignored interaction terms. The analyses that included an interaction term between site and treatment again confirmed a significant reduction in tender joint count. The results for morning stiffness were similar to the meta-analysis, but did not quite reach statistical significance (p = 0.052-0.083). The relative improvements in the other outcome variables did not reach statistical significance. Use of fish oil improved the number of tender joints and duration of morning stiffness at 3 months as analyzed by both meta- and mega-analysis. The fuller mega-analysis confirmed the results of the meta-analysis. The advantages of mega-analysis were as follows: (1) the ability to analyze the homogeneity of the patient populations, (2) the ability to make clinically sensible adjustments in the form of the comparison, and (3) the ability to examine subsets of the data.     

A long-term five-year randomized controlled trial of hydroxychloroquine, sodium aurothiomalate, auranofin and penicillamine in the treatment of patients with rheumatoid arthritis

OBJECTIVE: To compare the efficacy of hydroxychloroquine, penicillamine, sodium aurothiomalate and auranofin in the treatment of active rheumatoid arthritis over a period of 5 yr. METHOD: Five hundred and forty-one patients with definite or classical rheumatoid arthritis were entered into an open randomized controlled trial with a flexible dose regimen designed to reflect clinical practice. Decisions to stop treatment with any one of the disease-modifying anti-rheumatic drugs (DMARDs) were based on an agreed trial protocol which defined criteria for adverse reactions and therapeutic failure. The managing physicians' decisions were confirmed in a separate monitor clinic. RESULTS: The proportion of patients who remained on their first DMARD or who were in remission at 5 yr was 53% for penicillamine, 34% for sodium aurothiomalate, 31%, for auranofin and 30% for hydroxychloroquine (P < 0.001). In patients who stayed on their first DMARD, all groups showed a 30-50% improvement in C-reactive protein, erythrocyte sedimentation rate, Ritchie Index and joint stiffness, and a deterioration in their Larsen score. There was no evidence of physician bias to explain the larger proportion of patients remaining on penicillamine for 5 yr. CONCLUSION: Despite the increased popularity of sulphasalazine and inmmunosuppressives, the drugs in this study continue to be used worldwide. The natural history of rheumatoid arthritis requires long-term follow up to establish drug efficacy. Evidence is needed as to whether the newer regimens will prove to be more effective and safer in the longer term than the commonly prescribed DMARDs. The data from this trial will provide a reference for comparison with future studies.     

Lactoferrin and lysozyme in arthritic exudates

Lactoferrin (LF) has been assayed by radioimmunoassay in plasma and arthritic exudates and compared with lysozyme (LZ) levels and leukocyte counts. The mean LF concentration in 38 rheumatoid arthritis (RA) exudates was 9.1 mg/l (range 0.02-39.2). In 30 non-RA exudates LF was 3.3 mg/l (range 0.01-14.6). The corresponding LZ levels were 7.4 mg/l (range 2.5-18.5) in RA and 4.7 (range 1.0-12.5) in non-RA fluids. Exudate/plasma ratios were much higher for LF than for LZ and higher in RA than in non-RA exudates, whereas leukocyte counts did not differ. The LF/leukocyte count ratio was significantly higher in RA than in the non-RA group. The data suggest a more prominent release of neutrophilic granulocyte components in RA than in non-RA arthritis.     

Factors predicting outcome of rheumatoid arthritis: results of a followup study

OBJECTIVE: To determine prognostic factors in rheumatoid arthritis (RA). METHODS: One hundred thirty-two women with definite RA were followed yearly from an early phase of the disease (symptoms < 5 years) for a mean duration of 6 years. The prognostic value of the first available clinical and laboratory variables and assessments of functional ability was related to several outcome measures (physician's opinion of disease severity, disease activity, radiological abnormalities, functional ability and number of prescribed 2nd-line drugs) by single predictor analysis and by logistic regression. RESULTS: The variables most predictive for one or more of the outcome measures were number of swollen joints, Ritchie score, health assessment questionnaire score, radiographical abnormalities, positive IgM rheumatoid factor (RF), positive IgG-RF, HLA-DR4, and an elevated percentage serum agalactosyl IgG. The accuracy of predicting outcome was calculated from several combinations of these variables, and varied between 70 and 80%. The accuracy based on a combination of the commonly available variables (number of swollen joints, IgM-RF and the erosion score), closely approximated the maximal accuracy that could be achieved. CONCLUSION: The outcome of RA can be predicted by a combination of variables that are commonly available in the clinical setting.     

Progression of joint damage in early active severe rheumatoid arthritis during 18 months of treatment: comparison of low-dose cyclosporin and parenteral gold

OBJECTIVE: This study compared the progression of joint damage in patients with early active severe rheumatoid arthritis (RA) treated with cyclosporin or parenteral gold. METHODS: In this open, randomized, multicentre study with a blinded radiological endpoint, 375 patients who had suffered from active severe RA for <3 yr were randomized to be treated for 18 months with low-dose cyclosporin or parenteral gold. The groups were stratified with regard to corticosteroid use. Primary efficacy variables were numbers of erosions, erosion score and the Larsen-Dale joint damage score. RESULTS: Joint damage progressed at similar rates in both treatment arms. In both groups, patients receiving corticosteroids had less X-ray progression. Rheumatoid factor positivity, high swollen joint count, high erythrocyte sedimentation rate and pre-existing X-ray abnormalities predicted progression of joint damage. Although numbers of serious adverse events were similar, more gold patients (n = 65) than cyclosporin patients (n = 45) withdrew from study medication because of adverse events. CONCLUSION: Cyclosporin was comparable to parenteral gold in retarding progression of joint damage and was better tolerated in terms of adherence to therapy. The open label design should be kept in mind when assessing this difference.