Measuring health status in psoriatic arthritis: the Health Assessment Questionnaire and its modification

OBJECTIVE: The Health Assessment Questionnaire (HAQ) has proven to be a reliable and valid measure of outcome for a variety of arthritides. A recent modification of HAQ for spondyloarthropathy (HAQ-S) has also been reported. Our purpose was to evaluate the HAQ and HAQ-S as outcome measures in the assessment of patients with psoriatic arthritis (PsA). METHODS: The HAQ, including HAQ-S was administered to all patients attending our Psoriatic Arthritis Clinic between June and December, 1993. Clinical and radiological assessments were performed according to a standard protocol that measures disease activity, fibrositic tender points (TP), disease severity and damage. Analysis was performed using SAS for the PC. RESULTS: The patient population included 114 patients, 70 men and 44 women with a mean age of 49.3 years and a mean arthritis duration of 15.1 years. The mean HAQ score was 0.50, while the mean HAQ-S score was 0.53 (scores range 0 to 3 for this instrument). The overall HAQ and HAQ-S disability scores were highly correlated with several clinical measures of function, including grip strength (r = -0.63 and -0.59, respectively). American College of Rheumatology functional class (r = 0.59 and 0.60, respectively), as well as the number of fibrositic TP (r = 0.54 and 0.57, respectively). These disability scores also correlated highly with the overall number of actively inflamed joints (r = 0.49 and 0.50, respectively); however, they correlated only moderately or poorly with other measures of disease activity such as morning stiffness, total number of joint effusions, erythrocyte sedimentation rate (ESR) and the PASI score for psoriasis and with all measures of disease severity. A similar pattern of correlations was found between the individual subscales of the HAQ and HAQ-S and the clinical measures of function, activity, and severity, as well as between the pain scale and the various clinical measures. However, the correlations are generally lower. CONCLUSION: Our data suggest that HAQ and HAQ-S capture clinical measures of function and pain in PsA but do not correlate with disease severity. The HAQ and its modification for spondyloarthropathy may reflect fibromyaglia as a measure of pain and tenderness in these patients. Thus, the clinical assessment of disease activity and both clinical and radiological assessments of joint damage remain important outcome measures in PsA.     

Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group

BACKGROUND: Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis. METHODS: 358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat. FINDINGS: The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group. INTERPRETATION: Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.     

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.     

Long-term treatment of destructive rheumatoid arthritis with methotrexate

OBJECTIVE: To evaluate the tolerability and efficacy of methotrexate (MTX) treatment in patients with longstanding, progressive, active rheumatoid arthritis (RA) who had failed one or more disease modifying antirheumatic drugs (DMARD). METHODS: Two hundred seventy-one consecutive patients with RA in whom MTX treatment was introduced were followed at regular intervals for up to 108 months. Evaluations included the number of swollen joints, grip strength, patient assessment of pain and mobility, erythrocyte sedimentation rate (ESR), and hemoglobin. Radiographs of hands and feet were taken once a year and 32 joints were evaluated according to a modified Larsen score. RESULTS: Of the 271 patients, 269 had prior treatment with one DMARD, primarily parenteral gold, and 58% with 2 or more DMARD. MTX was started parenterally in all patients in doses between 15 and 25 mg weekly and continued by oral medication in most of the cases. Eighty-three percent of patients complained of adverse events. The most common side effects were nausea, hair loss, transaminase increase, and stomatitis. In 45 patients (16.5%), MTX was withdrawn because of side effects, mostly during the first year. Sixteen patients (5.9%) died during followup, mainly due to myocardial infarction, heart failure, stroke, or cancer. After one year, 78.7% and after 5 years 60.3% of the patients were still taking MTX. Number of swollen joints, ESR, grip strength, patient assessment of pain, and mobility improved significantly at all measurement points. Improvement in the swollen joint count and the ESR of over 50% was seen in more than 50% of patients. Inactivation of the disease, defined as < 2 swollen joints, ESR < 20 mm, and no concomitant steroid use, occurred in 8-14% of patients. Steroid intake was significantly reduced. In spite of clinical improvement the modified Larsen score showed a progression in the vast majority of patients. CONCLUSION: Even in patients with longstanding, active, destructive RA who failed one or more DMARD, MTX treatment is well tolerated and improves clinical and biochemical disease activity significantly, while radiographic progression is still present.     

tRNA-guanine transglycosylase from Escherichia coli: recognition of full-length ''queuine-cognate'' tRNAs

OBJECTIVE: To determine clinical variables useful in predicting the prognosis of patients with early rheumatoid arthritis (RA) by investigating the relationship between clinical variables and radiological progression. METHODS: One hundred eighteen patients with early RA whose symptoms developed within the previous year were enrolled in a prospective study. Data from the 98 patients who completed the 2 year study were analyzed, using the number of erosive joints and Larsen's score as the outcome of RA. RESULTS: Increases in the number of erosive joints at 12 months after entry into the study were significantly correlated with the number of swollen joints (r = 0.510), erythrocyte sedimentation rate (ESR) (r = 0.404), and C-reactive protein (CRP) (r = 0.487) at 6 months. The same results were seen using Larsen's score as the measure of outcome. The average number of erosive joints or mean Larsen's score at 12 months was higher in patients whose levels of CRP were high at 6 months and suppressed by 12 months, but increased much less in patients whose levels of CRP were successfully suppressed by 6 months. More joint erosions were noted in patients with positive rheumatoid factor (RF) than in RF negative patients. CONCLUSION: Joint erosions appeared with a certain time lag after active synovitis. Earlier introduction of effective treatment is recommended for the prevention of RA joint damage. The presence of RF, number of swollen joints, ESR, and levels of CRP at 6 months after starting therapy are the most useful variables to predict radiological progression in patients with early RA.     

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.     

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.     

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.     

Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune correlates

OBJECTIVE: To determine the following: 1) whether dietary supplementation with fish oil will allow the discontinuation of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA); 2) the clinical efficacy of high-dose dietary omega 3 fatty acid fish oil supplementation in RA patients; and 3) the effect of fish oil supplements on the production of multiple cytokines in this population. METHODS: Sixty-six RA patients entered a double-blind, placebo-controlled, prospective study of fish oil supplementation while taking diclofenac (75 mg twice a day). Patients took either 130 mg/kg/day of omega 3 fatty acids or 9 capsules/day of corn oil. Placebo diclofenac was substituted at week 18 or 22, and fish oil supplements were continued for 8 weeks (to week 26 or 30). Serum levels of interleukin-1 beta (IL-1 beta), IL-2, IL-6, and IL-8 and tumor necrosis factor alpha were measured by enzyme-linked immunosorbent assay at baseline and during the study. RESULTS: In the group taking fish oil, there were significant decreases from baseline in the mean (+/- SEM) number of tender joints (5.3 +/- 0.835; P < 0.0001), duration of morning stiffness (-67.7 +/- 23.3 minutes; P = 0.008), physician's and patient's evaluation of global arthritis activity (-0.33 +/- 0.13; P = 0.017 and -0.38 +/- 0.17; P = 0.036, respectively), and physician's evaluation of pain (-0.38 +/- 0.12; P = 0.004). In patients taking corn oil, no clinical parameters improved from baseline. The decrease in the number of tender joints remained significant 8 weeks after discontinuing diclofenac in patients taking fish oil (-7.8 +/- 2.6; P = 0.011) and the decrease in the number of tender joints at this time was significant compared with that in patients receiving corn oil (P = 0.043). IL-1 beta decreased significantly from baseline through weeks 18 and 22 in patients consuming fish oil (-7.7 +/- 3.1; P = 0.026). CONCLUSION: Patients taking dietary supplements of fish oil exhibit improvements in clinical parameters of disease activity from baseline, including the number of tender joints, and these improvements are associated with significant decreases in levels of IL-1 beta from baseline. Some patients who take fish oil are able to discontinue NSAIDs without experiencing a disease flare.     

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.     

Cell mediated immunity in rheumatoid arthritis: Imparied lymphocyte responsiveness, humoral immunosuppressants, and correlations with clinical status in patients off drug therapy

Cell mediated immune functions were studied in 17 patients with rheumatoid arthritis (RA) at times off all drug therapy, and were correlated with clinical findings. Cellular immunity was evaluated by (1) skin testing to antigens and (2) measuring peripheral blood lymphocyte (PBL) and effusion lymphocyte tritiated thymidine (3H-TdR) uptake in in vitro cultures containing 20 percent autologous or 20 percent AB plasma and various concentrations of mitogens or antigens. Cutaneous and in vitro reactivity were decreased in RA patients: (1) RA PBL spontaneously incorporated more 3H-TdR than normals; (2) 3H-TdR uptake by RA PBL, cultured in AB plasma, in response to mitogens and antigens was markedly reduced when compared with normals; (3) RA PBL responses were further diminished when cells were cultured in autologous plasmas; (4) effusion lymphocytes similarly often had high unstimulated 3H-TdR uptakes and poor responses to stimulation; and (5) decreased proliferative responses of RA PBL (in AB plasma) correlated with class and stage III-IV, increasing age, number of tender or swollen joints, rheumatoid factor titer, total protein, decreased grip strength, and poor skin test reactivity.     

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.     

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.     

Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells

OBJECTIVE: To evaluate tolerability and efficacy of combination therapy with methotrexate (MTX)/parenteral gold or MTX/other disease modifying antirheumatic drug (DMARD, d-penicillamine or chloroquine) in comparison with MTX monotherapy in patients with longstanding destructive active rheumatoid arthritis (RA). METHODS: In an open prospective trial all consecutive MTX-naive patients with active RA starting MTX treatment alone or in combination between January 1980 and December 1987, after failing one or more DMARD, were followed at regular intervals up to 108 months. Evaluations included the number of swollen joints (0-32), grip strength, patient assessment of pain and mobility, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and hemoglobin. Group 1, treated with MTX monotherapy (n = 97), was compared with Group 2, with combination therapy MTX/parenteral gold (n = 126) and Group 3 with MTX + other DMARD (n = 48). RESULTS: There were no significant differences between the groups in mean age (59/57/56 yrs), disease duration (9.6/7.7/8.3 yrs), seropositivity (80/88/82%), or ACR anatomical disease stage (2/3 in stage III and IV). The number of swollen joints (16.8/19.3/16.1 of 32) and the CRP (4.4/5.1/4.7 mg/dl) was significantly greater in Group 2; other disease activity variables were not significantly different. The mean MTX dose at baseline (mostly parenteral) was 16.8/17.0/12.8 mg and could be reduced to around 12 mg (predominantly oral) in the 3 groups. Frequency of adverse events (80/83/88%), nature of clinical (nausea, hair loss, stomatitis) and laboratory (liver enzyme elevation, slight proteinuria) side effects, and withdrawal rate for side effects (20.6/15.0/12.5%) were not significantly different between the groups. After 5 years 54/54/80% of patients continued their treatment. All efficacy variables improved significantly (p < 0.001) in all groups without significant intergroup difference. Improvement > 50% in the ESR was achieved in 63/68/41% and in the swollen joint count in 70/85/48% of patients after 3 years. The number of patients taking oral steroids decreased from 63/59/65% to 22/31/48% after 3 years. In half the patients hemoglobin increased by at least 1 g/dl. CONCLUSION: Combination therapy of MTX with parenteral gold or other DMARD is effective in reducing clinical and biochemical disease activity in patients with longstanding destructive RA with no greater risk of toxicity compared with MTX alone; our study however, did not show clear advantages of combination therapy versus monotherapy for effectiveness.     

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.     

Remission induction after pentoxifylline treatment in a patient with rheumatoid arthritis

Pentoxifylline (POF) has been shown to have anti-inflammatory and immunomodulatory effects. including suppression of TNF-alpha production by activated macrophages, Th-1 response of T cells, and fibroblasts' proliferation and metalloproteinase production. Pentoxifylline was also reported to possess therapeutic properties in 50% of severe refractory RA in an open study. We experienced a 64 year-old man with seronegative RA, stage 2, class 3. He showed 23 swollen joints, 32 painful joints, ADL score 37/40, and ESR 135 mm/h. All these parameters were dramatically improved 3 weeks after administration of POF 300 mg/d and prednisolone 5 mg/d. Discontinuation of POF resulted in rapid exacerbation of RA. POF was restarted and the patient showed complete recovery from arthritis with normalization of ESR within 3 months and was maintained a complete remission for another 1 year. This case further supports a potential antirheumatic effect of POF on some patients with RA.     

Elderly rheumatoid arthritis patients on steroid treatment tolerate physical training without an increase in disease activity

The effects of physical training on elderly, fragile patients with rheumatoid arthritis (RA) who are on low-dose steroids were investigated. The controlled study included 24 patients who had been treated with low-dose steroids for 2 years. Each patient was assigned either to a treatment group receiving training or to an untrained control group. The training took place over a 3-month period and was based on a protocol using progressive interval training consisting of bicycle exercises, heel lifts, and step-climbing. The exercises were performed twice weekly for 45 minutes. Comparison of the two groups showed that disease activity did not increase in the trained group and that fewer, but not significantly fewer, swollen joints were observed in this group (p = 0.06). No significant changes were noticed in erythrocyte sedimentation rate, tender joints, or morning stiffness. The work capacity of the trained patients were doubled and the numbers of repetitions increased 76%. Individually adapted exercise programs can therefore be recommended for elderly rheumatoid arthritis patients on steroid treatment.     

Nutritional status of Danish rheumatoid arthritis patients and effects of a diet adjusted in energy intake, fish-meal, and antioxidants

This study deals with the nutritional status of Danish RA patients and address the question of whether or not RA can be directly influenced by dietary manipulation. In a prospective, single-blinded study of 6 months duration, 109 patients with active RA were randomly assigned to either treatment with or without a specialized diet. The energy consumption was adjusted to normal standards of body weights and the intake of fish meals and antioxidants were increased. A daily food diary was completed by the patients, and the total intake of 47 different food-elements was calculated. Nutritional status together with disease activity parameters were recorded. At baseline, the Danish RA-patients had neglected food habits with a significant reduction in intake of total energy, of D-vitamin and of E-vitamin. A very low intake of n-3 fatty acids was also found. During the study, 28 of the 109 patients dropped out, introducing a confounding effect on the overall result. In the remaining 81, those following the diet demonstrated a significant improvement in the duration of morning stiffness, number of swollen joints, pain status, and reduced cost of medicine, while doctors global assessment, laboratory data, X-ray, and daily activities were unaltered. In conclusion, dietary analysis and appropriate, corrective advice should be offered to Danish RA patients.     

Nutritional status of Danish patients with rheumatoid arthritis and effects of a diet adjusted in energy intake, fish content and antioxidants

This study deals with the nutritional status of Danish rheumatoid arthritis (RA) patients and addresses the question whether or not RA can be directly influenced by dietary manipulation. In a prospective, single-blinded study of six months' duration, 109 patients with active RA were randomly assigned to treatment with or without a specialized diet. The energy consumption was adjusted to normal standards for body-weight and the intake of fish and antioxidants was increased. A daily food diary was completed by the patients, and the total intake of 47 different food-elements was calculated. Nutritional status together with disease activity parameters were recorded. At baseline, the Danish RA-patients had neglected food habits with a significant reduction in intake of total energy, of D-vitamin and of E-vitamin. A very low intake of n-3 fatty acids was also found. During the study, 28 of the 109 patients dropped out, introducing a confounding effect on the overall result. In the remaining 81, those following the diet demonstrated a significant improvement in the duration of morning stiffness, the number of swollen joints, the pain status and reduced the cost of medicine, while doctors' global assessment, laboratory data, X-ray and the daily activities were unaltered. In conclusion, dietary analysis and appropriate, corrective advice should be offered to Danish RA patients.     

A double-masked comparison of Naprelan and nabumetone in osteoarthritis of the knee. Naprelan Study Group

The efficacy and safety of Naprelan (naproxen sodium) 1000 mg once daily (QD) and nabumetone 1500 mg QD were compared in a multicenter, randomized, parallel-group, placebo-controlled, double-masked, 4-week study of adult outpatients with active osteoarthritis (OA) of the knee. Nabumetone 1500 mg was chosen for comparison because it is commonly prescribed in a QD dosing regimen for OA. After a washout period free of nonsteroidal anti-inflammatory drugs, 279 patients were enrolled and assigned randomly to treatment with either Naprelan 1000 mg QD (n = 92), nabumetone 1500 mg QD (n = 93), or placebo (n = 94). All treatments were evaluated for efficacy and safety at baseline and at weeks 2 and 4 of the treatment period or at discontinuation. Demographic characteristics were comparable among all treatment groups. As might be expected in a study of OA of the knee, a majority of patients enrolled were women (68.8%), and many were obese (mean weight, 195.6 lb; mean height, 66 in). Significantly fewer patients (13) treated with Naprelan prematurely discontinued the study than did patients treated with placebo (27); there was a lower rate of discontinuation for insufficient therapeutic effect in the Naprelan group compared with the nabumetone and placebo groups. Using an intent-to-treat model, the overall distribution of scores in all three primary efficacy assessments (investigator's global assessment of OA, patient's global assessment of OA, and walking pain) at week 2 and at the last visit was significantly better for the Naprelan group compared with both the nabumetone and placebo groups. The mean improvement from baseline was also significant for Naprelan compared with the nabumetone and placebo groups for all three assessments at week 2 and for investigator's global assessment of OA and walking pain at the last visit. The nabumetone-treated group showed significant improvement over the placebo-treated group in only one primary assessment: mean change from baseline in patient's global assessment of OA at week 2. At week 2, significant differences favoring Naprelan versus nabumetone and placebo were measured in overall distribution of scores for joint tenderness and nighttime pain. Distribution of quality of sleep and inactivity stiffness scores also improved relative to placebo at week 2. At the last visit, nighttime pain scores were still significantly better for patients receiving Naprelan versus nabumetone and placebo. Patients receiving nabumetone had statistically significant improvement from baseline in inactivity stiffness compared with placebo at week 2. There were no clinically important differences among treatment groups in the occurrence of adverse events or laboratory abnormalities. The results of this 4-week study of Naprelan 1000 mg QD compared with nabumetone 1500 mg QD demonstrate at least equal efficacy (superior efficacy was demonstrated for several parameters) and equal safety in adult outpatients with active OA of the knee.