Should improvement in rheumatoid arthritis clinical trials be defined as fifty percent or seventy percent improvement in core set measures, rather than twenty percent?

OBJECTIVE: To determine whether improvement of more than 20% in core set parameters should be required before patients are characterized as improved in rheumatoid arthritis (RA) clinical trials. METHODS: Data from 6 RA trials were reanalyzed to evaluate the discriminant validity (ability to differentiate active treatment from control) of 4 proposed definitions of improvement: the current American College of Rheumatology (ACR) definition (a 20% threshold for core set parameters [ACR 201), a 50% threshold (ACR 50), a 70% threshold (ACR 70), and an ordinal definition in which a patient could be classified in any of 3 categories (unimproved, ACR 20, or ACR 50). To evaluate the discriminant validity of these 4 definitions of improvement, we characterized each patient in each trial as improved or not, based on each definition, and computed a chi-square value differentiating the active treatment group from the control group, with the corresponding P value. RESULTS: With an increase in the threshold for improvement, the percentage of placebo-treated patients who were classified as experiencing response dropped dramatically in all trials, as did the percentage of patients receiving active therapy (second-line drug, combination therapy, tumor necrosis factor p75-Fc fusion protein) who were classified as experiencing response. Generally, the drop in active treatment response rates was greater than the drop in placebo response rates, leaving the difference between the 2 groups less at the higher thresholds. Therefore, chi-square values fell as the threshold for response was raised. The ordinal definition of improvement yielded chi-square values similar to those obtained using ACR 20 alone. CONCLUSION: Adopting a definition of efficacy in RA trials that requires 50% or 70% improvement in core set parameters would likely compromise statistical power and make it more difficult to distinguish between 2 treatments with different efficacy. ACR 20 should continue to be the primary measure of efficacy in RA trials, with higher thresholds for improvement being determined and reported as secondary efficacy measures.     

Assessment of disease activity in rheumatoid arthritis using magnetic resonance imaging: quantification of pannus volume in the hands

We attempted to assess whether pannus volume measured by magnetic resonance imaging (MRI) can be used as an indicator of disease activity in rheumatoid arthritis (RA). Eleven women (mean age 46 yr) with uncontrolled RA were studied for 1 yr. Pannus formation in both hands was quantified using MRI at the start of the study, and at 6 and 12 months thereafter. The volume of enhancing pannus (VEP) was compared with changes in the radiological scores, grip strength, joint tenderness counts, joint swelling counts, erythrocyte sedimentation rate (ESR), and serum C-reactive protein (CRP). Patients were classified into three groups based on VEP changes between 0 and 12 months: unchanged (n = 2), decreased (n = 6) and increased (n = 3). VEP at 6 months and at 12 months differed significantly between the three groups. No statistically significant differences were found between the groups in radiographic scores, physical parameters or laboratory parameters despite the fact that some of these parameters changed in the direction indicated by the changes in VEP. VEP can be used as a new indicator to assess disease activity in individual RA patients and, using this parameter, treatment outcome can be assessed in fewer subjects than with traditional measures.     

A proposed 30-45 minute 4 page standard protocol to evaluate rheumatoid arthritis (SPERA) that includes measures of inflammatory activity, joint damage, and longterm outcomes

A proposed 4 page, 30-45 minute standard protocol to assess rheumatoid arthritis (SPERA) is described that includes all relevant measures of inflammatory activity such as joint swelling, measures of joint damage such as joint deformity, and outcomes such as joint replacement surgery, to monitor patients in longterm observational studies. Forms are included: (1) a patient self-report modified health assessment questionnaire (MHAQ) to assess function, pain, fatigue, psychological distress, symptoms, and drugs used; (2) assessor-completed forms: "RA clinical features" --criteria for RA, functional class, family history, extraarticular disease, comorbidities, joint surgery, radiographic score, and laboratory findings. (3) A 32 joint count with 5 variables: (a) a "shorthand" normal/abnormal so that normal joints require no further detailed assessment; (b) tenderness or pain on motion; (c) swelling; (d) limited motion or deformity; (e) previous surgeries; physical measures of function, i.e., grip strength, walk time, and button test. (4) Medication review of previous disease modifying antirheumatic drugs (DMARD), work history, and years of education. The forms allow cost effective acquisition of all relevant measures of activity, damage, and outcomes in routine clinical care, and allow recognition that measures of activity may show similar or improved values over 5-10 years, while measures of damage and outcomes indicate severe progression in the same patients. The SPERA is feasible to acquire most known relevant measures of activity, damage, and outcomes in RA in 30-45 min in usual clinical settings, to provide a complete database for analyses of longterm outcomes.     

Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers

OBJECTIVE: To investigate whether plasma levels of matrix metalloproteinases 3 (MMP-3, stromelysin), MMP-1 (collagenase), tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP1/TIMP-1 complex (MT complex) are specifically elevated in erosive joint diseases compared to nonerosive rheumatic diseases, and to assess how these markers reflect the clinical activity of rheumatoid arthritis (RA) compared to circulating cytokines and markers of connective tissue turnover as well as established variables [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor titer]. METHODS: Plasma levels of MMP-3, MMP-1, TIMP- 1, and MT complex were determined by ELISA. One hundred fifteen patients with RA, 20 with osteoarthritis (OA), 28 with psoriasis arthritis (PsA), 24 with ankylosing spondylitis (AS), 3 groups with systemic autoimmune diseases, and 30 healthy controls were analyzed. In patients with RA routine laboratory variables, circulating inflammatory cytokines [interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-6], collagen degradation products, and markers of bone formation were determined in parallel and were correlated to 4 variables of clinical activity. RESULTS: MMP-3 levels were markedly elevated in RA compared to controls and OA, but also in all other groups, including 26 patients with systemic lupus erythematosus (SLE). MMP-1 levels were significantly elevated in RA, but also in OA, PsA, SLE, and mixed connective tissue disease. In contrast, MT complex was elevated in RA only. TIMP-1 was not different from controls. CRP levels, MMP-3, and ESR correlated best with clinical activity of RA. In contrast, there was no correlation of IL-1 and TNF-alpha and only a weak correlation of IL-6 with clinical measures. Among variables of connective tissue turnover, only pyridinoline and deoxypyridinoline crosslinks were weakly correlated with disease activity. CONCLUSION: Elevated MMP-3 and MMP-1 levels are not specific for RA or for erosive joint diseases in general. In contrast, elevated MT complex levels were observed in patients with RA. However, the correlation of MT-1 with clinical data was weaker than that of MMP-3. Elevated MMP-3 levels reflected disease activity of RA better than cytokine levels or markers of connective tissue turnover. However, MMP-3 levels do not exceed the association of CRP with clinical activity.     

Only high disease activity and positive rheumatoid factor indicate poor prognosis in patients with early rheumatoid arthritis treated with "sawtooth" strategy

OBJECTIVES: To investigate the prognostic significance of clinical and genetic markers on the outcome of patients with recent-onset rheumatoid arthritis (RA) treated actively with slow acting antirheumatic drugs (SAARDs). METHODS: A total of 142 consecutive patients with early RA (median disease duration of 7 months) were treated according to the "sawtooth" strategy and prospectively followed up for an average of 6.2 years. Several clinical parameters at start as well as genetic markers were related to the functional outcome (ARA Functional class and HAQ disability score) and radiographic joint damage (Larsen's score) at the latest visit. RESULTS: In logistic regression analysis only Mallya score (including morning stiffness, pain scale, grip strength, Ritchie's articular index, haemoglobin, and erythrocyte sedimentation rate) at baseline, and Mallya score and rheumatoid factor (RF) positivity at one year were found to be of significance with respect to the radiographic outcome of the patients. Furthermore, at the latest visit HAQ score was related to radiographic score. At baseline the mean ages of the DR4 positive patients and the patients with RA associated DR alleles were statistically significantly lower than those without the above mentioned risk factors (44 v 49, p = 0.03 and 41 v 53, p = 0.04, respectively). However, these genetic markers had no prognostic significance on the functional or radiographic outcome of the patients. CONCLUSION: High clinical disease activity at baseline and RF positivity especially at one year after the institution of SAARD treatment are the best predictors of poor prognosis in early RA. However, from the clinical point of view, the disease outcome of an individual patient with early RA, cannot be predicted accurately enough by present means.     

Salsalate, a nonacetylated salicylate, is as efficacious as diclofenac in patients with rheumatoid arthritis. Salsalate-Diclofenac Study Group

OBJECTIVE: To investigate the efficacy of salsalate, a nonacetylated salicylate, in the treatment of patients with rheumatoid arthritis (RA). METHODS: Three hundred and one patients meeting the ACR criteria for RA were drawn from 16 centers. After withdrawal of nonsteroidal antiinflammatory drugs (NSAID) and subsequent flare, patients were randomized to receive either salsalate or diclofenac for 8 weeks, according to a double blind, double dummy protocol. Initial doses of salsalate 3.0 g/day and diclofenac 75 mg/day were titrated for the first 5 weeks. The primary outcome measure was a multivariate analysis at 8 weeks of tender joint count, pain, visual analog scale score, and physician's global assessment. RESULTS: One hundred and ninety patients completed the study. The mean stabilized dose of salsalate was 3.55 g/day, and that of diclofenac 112 mg/day. Discontinuations were due to lack of efficacy (17 salsalate vs 15 diclofenac); adverse events [19 salsalate (mainly tinnitus and hearing loss; p = 0.0001 and p = 0.04, respectively) vs 9 diclofenac]; laboratory abnormalities (3 salsalate vs 1 diclofenac); and other reasons, including protocol violations, intercurrent illness, and personal factors (24 salsalate vs 23 diclofenac). Both treatments produced significant improvement from flare (p < 0.0001). Post hoc power analysis showed that the study had sufficient power (0.60 to 0.90) to detect clinically important differences between the 2 drugs in the primary outcome measures; however, no statistically significant (p = 0.29) or clinically important treatment differences were recorded. Other than a difference in erythrocyte sedimentation rate that favored salsalate, there were no significant differences in secondary outcome measures between the 2 groups. All outcomes showed a tendency for more improvement with salsalate. CONCLUSION: Salsalate is as efficacious as diclofenac. Salsalate may be considered an alternative to other NSAID in the first line treatment of patients with RA.     

The levels of memory (CD45RA-, RO+) CD4+ and CD8+ peripheral blood T-lymphocytes correlate with IgM rheumatoid factors in rheumatoid arthritis

We investigated whether, in rheumatoid arthritis (RA), the CD45 isoform expression of peripheral blood T-lymphocytes (T-PBL) is related to auto-immune processes (e.g. IgM rheumatoid factors) and to clinical manifestations. By three-colour flow cytometry, we quantified three subsets of CD4+ or CD8+ T-PBL: "naive" CD45RA+,RO-, "transient" CD45RA+,RO+, and "memory" CD45RA-,RO+ cells, in 102 patients with RA and in 41 age- and sex-matched controls. The serum levels of rheumatoid factors (RF) were determined--besides conventional agglutination tests--by ELISA (IgM-RF). Extensive clinical examination was performed at the time of blood sampling. In RA, age, sex and drug therapy did not constitute major influences on the CD45RA/RO patterns. In "healthy" men, higher age significantly' correlated with fewer naive and more memory CD4+ T-PBL (P < 0.01). In RA, distinct correlations between the T-PBL subsets, autoimmune and clinical manifestations became obvious when patients with low and high levels of RF against human IgG Fc fragments, as determined by ELISA, were analysed separately. RA patients with high IgM-RF had elevated proportions of CD45RO+ T-PBL (P < 0.05), that correlated with clinical parameters of disease activity (tender joint count, Ritchie index, P < 0.05) and outcome (Health Assessment Questionnaire, Larsen radiographic scores, P < 0.05). The proportions of memory CD4+ and CD8+ T-PBL correlated strongly (P < 0.001) with the IgM-RF levels. Within 1 year, only three of 34 patients (disease duration of 5-9 years) showed seroconversion from low to high levels of IgM-RF (and positive agglutination tests); this was paralleled by reductions in naive and increases in transient T-PBL (P < 0.02). Thus, in RA, the proportions of memory CD4+ and CD8+ T-PBL correlate with the level of IgM-RF and, together with transient T-PBL, with clinical parameters of disease activity and outcome.     

Epidemiologic and actual importance of entero-hemorrhagic E. coli in Northern Bavaria (1996)

OBJECTIVES: To compare peripheral type 1 (T1) and type 2 (T2) T cell activities in rheumatoid arthritis (RA) patients with that found for osteoarthritic (OA) patients and healthy controls and to correlate peripheral T1/T2 cell activity in RA with parameters of the disease. METHODS: Peripheral blood mononuclear cells were isolated from patients with RA (n = 66), OA (n = 19), and healthy controls (n = 15). Primary T cell activity in these mononuclear cells was enhanced by means of anti-CD3/anti-CD28, which mimicks stimulation of T cells by activation of the T cell receptor and a major co-stimulatory signal. Interferon gamma (IFN gamma) production and interleukin 4 (IL4) production in the three groups were quantified as measures of T1 and T2 cell activity, respectively, and compared. Serum tumour necrosis factor alpha (TNF alpha), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and joint destruction assessed radiographically of RA patients were determined as parameters of disease activity and correlated with T1/T2 cell activity. RESULTS: Peripheral T cells from RA patients produced significantly less IFN gamma and more IL4 than T cells from both age and sex matched OA patients and healthy controls. Moreover, in RA patients both a decrease in IFN gamma and an increase in IL4 production correlated with an increase in serum TNF alpha, ESR, CRP, and joint destruction. CONCLUSIONS: These results suggest a role for differential T cell activity in RA. In view of the intra-articular T1 cell predominance the results might be explained by selective T1 cell migration into the joint or peripheral suppression of T1 cell activity.     

Clinical associations of dual-energy X-ray absorptiometry measurement of hand bone mass in rheumatoid arthritis

Hand bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) has potential as a marker of progression in early rheumatoid arthritis (RA). We examined a DXA methodology and studied in a cross-sectional manner 202 patients with RA. Hand BMD correlated inversely with age and was higher in males. Hand BMD correlated with lumbar and femoral sites. In females, BMD of the hand correlated positively with grip strength and negatively with disability. Those with higher C-reactive protein (CRP) had significantly lower hand BMD than those with normal CRP. In patients with a normal CRP, the hand BMD:lumbar BMD ratios were significantly higher in patients with longer disease duration. Hand BMD correlates with measures of disease activity, functional capacity and also with lumbar and femoral BMD. Hand bone loss occurs in early disease, in the absence of detectable systemic disease, and before lumbar BMD loss. It has the potential to be an outcome measure in early disease.     

Cyclosporine A in the treatment of early rheumatoid arthritis. A prospective, randomized 24-month study

OBJECTIVE: To investigate the efficacy, tolerability and safety of cyclosporine A (CSA) in early rheumatoid arthritis (RA) patients. METHODS: Patients with an early diagnosis of RA, a disease duration of less than 3 years, and without prior disease modifying antirheumatic drug (DMARD) treatment were studied. They randomly received oral CSA (3 mg/kg/day) or oral methotrexate (MTX) (0.15 mg/kg/week). In addition, all patients in both groups received oral prednisone (7.5 mg/day). RESULTS: Fifty-two patients were assigned to the CSA group and 51 to the MTX group. After 24 months of treatment, 48 patients from the CSA group and 48 from the MTX group showed significant clinical improvement. This was evaluated by the duration of morning stiffness, grip strength, the total joint count, joint swelling, and joint tenderness and pain, compared to pre-treatment values. The clinical improvement was also associated with a significant decrease in ESR and CRP values in both groups. No significant radiological deterioration was observed in the CSA patients compared to those treated with MTX after 24 months. Four patients from the CSA group dropped out of the study, two because of a synovitis flare, one because of severe hypertrichosis and one because of severe gingival hyperplasia. Three patients from the MTX group withdrew, one because of disease flare-up and two because of gastrointestinal disturbances. CONCLUSION: Early immunointervention in RA patients appears to be crucial to limit the development of joint damage. Cyclosporine A appears to be effective, well tolerated and safe in the long-term treatment of RA and can therefore be used as a first immunomodulatory drug in the armamentarium for the treatment of 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.     

Measures of disease activity and damage in SLE

Criteria for the classification of systemic lupus erythematosus (SLE) are not sufficient to describe the degree of disease activity. Several instruments to assess disease activity have been developed. This chapter reviews the derivation, validation, and clinical application of current disease activity measures in SLE, as well as comparison among them. As patients with lupus survive longer, the sequelae of the disease activity and its therapy are becoming more common. The derivation and validation of the single, generally accepted SLICC/ACR damage index is also discussed.     

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.     

Clinical improvement and radiological deterioration in rheumatoid arthritis: evidence that the pathogenesis of synovial inflammation and articular erosion may differ

The contrast between clinical improvement and radiological deterioration in rheumatoid arthritis (RA) is striking. We characterized this relationship using serial disease activity measures and radiographs of hands and feet in 40 RA patients observed over 6 yr. All disease activity measures improved, including grip strength, Ritchie index (RI), haemoglobin and erythrocyte sedimentation rate (ESR) (all P < 0.0001). In contrast, articular erosion increased (P < 0.0001). Radiological change during the study correlated with RI (r = 0.49), haemoglobin (r = -0.56) and ESR (r = 0.53). Radiological status at review also correlated with these variables (r = 0.36, -0.44 and 0.36, respectively). Articular erosion continues in RA despite clinical improvement and is accelerated in those with evidence of continuing synovial inflammation, reflected in clinical and laboratory measures of disease activity. Since many therapies in RA suppress inflammation, but not erosion, these findings suggest that the pathogenesis of articular erosion may differ from that of synovial inflammation.     

Outcome measures to be used in clinical trials in systemic lupus erythematosus

The optimal outcome measures to be employed in clinical trials of systemic lupus erythematosus (SLE) have yet to be determined. Useful instruments should assess disease outcome in terms of all organ system involvement, as well as measures important to the patient. This article reviews those outcome measures that have been utilized in cohort studies in SLE, as well as their limited use in randomized clinical trials (RCT). Six disease activity measures have been developed: British Isles Lupus Assessment Group Scale (BILAG), European Consensus Lupus Activity Measure (ECLAM), Lupus Activity Index (LAI), National Institutes of Health SLE Index Score (SIS), Systemic Lupus Activity Measure (SLAM), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). They have been validated in cohort studies as reflecting change in disease activity, and against each other. RCT utilizing SLAM, SLEDAI, BILAG, ECLAM, SIS, SLAM, SLEDAI are ongoing. It is recommended that the disease activity index of choice be selected; but simultaneous computer generation of multiple indices will facilitate comparisons across therapeutic interventions. A damage index has been developed and validated as the Systemic Lupus International Cooperating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index or SDI. In several cohort studies it has been shown sensitive to change over time, and to reflect cumulative disease activity. There is no health status or disability instrument specific to SLE. The Medical Outcomes Survey (SF-20) captures health status/health related quality of life (HRQOL) better than the Health Assessment Questionnaire (HAQ) in patients with SLE, but does not adequately reflect fatigue. The SF-36 does assess fatigue, and correlates closely with the SF-20. These data indicate that any individual measure of clinical response to a therapeutic intervention in SLE may reflect only a portion of what might be termed the "true outcome." Based on this work, the way is now paved to attempt to develop consensus on the important domains to be measured in clinical trials in SLE, the most appropriate instruments to use and the minimal clinically important differences in their results.     

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.     

Activation of the haemostatic system in children with juvenile rheumatoid arthritis correlates with disease activity

Twenty-four children with juvenile rheumatoid arthritis (JRA) and 10 children with postinfectious arthropathies were investigated for markers of blood coagulation and fibrinolytic activity: Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and D-Dimer were measured using solid phase enzyme linked immunosorbent assays (ELISA). Results were compared with clinical and conventional laboratory signs of disease activity. F1+2, TAT, D-Dimer, and fibrinogen were significantly elevated in children with JRA as compared with healthy children and children with postinfectious arthropathies. F1+2, TAT, and D-Dimer correlated significantly with disease activity, assessed by determination of the joint index score and C-reactive protein (CRP). The study demonstrates a subclinical activation of the haemostatic system in children with JRA correlating with disease activity, which might be caused by the action of several immunomediators on cells (monocytes, endothelial cells) playing a role in the regulation of blood coagulation activity.     

A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis

Fish oil may be beneficial in the treatment of psoriasis and in RA. We examined the potential benefit of Efamol Marine, a combination of evening primrose oil and fish oil in the treatment of 38 patients with PsA. Patients with PsA were entered in a double-blind placebo controlled study and received either 12 Efamol Marine capsules or 12 placebo capsules daily for 9 months. All patients received placebo capsules for a further 3 months. At month 3 of the study patients were asked to reduce their intake of NSAIDs and maintain that decrease provided there was no worsening of their joint symptoms. Clinical assessments of skin and joint disease severity and activity were performed at 0, 1, 3, 6, 9 and 12 months. All measures of skin disease activity including severity, percentage body affected and itch were unchanged by Efamol Marine. The NSAID requirement remained the same between both treatment groups. In addition, there was no change demonstrated in the activity of arthritis as measured by duration of morning stiffness. Ritchie articular index, number of active joints, ESR and CRP. However, a rise in serum TXB2 was observed in the active group during the placebo phase; in addition a fall in leukotriene B4 production occurred during the active phase period followed by a marked rise during the placebo phase suggesting some laboratory documented anti-inflammatory effect. In conclusion, this study suggests that Efamol Marine may alter prostaglandin metabolism in patients with PsA, although it did not produce a clinical improvement and did not allow reduction in NSAID requirement. A larger dose of essential fatty acid may be needed to produce a clinical benefit.     

Differential relationships between stress and disease activity for immunologically distinct subgroups of people with rheumatoid arthritis.

Immunologically distinct subgroups of patients with rheumatoid arthritis (RA)--those with the autoantibody rheumatoid factor (seropositive RA) and those without (seronegative RA) were compared on a variety of clinical and self-report measures in a consecutive series of women with disease of 7 yrs or less duration. The groups were comparable on clinical, pain, functional, and psychosocial variables. However, the seronegative RA group reported elevated levels of pre-onset negative life event stress. Postonset life event stress and disease activity were significantly correlated for the seronegative RA group, but not for the seropositive RA group. Results suggest that stress factors may be more important in the etiology and maintenance of seronegative RA and that the seronegative RA group may possibly derive particular benefit from psychological techniques to enhance stress management skills. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of 3 quantitative measures of hand radiographs in patients with rheumatoid arthritis: Steinbrocker stage, Kaye modified Sharp score, and Larsen score

OBJECTIVE: To compare 3 quantitative hand radiograph scores, Steinbrocker stage, Larsen score, and Sharp score modified by Kaye, to one another and to other measures of clinical status in a cross sectional analysis of hand radiographs of 173 patients with rheumatoid arthritis (RA). METHODS: Radiographs were scored and compared to other measures of clinical status according to correlation and cross tabulation analyses. RESULTS: In these cross sectional studies, radiographic scores according to all 3 methods were correlated at high levels (r(s) > 0.5) with one another and duration of disease, as well as with scores for physical joint deformity and limited motion; at lower levels (0.3 < r(s) < 0.5) with physical joint swelling scores, functional status, and age; and at low levels of marginal or no clinical importance (r(s) < 0.3) with physical joint tenderness scores, laboratory data, and pain scores. CONCLUSION: The 3 scoring methods give similar quantitative information concerning hand radiographs of patients with RA. The Larsen and modified Sharp scores are preferred measures, as the detailed information facilitates comparison of different patients and monitoring of individual patients over time.