Disease activity and joint damage progression in early rheumatoid arthritis: relation to IgG, IgA, and IgM rheumatoid factor.

The clinical and biochemical correlations with joint damage progression over two years in a consecutive group of 68 patients with rheumatoid arthritis with disease duration of less than two years are reported. Joint damage was assessed with Larsen's severity scale and a measure of change in progression rate constructed. Initial haemoglobin concentration, Ritchie index, and Waaler-Rose titre in combination accounted for one third of the variance in joint damage progression. Rheumatoid factor (RF) concentrations were followed with enzyme linked immunosorbent assays (ELISAs) for IgG RF, IgA RF, and IgM RF. The RF concentrations, except IgG RF, decreased with time; significant correlations between RFs and disease activity were few and barely clinically useful. After two years IgG RF correlated significantly with a radiological score if early non-erosive changes were omitted. All RFs tended to correlate better with this radiological score at all three observation points. Analyses of the change in progression rate indicated a time delay between development of radiographic changes and increase of IgG RF. These results suggest an indirect relation between RFs and joint damage. Clinical and biochemical improvements in early RA occur despite joint damage progression, and conventional markers have insufficient predictive value.     

Interleukin 10 (IL-10), not IL-4 or interferon-gamma production, correlates with progression of joint destruction in rheumatoid arthritis

OBJECTIVE: Both interleukin 4 (IL-4) and IL-10, separately and in combination, and under in vitro and in vivo conditions in animals, have been reported to inhibit characteristics of rheumatoid arthritis (RA) and experimentally induced arthritis. We investigated if IL-10 and IL-4 production, as well as interferon-gamma (IFN-gamma) production, opposing IL-4, were related to RA disease variables. A method was chosen to exclude the influence of age and disease duration. METHODS: We selected RA patients with mild and severe disease. Inclusion criteria were erythrocyte sedimentation rate (ESR) < or = 28 mm/h and > or = 50, C-reactive protein (CRP) < or = 20 and > or = 30, Thompson joint score < or = 60 and > or = 100 and radiographic joint damage score, Sharp score < or = 30 and > or = 40. Age and disease duration were restricted: 30 to 70 years and 5 to 15 years, respectively. Peripheral blood mononuclear cells were isolated and the ex vivo 48 h production of T cell IL-10, IL-4, and IFN-gamma (after CD3-CD28 stimulation) was assessed and was correlated to clinical variables. RESULTS: Only IL-10 production differed significantly between the 2 groups of RA patients, being highest in the "mild" group. Taking all patients together, a strong negative correlation was found between IL-10 production and radiographic joint damage (r = -0.53, p < 0.001) as well as progression of joint damage (r = -0.56, p < 0.0001). Similar negative correlations, although less powerful, were found between IL-10 production and ESR, CRP, and Thompson joint score. No correlation was found for IFN-gamma, IL-4, or the ratio of the 2 with disease activity variables or joint damage. CONCLUSION: The findings suggest that the high IL-10 production found in patients with RA may be protective, especially against progression of joint destruction in RA.     

T cell proliferative response to type II collagen in the inflammatory process and joint damage in patients with rheumatoid arthritis

OBJECTIVE: To investigate the role of T cell responses to type II collagen (CII) in disease progression in patients with rheumatoid arthritis (RA). METHODS: T cell proliferative responses to bovine CII by peripheral blood mononuclear cells (PBMC) from patients with early RA (duration < 5 yrs) were assayed by mixed lymphocyte culture. Clinical and laboratory variables including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were examined at the time of sampling. Radiographic damage on hand radiographs was evaluated by the method of Steinbrocker and Sharp. RESULTS: In a cross sectional study, patients (n = 22) with positive T cell responses (stimulation index 2) had higher levels of CRP and ESR than those (n = 21) not showing T cell responses. The number of damaged joints (by Steinbrocker's method) and damaged joint scores (by Sharp's method) were significantly higher in patients with positive T cell responses than in those without. The joint space narrowing scores correlated well with T cell responsiveness to CII. Patients (n = 15) with both positive T cell responses and RA-susceptible allotypes HLA-DR1 or DR4 had higher damaged joint scores than the remainder of the patients (n = 24). CONCLUSION: T cell proliferative responses to CII are associated with inflammatory activity and radiographic severity in RA. RA-susceptible allotypes positively relate to the radiographic progression associated with T cell responses to CII. Our data suggest that CII-reactive T cells may play a role in the pathogenic process of joint damage, especially in genetically susceptible patients.     

Predictors of radiographic joint damage in patients with early rheumatoid arthritis

OBJECTIVE: To determine factors at diagnosis, associated with radiographic damage at diagnosis and after one year, in patients with early rheumatoid arthritis (RA). METHODS: New patients with early RA were followed up for one year. Possible prognostic factors were duration of complaints, morning stiffness, disease activity score (DAS28), functional status (Health Assessment Questionnaire (HAQ) score), rheumatoid factor (IgM RF), and C reactive protein (CRP). Outcome was defined as radiographic damage of the hands and feet (Sharp/van der Heijde score). For the statistical analysis, one way analysis of variance and a forward stepwise logistic regression model was used. RESULTS: 130 patients with RA (68% female; median age 64 years, range 21-86) were included. Despite the fact that the median duration of complaints was short (15 weeks, range 2-106) the radiographic damage at diagnosis was significantly correlated with the duration of complaints (p<0.05). Patients with a duration of complaints of >34 weeks had significantly more radiographic joint damage at diagnosis than patients with a shorter duration of complaints. Radiographic progression at one year was correlated with high radiographic joint damage, high CRP level, and a positive IgM RF at entry. CONCLUSIONS: In early RA, the number of radiographic lesions was correlated with a longer duration of complaints at the first visit. Progression of these lesions was predicted by a high baseline joint damage, high CRP level, and a positive IgM RF. Further reduction of the delay in referral and early treatment may further decrease joint damage in patients with recent onset polyarthritis.     

Radiological progression of joint damage in a longitudinal cohort of early DMARD-treated rheumatoid arthritis patients followed for 10 years

OBJECTIVE: The efficacy of DMARD therapy in rheumatoid arthritis (RA) can be judged by radiological analysis. This study aimed to determine the time-dependent progression of joint damage, acute-phase response, and rates of radiologic progression in early DMARD-treated RA patients over 10 years. PATIENTS AND METHODS: We evaluated outpatient records, and radiographs of hands and feet of 54 early RA patients on DMARDs for 10 years. Radiographs were quantified by the Larsen method using recently developed quantification software. RESULTS: Radiological damage attenuated, with disease progression from baseline to Year 10 [correlation coefficient (r)=0.95, probability (p)<0.001]. Radiographic scores progressed more rapidly during the first 5 years than thereafter. Cumulative erythrocyte sedimentation rate (ESR) was strongly correlated with radiological progression (p<0.001, r=0.88). CONCLUSION: Our findings reveal a higher amount of radiographic RA progression during the first years of DMARD treatment. Thus, our data provide strong evidence for the importance of both early DMARD therapy and continuous radiographic assessments in RA.     

The relationship between serum levels of YKL-40 and disease progression in patients with early rheumatoid arthritis

YKL-40 concentrations in serum were determined by an ELISA at 3 occasions during 19 months for 57 early RA patients. The results were related to biochemical and radiographic measures at each time point. YKL-40 correlated significantly to ESR and CRP throughout the study. Correlations between YKL-40 and radiographic findings scored by the Larsen method were fairly weak both for absolute values at each time point (Rs 0.212-0.319) and for progression over time (Rs 0.152-0.301). Baseline YKL-40 could predict radiographic progression with a specificity and sensitivity of only slightly over 50%. ESR and CRP correlated stronger than YKL-40 to joint damage progression and in a multiple regression model ESR was the only significant variable explaining the variance of this radiographic measure. We conclude that serial measurements of serum YKL-40 did not provide information that could not be obtained by conventional biochemical measures of disease activity.     

Relation between body mass index and radiological progression in patients with rheumatoid arthritis

OBJECTIVE: To determine if there is an influence of body mass index (BMI) on the radiological progression in early and longer duration rheumatoid arthritis (RA). METHODS: Fifty-four patients with RA were observed in a progressive 2 year followup for radiological progression of joint damage. At the beginning of study, 27 (50%) patients had a duration of complaints less than 6 months, grouped as early RA. BMI at the beginning and end of the study were monitored, together with HLA-DRB1 alleles, initial joint erosions, duration of disease, age, sex, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Outcome was defined as radiographic damage according to yearly increase of Larsen score. RESULTS: Increased radiographic joint damage of patients was significantly correlated with lower BMI at the beginning of the study (r = 0.363, p < 0.05), the presence of initial joint erosions (r = 0.341, p < 0.01), ESR (r = 0.315, p < 0.05), and CRP at study entry (r = 0.427, p < 0.01). Patients with an increase of Larsen score > or = 5.8/year were found to have a lower weight at the beginning of their complaints (BMI 24.8 +/- 4.7 vs 27.8 +/- 3.8; p < 0.05) as well as after the time of observation (BMI 24.6 +/- 3.7 vs 27.6 +/- 4.9; p < 0.05). Stepwise logistic regression analysis revealed a BMI < 27 at the beginning of disease (beta = 2.04, p = 0.003, odds ratio = 7.69), the presence of HLA-DR4 shared epitope (beta = 1.76, p = 0.015, OR 5.82), and joint erosions at study entry (beta = 1.56, p = 0.044, OR 4.78) as significant predictors for rapid joint damage. CONCLUSION: Together with the presence of HLA-DR4 shared epitope and erosive disease at study entry, a low BMI at the beginning of RA was found in association with higher radiographic progression in RA. Accordingly, BMI could be of interest as a sensitive and inflammation-independent predictor for radiological outcome of RA.     

Inflammatory patterns in rheumatoid arthritis estimated by the number of swollen and tender joints, the erythrocyte sedimentation rate, and hemoglobin: longterm course and association to radiographic progression

OBJECTIVE: To investigate the association of individual plots and time-integrated values of repeated measures of inflammatory variables with radiographic outcome in rheumatoid arthritis (RA). METHODS: In 112 patients with RA, examinations of joint swelling and joint tenderness of 68 joints, and measurement of hemoglobin (Hb) and erythrocyte sedimentation rate (ESR) were performed each year for up to 22 years after the first visit. For each of these 4 variables, the patients were divided arbitrarily into 5 characteristic subgroups by means of inspection of individual plots of longitudinal observations of the variables and divided into 5 other subgroups according to 20% percentiles of the cumulative mean values of the variables. The outcome of the subgroups was evaluated by varying degrees of radiographic events estimated by Larsen scoring of consecutive radiographs of 46 joints. RESULTS: An increasing number of radiographic events in subgroups with increasing severity (increasing values of joint swelling, joint tenderness, and ESR, decreasing values of Hb) was seen for both the arbitrary subgroups and the percentile subgroups of joint swelling, Hb, and ESR, whereas the association of joint tenderness to radiographic progression was weak. CONCLUSION: A highly significant association between inflammatory variables and radiographic outcome could be observed, indicating that the degree of inflammation is important for the development of destructive joint damage in RA.     

Interleukin 1 beta, hand and foot bone mineral content and the development of joint erosions in rheumatoid arthritis.

OBJECTIVE--To assess the relationship between plasma levels of the cytokine interleukin-1 beta (IL-1 beta) and the progression of rheumatoid arthritis (RA). METHODS--Two subgroups of patients, one with persistently raised ESR (>/= 50 mm/hour, n = 16, group A) and one with persistently low ESR (</= 28 mm/hour), n = 18, group I) were chosen to represent stable extremes of inflammatory activity from a prospective study of 106 patients with active RA studied over one year in a single centre. The change from baseline in hand, foot and calcaneal bone mineral content measured by single photon absorptiometry and radiographic score of joint damage was measured over 12 months, together with plasma IL-1 beta and erythrocyte sedimentation rate. RESULTS--Significant progression of joint damage occurred in both subgroups over one year (p < 0.0001, paired t test) though progression was significantly less in the subgroup with low ESR (p < 0.05, ANOVA). Hand and foot bone mineral content decreased by almost 10% in the subgroup with raised ESR (p < 0.005, paired t test). Stepwise linear regression analysis revealed significant independent relationships between radiographic progression over one year and plasma IL-1 beta and ESR (multiple R 0.674, F = 11.64, p < 0.0002). No such relationships were observed for changes in bone mineral content parameters. CONCLUSIONS--Plasma IL-1 beta levels correlate weakly with progression of joint damage though not with loss of peripheral bone density in RA. A significant reduction in peripheral bone mineral content occurs over one year in patients with active RA with persistently raised ESR.     

Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis

OBJECTIVE: To investigate development of radiographic damage in hands and feet of patients with early rheumatoid arthritis (RA) monitored prospectively for 10 years, and to search for prognostic factors. PATIENTS AND METHODS: 181 patients with early RA (mean disease duration one year) were assessed annually with radiographs of hands and feet during years 0-5 and at year 10. Radiographs were evaluated according to Larsen (range 0-200). Predictive factors for progressive disease for years 0-5 and 5-10 were evaluated by logistic regression analyses. RESULTS: 82/168 (49%) patients had erosions at inclusion and almost all became erosive with time (90% after two years and 96% after 10 years). Radiographic progression was most rapid during the first two years and 75% of all damage occurred during the first five years. The median Larsen score increased from 6 at inclusion to 41 after five years and 54 after 10 years. Only 5.3% of all evaluated joints became maximally eroded, the second metacarpophalangeal joint being the most commonly affected. Mean ESR during the first three months and rheumatoid factor status were significant predictors for radiographic progressive disease, it was not possible to predict non-progressive disease. CONCLUSIONS: Joint damage in hands and feet developed early and progression was most rapid during the first years of disease. The different rates of progression at different stages should be considered in the design of trials of drugs aimed at retarding joint damage. Disease activity at study start influenced the degree of joint damage during the entire 10 years.     

Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial

OBJECTIVE: To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis (RA) treated with methotrexate (MTX) versus those treated with infliximab plus MTX. METHODS: Patients who had not previously been treated with MTX with active RA were randomly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Radiographic joint damage was assessed using the modified Sharp/van der Heijde score (SHS). The relationship between disease activity measures at baseline and week 14, as well as those averaged over time, were examined in relation to the change in SHS from baseline through week 54. RESULTS: C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint count were associated with greater joint damage progression in the MTX-only group, while none of these parameters was associated with progression in the infliximab plus MTX group. Mean changes in SHS among patients in the highest CRP (> or = 3 mg/dl) and ESR (> or = 52 mm/hour) tertiles in the MTX-only group were 5.62 and 5.89, respectively, compared with 0.73 and 1.12 in the infliximab plus MTX group (P < 0.001). Patients with greater joint damage at baseline (SHS > or = 10.5) showed less progression with infliximab plus MTX compared with MTX alone (-0.39 versus 4.11; P < 0.001). Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab. CONCLUSION: High CRP level, high ESR, or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone, while little radiographic progression was seen in patients receiving both MTX and infliximab, regardless of the abnormal levels of these traditional predictors.     

Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study

OBJECTIVE: To determine prognostic factors of radiologic damage and radiologic progression in early rheumatoid arthritis (RA). METHODS: A cohort of 191 patients with RA whose disease duration was shorter than 1 year were prospectively followed up for 3 years. Radiologic scores (as determined by Sharp's method, modified by van der Heijde) and radiologic progression were used as outcome measures. Numerous baseline clinical, laboratory, genetic, and radiographic data were obtained. RESULTS: The change in the total radiologic score for the patients followed up over 3 years was a mean +/- SD increase of 6.1 +/- 6.2. Radiologic progression was observed in 71 of the 172 patients for whom there were data at the end of the study. By univariate analysis with Fisher's exact test, radiologic scores and progression at followup were closely correlated with the baseline values of the erythrocyte sedimentation rate (ESR), C-reactive protein level, IgM and IgA rheumatoid factor positivity, antiperinuclear antibody positivity, radiologic scores, duration of morning stiffness, and RA-associated HLA-DRB1*04 genes. No correlation was demonstrated with sex, age, Disease Activity Score, swollen or tender joint counts, extraarticular manifestations, Health Assessment Questionnaire score, Ritchie Articular Index, patient's assessment of pain, positivity for anti-heat-shock protein 90-kd antibodies, anticalpastatin antibodies, anti-RA33 antibodies, antinuclear antibodies, YKL-40, or antikeratin antibodies, and HLA-DRB1*01 genes. The logistic regression analysis revealed that the only baseline values that were predictive of the 3-year radiologic scores were IgM rheumatoid factor positivity, DRB1*04 genes, pain score, and total radiologic score. Progression of joint damage was predicted by the ESR, IgM rheumatoid factor positivity, DRB1*04 genes, and erosions score at baseline. CONCLUSION: Prognostic factors for radiographic damage in early RA were identified. A combination of these baseline values allowed us to draw up a predictive arithmetic score that could be used to predict radiologic damage at 3 years and radiologic progression in individual patients.     

Progression of radiographic joint erosion during low dose corticosteroid treatment of rheumatoid arthritis

OBJECTIVE: The reported prevention of joint damage during treatment with prednisolone 7.5 mg daily in patients with early rheumatoid arthritis (RA)3 may have important implications for management of RA. We evaluated this observation in another patient population. METHODS: Radiographic progression rates in paired hand radiographs were analyzed in 824 patients with RA who participated in a 3 year prospective, randomized clinical trial comparing the nonsteroidal antiinflammatory drugs (NSAID) etodolac (150 or 500 mg bid) and ibuprofen (600 mg qid). Disease modifying antirheumatic drugs (DMARD) were not permitted. Prednisone < or=5 mg daily was continued by 197 patients (mean dose 4.37 mg daily) who had started prednisone therapy at least 6 mo before study entry, but new prednisone starts were not allowed. Standardized hand/wrist radiographs were done yearly and at dropout; joint erosion and narrowing scores of 3 readers were averaged and progression rates were compared. RESULTS: Mean duration of RA was 3.6 years (range 1-7); patients' ages were 21-78 years; 71% were women. Among the 824 patients, those taking prednisone were more likely to have had previous DMARD, and at study entry had higher radiographic scores for joint erosion and joint space narrowing and slightly higher swollen joint counts, C-reactive protein values, and rheumatoid factor titers than those not taking prednisone. However, for the subgroup of 252 patients with RA duration of 12-24 months, prestudy radiographic scores were not different in those taking or not taking prednisone. The mean (+/-SD) monthly rate of increase in erosion scores was 0.228 +/-0.37 for the prednisone patients and 0.206+/-0.35 for patients not taking prednisone (p = 0.994 by ANCOVA). The subgroup with 12 to 24 months' disease duration at entry also showed no significant effect of prednisone treatment on erosion progression. CONCLUSION: Clinically indicated low dose prednisone did not prevent progressive radiographic damage in 197 NSAID treated patients whose physicians had initiated < or =5 mg daily before study entry. The risk/benefit ratio of chronic low dose prednisone in early RA remains uncertain.     

Patient retention and hand-wrist radiograph progression of rheumatoid arthritis during a 3-year prospective study that prohibited disease modifying antirheumatic drugs

OBJECTIVE: To quantitate patient retention and radiographic progression rates in serial hand/wrist radiographs of patients with rheumatoid arthritis (RA) who were not being treated with disease modifying antirheumatic drugs (DMARD). METHODS: A total of 1433 RA patients with 1-7 years' disease duration entered a 3-year prospective randomized double-blind clinical trial comparing the nonsteroidal antiinflammatory drugs (NSAID) etodolac (300 or 1000 mg daily) and ibuprofen (2400 mg daily). Standardized hand/wrist radiographs were obtained yearly and at dropout if > 6 months after entry. DMARD were not permitted. Joint erosion, joint space narrowing (JSN), and total scores of 3 readers were averaged. RESULTS: At entry, mean duration of RA was 3.5 years (range 1-7); ages were 21-78 years; patients were 71% female, 84% Caucasian, 67% rheumatoid factor (RF) positive; tender joint count was 29, swollen joint count 22, Westergren erythrocyte sedimentation rate (ESR) 49, and C-reactive protein (CRP) 2.44. There were 824 (57.5%) patients who completed >or= 6 months and had paired radiographs; 46% completed 48 weeks; 31%, 98 weeks; and 19%, 147 weeks. Months between paired radiographs (time in study) averaged 23.1 (range 6-36). Mean progression rates for total, erosion, and JSN scores (5.08, 2.53, and 2.54 units per year, respectively) were significantly associated with time in study, baseline RF, ESR, CRP, swollen joint count, presence of erosions at entry, and with 20% and 50% composite clinical responses. Painful joint count and RA duration were weakly associated only with progression of erosions. Progression rates were not associated with age, sex, corticosteroid use, or prior DMARD use. Patients who completed the 3-year trial had less severe disease activity and radiographic progression than those who dropped out. CONCLUSION: In this 3-year prospective double-blind clinical trial that prohibited DMARD, retention rates (57.5%, 46%, 31%, and 19% at 0.5, 1, 2, and 3 years) were similar to those in the non-DMARD-treated placebo groups of recent published studies. Radiographic progression rates are reported for 824 non-DMARD-treated patients during RA of 1-10 years' duration. This information may be useful as background information in the interpretation of longterm clinical trials that evaluate joint radiographic outcomes.     

Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis

OBJECTIVE: Calprotectin is a major leucocyte protein, shown to correlate well with laboratory and clinical assessments in several inflammatory rheumatic diseases, and large concentrations of calprotectin have been found in synovial fluid from patients with rheumatoid arthritis (RA). The objective of the present study was to examine correlations between calprotectin and joint damage. METHODS: 145 patients with RA were analysed cross sectionally with laboratory (calprotectin, C reactive protein (CRP), and erythrocyte sedimentation rate (ESR)), clinical (28 joint counts (tender, swollen), physician global VAS, DAS28 and RA Articular Damage score (RAAD)), and radiographic (plain hand radiographs; modified Sharp's method) measurements, on the same day. RESULTS: Calprotectin showed a highly significant correlation with measures of joint damage; modified Sharp score r = 0.43 (p<0.001) and RAAD r = 0.40 (p<0.001). The association with modified Sharp score and RAAD score was maintained after adjustment for CRP, ESR, rheumatoid factor, DAS28, sex, and age in a multiple regression analysis (p = 0.018 and p = 0.04, respectively), while neither CRP nor ESR showed any independent associations. Highly significant correlations (p<0.001) were also found between calprotectin and both laboratory and clinical markers of inflammation. CONCLUSION: Calprotectin was found to significantly and independently explain the variation in the radiological and clinical assessments of joint damage. Longitudinal studies are required to examine whether calprotectin may predict the progression of joint damage in RA.     

Classifying structural joint damage in rheumatoid arthritis as progressive or nonprogressive using a composite definition of joint radiographic change: a preliminary proposal

OBJECTIVE: To categorize radiographic joint damage as progressive or nonprogressive in individuals with rheumatoid arthritis (RA) participating in clinical studies. METHODS: Using the total Sharp radiographic damage score, erosion score, and joint space narrowing (JSN) score for 751 serial films of the hand/wrist and forefoot obtained from 190 patients with early RA during 6-60 months of followup (mean 31 months), various threshold values for progression of joint damage were evaluated singly and in various combinations. For each patient, the progression rate was estimated from the linear regression line for all available radiographic time points. After preliminary screening, 23 candidate definitions were tested to select a definition that discriminated well between radiographic progression and radiographic nonprogression. RESULTS: The definition selected describes radiographic nonprogression in individual patients as an increase of < or =0.1 in the standardized response mean of the trimmed population (the central 95% of patients) for > or =5 of 6 change measures (erosion scores and JSN scores for the fingers, wrists, and feet). Using this definition, 59% of the 190 patients with early RA were defined as having nonprogressive radiographic damage. Moreover, 95% of 95 patients with progression of the total Sharp score at or below the median and 24% of 95 patients with progression of the total Sharp score above the median were defined as having nonprogressive joint damage (chi(2) = 98, P < 0.0001), as were 97% of patients in the lowest quintile of total Sharp score progression rates and none of the patients in the highest progression quintile. Patients defined as nonprogressors had significantly lower baseline levels of C-reactive protein and lower erythrocyte sedimentation rates compared with patients defined as progressors, and those patients in the nonprogressive joint damage group more frequently had American College of Rheumatology 20% and 50% improvement criteria responses, "good" improvements (decrease of > or =1.2) in the Disease Activity Score, and > or =50% decreases in the swollen joint counts during the first 2 years of followup. CONCLUSION: RA joint damage in an observational cohort can be classified as progressive or nonprogressive with the use of a composite definition. Validation and/or refinement of this definition is needed by utilizing the data from controlled clinical trials that compare placebo with active treatment.     

Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: A meta-analysis

OBJECTIVE: Although early initiation of disease-modifying antirheumatic drugs (DMARDs) is effective in controlling short-term joint damage in individuals with rheumatoid arthritis (RA), the long-term benefit in disease progression is still controversial. We examined the long-term benefit of early DMARD initiation on radiographic progression in early RA. METHODS: We identified published and unpublished clinical trials and observational studies from 1966 to September 2004 examining the association between delay to treatment initiation and progressive radiographic joint damage. We included studies of persons with RA disease duration <2 years and DMARD therapy of similar efficacy during followup. The differences in annual rates of radiographic progression between early and delayed therapy were pooled as standardized mean differences (SMDs). RESULTS: A total of 12 studies met the inclusion criteria. The pooled estimate of effects from these studies demonstrated a significant reduction of radiographic progression in patients treated early (-0.19 SMD, 95% confidence interval [95% CI] -0.34, -0.04), which corresponded to a -33% reduction (95% CI -50, -16) in long-term progression rates compared with patients treated later. Patients with more aggressive disease seemed to benefit most from early DMARD initiation (P = 0.04). CONCLUSION: These results support the existence of a critical period to initiate antirheumatic therapy, a therapeutic window of opportunity early in the course of RA associated with sustained benefit in radiographic progression for up to 5 years. Prompt initiation of antirheumatic therapy in persons with RA may alter the long-term course of the disease.     

Scores for functional disability in patients with rheumatoid arthritis are correlated at higher levels with pain scores than with radiographic scores

OBJECTIVE: To analyze correlations of functional disability scores with other measures of clinical status, in particular, Larsen radiographic scores and pain scores, in patients with rheumatoid arthritis (RA). METHODS: The functional capacity of 141 patients with RA (102 women, 39 men; median age 57 years; median disease duration 11.8 years; 83% rheumatoid factor positive) was assessed according to the Stanford Health Assessment Questionnaire (HAQ). Other variables studied included Larsen scores for radiographic damage of the small joints of the hands, wrists, and feet, pain scores by visual analog scale (VAS), Disease Activity Scores, general health scores by VAS, and Beck Depression Inventory (BDI) scores. RESULTS: The Spearman correlation coefficient comparing HAQ and Larsen scores was 0.277 (P = 0.001) and between HAQ and pain scores 0.652 (P < 0.001). In regression analysis, pain scores explained 41.4% of the variation in HAQ scores, normalized Larsen scores explained 7.3%, and BDI scores explained 5.5%; other variables were not significant in the model. CONCLUSION: Functional capacity scores of patients with RA are correlated at higher levels with pain scores than with radiographic scores of small joints.     

Association of early radiographic damage with impaired physical function in rheumatoid arthritis: a ten-year, longitudinal observational study in 238 patients

OBJECTIVE: To investigate the longitudinal relationship between physical disability, disease activity, and radiographic damage over 10 years in patients with rheumatoid arthritis (RA). METHODS: A cohort of 238 consecutively enrolled RA patients from the European Research on Incapacitating Disease and Social Support study (age range 20-70 years, mean disease duration 2.3 years, 68% rheumatoid factor [RF] positive) was followed up longitudinally for 10 years. Assessments at baseline and at years 1, 2, 5, and 10 comprised review of demographic variables, measurement of disease activity with the erythrocyte sedimentation rate (ESR), functional evaluations using the Health Assessment Questionnaire (HAQ) and grip strength (average value of the right and left hand), and radiographs of the hands scored by the van der Heijde modification of the Sharp method. Marginal modeling by generalized estimating equations was used to study the longitudinal relationship between the ESR and modified Sharp radiographic damage score with respect to explaining the HAQ score and grip strength. Age, sex, RF status, and disease duration were entered as covariates. RESULTS: The HAQ score and grip strength were longitudinally associated with the momentary modified Sharp/van der Heijde score as well as with progression in this score, independent of the ESR. Therefore, an increase of 10 units in the modified Sharp/van der Heijde score will result in a 0.03-unit increase in HAQ score and a 0.95-kg decrease in grip strength, after adjustment for the ESR. CONCLUSION: This 10-year observational study provides evidence that both radiographic damage and disease activity are independent contributors to impaired physical function in RA, both early and late in the disease process.     

Rheumatoid factor measured by fluoroimmunoassay: a responsive measure of rheumatoid arthritis disease activity that is associated with joint damage

OBJECTIVES: To determine whether rheumatoid factors (RFs), measured as continuous variables by time resolved fluoroimmunoassay, reflect disease activity in rheumatoid arthritis (RA). Further, to study the association of RFs and other disease activity parameters with radiological joint damage, especially in individual patients. METHODS: In active, early RA, IgM and IgA RFs, as well as erythrocyte sedimentation rate (ESR), C reactive protein (CRP), tender joint score, and swollen joint score were assessed regularly. At the study start and at 56 and 80 weeks, radiographs of hands and feet were assessed by the Sharp score (van der Heijde modification). Associations between RFs and disease activity parameters were studied. In addition, associations between radiographic damage and disease activity parameters (baseline and time integrated) were analysed by non-parametric tests and multiple regression analysis. The relation between time integrated disease activity parameters and radiological damage in individual patients was analysed and visualised. RESULTS: 155 patients were included. RF levels were strongly associated with the disease activity parameters (especially ESR and CRP) and with each other. All disease activity parameters, at baseline as well as time integrated parameters, were associated with (the progression of) radiographic damage. Moreover, in individual patients, a linear relationship between time integrated disease activity parameters and progression of radiological damage was seen. CONCLUSION: RFs, measured as continuous variables, can be considered as disease activity parameters in patients with RA. The level of RF at baseline and the exposure to RF over time is associated with radiological damage. In individual patients, there is a constant relation between disease activity and radiological damage.