Predictors of remission,erosive disease and radiographic progression in a Colombian cohort of early onset rheumatoid arthritis: a 3-year follow-up study

The objective of the study is to find predictors of remission, radiographic progression (RP), and erosive disease in a cohort of patients with early onset rheumatoid arthritis (EORA) that followed a therapeutic protocol aiming at remission, in a real world tight-control setting. EORA patients were enrolled in a 3-year follow-up study. Clinical, biological, immunogenetic, and radiographical data were analyzed. Radiographs were scored according to Sharp–van der Heijde (SvdH) method. RP was defined by an increase of 3 units in 36 months. Remission was defined as DAS28 <2.6. A stepwise multiple logistic regression model was used to identify independent predictors of the three target outcomes. One hundred twenty-nine patients were included. Baseline disease activity was high. Significant overall improvement was observed, but only 33.3 % achieved remission. At 36 month, 50.4 % (65) of patients showed erosions. RP was observed in 62.7 % (81) of cases. Statistical analysis showed that baseline SvdH score was the only predictive factor associated with the three outcomes evaluated. Lower HAQ-DI and absence of autoantibodies were predictive of remission. Higher levels of ESR and presence of erosions at entry were predictive of RP. Independent baseline predictors of incident erosive disease were anti-CCP and RF positivity, symptom duration at baseline >3 months, and presence of HLA-DRB1 shared epitope. Radiographic damage at baseline was the main predictor of outcomes. Autoantibodies, HAQ and ESR at baseline, symptom duration before diagnosis, and HLA-DRB1 status had influence on clinical course and development of structural joint damage in Colombian RA patients.     

Does the serum level of IgA-alpha-1-antitrypsin complex correlate with radiological progression in early rheumatoid arthritis? A 3-year follow-up study

We followed the levels of serum IgA-alpha-1-antitrypsin (IgA-AT) complex in 37 patients with early rheumatoid arthritis (RA) during the first 3 years of the disease. The changes in IgA-AT were correlated with a radiological damage score (DS) of the hands assessed according to Larsen. At the onset of the disease, the IgA-AT serum concentration was significantly higher as compared to the control group (0.72±0.22 U vs 0.29±0.14 U, P<0.01). The level significantly decreased during the 3-year observation period. The DS was significantly higher after 3 years. However, this difference was due to changes in only 11 patients; in 26 patients the DS was almost unchanged. In the group of 11 patients with radiological progression, the level of IgA-AT either remained high or increased significantly (0.95±0.18 U at the onset, 0.97±0.25 U after 3 years), whereas we observed a decrease in IgA-AT in 26 patients without radiological progression (0.63±0.16 U at the onset of the disease, 0.45±0.10 U after 3 years, P<0.01). Moreover, a relationship between changes in IgA-AT serum level and radiological progression was shown (r=0.60, P<0.01). Our studies suggested that the relationship between IgA-AT level and radiological progression of the disease should be considered. We cannot exclude the possibility that the constant high level of IgA-AT may cause worsening in bone erosions.     

A 15-year follow-up study on the outcome in patients with early rheumatoid arthritis

This study aimed to investigate the natural course of early rheumatoid arthritis (RA) after treatment for 15 years based on the present data of patients who had been enrolled in a 1 year study of early RA conducted by the Japan Rheumatism Foundation in 1981 and 1982. An examination form was mailed to each doctor who had participated in the previous study requesting them to record the present data of the patients. The patients were requested to fill out the AIMS2 questionnaire. Patients had been randomly assigned into three treatment groups: those treated with gold, with d-penicillamine and without slow acting antirheumatic drugs (SAARDs). Information was obtained concerning 74 of 161 patients who had completed the previous 1 year study. Clinical remission was observed in 20 of 74 patients. The current status of RA by physician’s assessment was reported to be well controlled in 32 of 48 cases (66.7%); however, no remarkable improvement was seen in erythrocyte sedimentation rate (ESR, and the number of painful joints compared with the values at entry 15 years previously. Radiographical stages showed progression and the average score of AIMS2 had deteriorated in most cases. High ESR, progression of joint damage and positive rheumatoid factors at the early stage of RA were suggested to be factors relating to QOL deterioration. These results suggest that it would be difficult to modify the natural course of RA by currently used treatment strategies with SAARDs.     

A 15-year follow-up study on the outcome in patients with early rheumatoid arthritis

Abstract

This study aimed to investigate the natural course of early rheumatoid arthritis (RA) after treatment for 15 years based on the present data of patients who had been enrolled in a 1 year study of early RA conducted by the Japan Rheumatism Foundation in 1981 and 1982. An examination form was mailed to each doctor who had participated in the previous study requesting them to record the present data of the patients. The patients were requested to fill out the AIMS2 questionnaire. Patients had been randomly assigned into three treatment groups: those treated with gold, with d-penicillamine and without slow acting antirheumatic drugs (SAARDs). Information was obtained concerning 74 of 161 patients who had completed the previous 1 year study. Clinical remission was observed in 20 of 74 patients. The current status of RA by physician’s assessment was reported to be well controlled in 32 of 48 cases (66.7%); however, no remarkable improvement was seen in erythrocyte sedimentation rate (ESR, and the number of painful joints compared with the values at entry 15 years previously. Radiographical stages showed progression and the average score of AIMS2 had deteriorated in most cases. High ESR, progression of joint damage and positive rheumatoid factors at the early stage of RA were suggested to be factors relating to QOL deterioration. These results suggest that it would be difficult to modify the natural course of RA by currently used treatment strategies with SAARDs.     

Radiographic remission in seropositive rheumatoid arthritis. A 20-year follow-up study

OBJECTIVE: Rheumatoid arthritis (RA) is in most instances a progressive disease. Very little information is available on halting of the radiographic damage, particularly in later phases of the disease. We studied radiographic remission of RA lasting to the end of follow-up, covering the period 1973-96. METHODS: Radiographs of hands and feet were taken at onset and at 1, 3, 8, 15 and 20 years from entry in 102 cases of recent onset (< 6 months) seropositive and erosive RA. A Larsen score of 0-100 was formed for 20 joints of hands and feet. If the score did not worsen by more than one point between one of the above time points and the end of the study, the patient was considered to be in remission. RESULTS: Remission was confirmed in 27 (26%) of the patients. In 3 cases the remission was from the 1-year check-up, in 5 from the 3-year check-up, in 6 from the 8-year check-up and in 13 cases from the 15-year check-up. Some of the remission cases had a mild disease from the outset, but there were cases in which the disease process had led to marked joint destruction before slowing down. CONCLUSION: This data may serve as a basis for comparison with subsequent cohort studies on new treatments-of-choice.     

Need and sequence of large joint replacements in rheumatoid arthritis. A 25-year follow-up study

OBJECTIVE: The aim of the present study was to evaluate the number and sequence of large joint replacements (LJR) performed in long-term rheumatoid arthritis (RA) from an inception cohort of 103 patients with rheumatoid factor (RF)-positive RA followed over 25 years. METHODS: A total of 83 patients attended the 15-year and 68 patients the 20-year follow-up. Patient documents and radiographs were evaluated in the beginning of 2001 and a complementary interview was arranged to assess the number and sequence (timing) of LJRs performed. RESULTS: The cumulative number of LJRs performed for 22 patients (19 women) during the 25 years of follow-up was 41. Seventeen total hip joint replacements (THR) (42% of the total number of 41 LURs) were performed on 13 patients, median time from the diagnosis to the operation being 14 years; 14 total knee replacements (TKR) (34%) on 11 patients (after a median time of 17 years); 3 total shoulder replacements (TSR) (7%) on 3 patients (median time of 18 years); and 7 total elbow replacements (TER) (17%) on 4 patients (median time of 21 years), respectively. Six patients had undergone three or more LJRs during the follow-up period. CONCLUSION: During our 25 years of follow-up, in 27% of RA patients LUR was needed, and 41% of them needed more than one replacement.     

Low-cost, low-field dedicated extremity magnetic resonance imaging in early rheumatoid arthritis: a 1-year follow-up study

OBJECTIVE: To study the ability of low-cost low-field dedicated extremity magnetic resonance imaging (E-MRI) to assess and predict erosive joint damage in the wrist and metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis. METHODS: 24 previously untreated patients with rheumatoid arthritis with joint symptoms for <1 year were evaluated at the time of diagnosis and after 6 and 12 months of methotrexate treatment with conventional clinical or biochemical examinations, x rays of both hands and wrists, and E-MRI of the dominant wrist and MCP joints. RESULTS: At baseline, all patients showed magnetic resonance imaging (MRI) synovitis, and MRI erosions were detected in 21 bones (10 patients). 6 (29%) of these, distributed among two patients, were seen on x ray. One x ray erosion was not detected by MRI. At 1 year, MRI and x ray detected 15 and 8 new erosions, respectively, and 19% of MRI erosions at baseline had progressed to x ray erosions. In bones with MRI erosions at baseline, the relative risk of having x ray erosions at the 1-year follow-up was 12.1, compared with bones without baseline MRI erosions (lesion-centred analysis). If bones with baseline x ray erosions were excluded, the relative risk was 5.2. In patients with baseline MRI bone erosion or oedema, the relative risk of having x ray erosions at 1 year was 4.0, compared with patients without these signs at baseline (patient-centred analysis). CONCLUSION: In this group of patients with early rheumatoid arthritis who were treated uniformly, baseline E-MRI erosions in MCP or wrist bones markedly increased the risk of x ray erosions at the 1-year follow-up. Low-cost, low-field dedicated extremity MRI is promising for assessment and prognostication of early rheumatoid arthritis.     

Frequency of remissions in early rheumatoid arthritis defined by 3 sets of criteria. a 5-year followup study

OBJECTIVE: To study the frequency of remission using 3 sets of criteria in patients with rheumatoid arthritis (RA) at 5 years after the diagnosis. METHODS: All adult patients with recent onset inflammatory arthritis who did not meet criteria or show clinical signs of other specific arthritides were included in the RA1997 inception cohort at Jyv?skyl? Central Hospital, Finland, and were assessed for remission at 5-year control examination. Remission was defined as (1) American College of Rheumatology (ACR) remission (fatigue excluded), (2) clinical remission with no tender and no swollen joints and normal erythrocyte sedimentation rate, and (3) radiographic remission with no worsening of erosions and no new erosions from baseline to 5 years. RESULTS: The study included 127 patients with early RA (mean age 56 yrs, 61% female, 54% with positive rheumatoid factor, and 25% with erosions). At 5 years, 111 patients were examined, 17% (95% CI 11%-25%) of whom met ACR remission criteria, 37% (95% CI 28%-47%) met clinical remission criteria, and 55% (95% CI 49%-68%) met radiographic remission criteria. Only 13 (12%) patients met all 3 sets of remission criteria. The rate of remission was statistically significantly different (p < 0.001) using the 3 sets. CONCLUSION: The rate of remission in RA depends on the criteria used. No gold standard exists for defining remission in RA. A set of criteria including no sign of inflammatory activity and no radiographic progression might be a basis for development of clinically relevant remission criteria for RA.     

IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF detected by ELISA in rheumatoid arthritis.

One hundred patients with rheumatoid arthritis (RA), of whom 73 were seropositive by latex or Waaler-Rose (WR) assays, or both, 100 healthy subjects, and 102 diseased controls (22 patients with systemic lupus erythematosus (SLE) and 80 with bronchial asthma) were evaluated for the presence of IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF by an enzyme linked immunosorbent assay (ELISA). Ninety two per cent, 65%, 68%, and 66% of the patients with RA were found to be positive for IgM, IgA, IgE, and IgG respectively. A positive correlation existed between the levels of IgM RF and IgA RF on the one hand and disease activity on the other, and the levels of IgM RF and IgA RF correlated with the levels of circulating immune complexes as measured by a C1q binding assay. The presence of extra-articular features also correlated positively with the levels of IgA RF and IgE RF. Five out of six patients with Sjögren''s syndrome had very high levels of IgA RF. Of 47 patients typed for HLA-DR, DR1 and DR2 were significantly more frequent in those with the highest levels of IgM RF. Conversely, DR3 was associated with low levels or absence of IgA RF and IgE RF. These results suggest that immune response genes may regulate the level of different RF isotypes. The frequencies of IgM, IgA, IgE, and IgG RF were 59%, 36%, 9%, and 27% respectively in SLE and 25%, 2.5%, 70%, and 59% in bronchial asthma.     

Radiological progression in early rheumatoid arthritis after DMARDS: a one-year follow-up study in a clinical setting

OBJECTIVE: To analyse the frequency and prognostic factors of radiographic progression in a series of Spanish patients with early rheumatoid arthritis (RA) after 1 yr of treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Sixty patients (47 females, 13 males) with RA with a disease duration shorter than 2 yr [mean (s.d.) duration 9.5+/-6.6 months] were treated with the same therapeutic protocol using gold salts as the first DMARD and methotrexate as a second option, and were followed up for 1 yr. Radiographic progression in the hands and feet (total radiographic Larsen score and the erosion joint count) was used as the outcome variable. Clinical, laboratory, immunogenetic and radiographic data were obtained at study entry. Disease activity and response to therapy were measured at 6 and 12 months. RESULTS: Erosive disease was found in 21.7% of patients at baseline and in 38.3% after 1 yr. Although a substantial reduction in disease activity was observed during the 1 yr follow-up [disease activity score (DAS28) 5.8+/-0.8 at entry and 3.9+/-1.3 at 12 months, P < 0.001], the Larsen score rose from 1.9+/-3.3 to 5.6+/-9.8 after 1 yr. In 26.6% of patients, a raised erosion joint count was observed after 1 yr. Radiographic progression in the total joint radiographic damage (increase in Larsen score of >or=2) was observed in 36.6%. In the multivariate analysis, baseline pain [visual analogue scale (VAS)] and the presence of two copies of the shared epitope were associated with radiographic progression in the erosion joint count. Disease duration before study entry, VAS pain and Larsen score at baseline were significant predictors of radiographic progression in total damage (Larsen score). Baseline radiographic damage had the highest positive predictive value for progression. CONCLUSIONS: Radiographic progression was observed in up to 36.6% of patients with early RA after 1 yr of DMARD therapy in spite of a significant reduction in disease activity. Baseline factors, such as VAS pain, disease duration until DMARD therapy, damage score at baseline and the presence of two copies of the shared epitope, were associated with radiographic progression.     

Overt psychopathology in rheumatoid arthritis. A fifteen-year follow-up study

A 15-year follow-up study of 74 female patients (mean age 57.9 years) with definite or classic rheumatoid arthritis (RA) was performed, with special emphasis on overt psychopathology during the clinical course of the illness. Catamnestic investigation revealed that in 46% of the patients psychiatric disturbances necessitating treatment had appeared during the follow-up period. Generally, the psychiatric syndromes observed were of neurotic type not infrequently associated with depressive symptomatology. At the time of investigation 41% of the patients exhibited overt psychopathology, of whom the majority had depressive reactions (40%) or other forms of neurotic syndromes (18%). Only one patient was diagnosed as psychotic. In 5 instances distinct signs of chronic organic brain syndrome were noted. The importance of identifying clinical depression and of instituting adequate drug treatment and psychotherapy is emphasized.     

Serum matrix metalloproteinase 3 in early rheumatoid arthritis is correlated with disease activity and radiological progression

OBJECTIVE: To analyze the clinical significance of serial measurements of serum matrix metalloproteinase 3 (MMP-3) levels in relation to markers of disease activity and radiological progression in early rheumatoid arthritis (RA). METHODS: In a 3 year prospective study of 33 patients with early RA (symptoms < 1 year at entry) monthly measurements of serum MMP-3 were transformed into time integrated values for 6 month periods for comparison with other markers of disease activity like swollen joint count (SJC), tender joint count (TJC), Ritchie articular index (RAI), the disease activity score (DAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and radiological progression, scored according to Sharp's method, in which erosions and joint space narrowing are scored separately and combined to a total Sharp score. RESULTS: Significant correlations were found between serum MMP-3 and SJC, ESR, and CRP during all periods and between 6 and 30 months with the DAS. There were no correlations between serum MMP-3 and TJC or the RAI. During the first 12 months serum MMP-3 was correlated only with the item joint space narrowing of the Sharp score. After 12 months of followup it was also correlated with the total Sharp score and after 18 months it was correlated with all 3 items of the Sharp score. There was a wide interindividual variation in the relation between serum MMP-3 and radiological progression but intraindividually this relation seemed to be rather constant. CONCLUSION: Time integrated values of serum MMP-3 are correlated with time integrated values of other markers of disease activity such as joint swelling, ESR, CRP, and the DAS. Of the radiological scores, as outcome measures, especially joint space narrowing correlated closely with cumulative serum MMP-3.     

Antibodies to type II collagen in early rheumatoid arthritis. Correlation with disease progression

Objective. To establish that frequencies and levels of IgG antibodies to type II collagen are higher in early rheumatoid arthritis (RA), and to correlate these results with disease activity. Methods. Forty-four patients were characterized as having early RA. Patient sera obtained at initial presentation and at 12 months were tested by enzyme-linked immunosorbent assay for IgG antibodies to native and denatured type II collagen. Results. IgG antibodies to native and denatured type II collagen were detected at initial presentation in 27% and 82% of patients, respectively, and after 12 months in 14% and 50%, respectively. The presence of antibodies to native collagen was associated with activity of RA and severity of symptoms, and loss of antibodies at 12 months was associated with initially erosive RA and the DRB1 disease susceptibility motif. Conclusion. Levels of serum IgG antibodies to collagen in RA decrease over time and, therefore, are not attributable simply to cartilage destruction. The presence of early positivity for these antibodies, together with the RA susceptibility motif, appears to be predictive of rapidly progressive RA.     

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.     

Cytokines, metalloproteinases, their inhibitors and cartilage oligomeric matrix protein: relationship to radiological progression and inflammation in early rheumatoid arthritis. A prospective 5-year study

OBJECTIVE: To assess how serum concentrations of some cytokines, proteases and their inhibitors and cartilage oligomeric matrix protein (COMP) relate to the evolution of clinical disease and joint damage in early rheumatoid arthritis (RA). METHODS: Annual assessment was performed in 24 RA patients subdivided into three groups according to disease severity as determined by the radiological progression rate. All patients were followed for 5 yr after inclusion. Functional status, Larsen's radiographic index in hands and feet (joint damage score, JDS) and C-reactive protein (CRP) were assessed annually and compared with interleukin (IL)-6, IL-10, the IL-1 receptor antagonist (IL-1Ra), promatrix metalloproteinase 3 (proMMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1) and COMP, which were determined by specific immunological tests. RESULTS: The median JDS was initially between 4.5 and 7. During the study time the progression of JDS was 1 (median) for patients with slow progression, 33 for patients with intermediate progression and 62 for patients with rapid progression. Changes in CRP and proMMP-3 concentrations over time differed significantly between the groups, but no significant difference was observed for IL-1Ra, TIMP-1 or COMP. ProMMP-3 was closely related to CRP at each time point. IL-6 correlated significantly with CRP at the last four annual follow-up examinations. CRP and proMMP-3 correlated with JDS at the last two or three examinations and the combined levels of these markers over 5 yr correlated significantly with joint damage progression (Spearman rank correlation 0.73 and 0.74 respectively). IL-1Ra showed a weak negative correlation with JDS, and COMP tended to correlate with JDS only at the start. The initial proMMP-3 concentration was the only significant variable predicting rapidly developing joint damage, but the predictive value was low. CONCLUSIONS: ProMMP-3 correlated closely at all time points with CRP, but gave little or no additional clinical information regarding inflammation or radiographic progression. IL-1Ra and TIMP-1 showed weaker, acute-phase-like variation, which may reflect pathogenic agonist/inhibitor imbalance in the evolution of RA. COMP, in contrast, did not reflect the inflammatory CRP-related component of the disease or the destructive aspect in this study.