Anticitrullinated protein/peptide antibody and its role in the diagnosis and prognosis of early rheumatoid arthritis.
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Arthritis, Rheumatoid↗
Biomedical subjects
J M Hazes
Publications and source records attributed to J M Hazes.
Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies.
PURPOSE: To compare the effect of delayed and early treatment strategies on disease outcome in patients with rheumatoid arthritis. SUBJECTS AND METHODS: Between 1993 and 1995, 109 patients diagnosed with probable or definite rheumatoid arthritis of recent onset were initially treated with analgesics; if they had persistent active disease, they were treated subsequently with the disease-modifying drugs chloroquine or salazopyrine (delayed treatment). Between 1996 and 1998, similar patients (n = 97) were promptly treated with either chloroquine or salazopyrine (early treatment). RESULTS: The median lag to the initiation of disease-modifying treatment was 15 days in the early treatment group and 123 days in the delayed treatment group. There was less radiologic joint damage after 2 years in the early treatment group (median Sharp score, 3.5; 95% confidence interval [CI]: 1 to 7) compared with the delayed treatment group (median Sharp score, 10; 95% CI: 5 to 15; P <0.05). The median area under the curve of the 2-year disease activity score was lower in the early treatment group (64 units; 95% CI: 59 to 69 units) compared with the delayed treatment group (73 units; 95% CI: 69 to 77 units; P = 0.002). CONCLUSION: In this nonrandomized comparison, early introduction of disease-modifying antirheumatic drugs was associated with a better disease outcome after 2 years.
Activities of Daily Living↗
Human leukocyte antigen-DQ and DR polymorphisms predict rheumatoid arthritis outcome better than DR alone.
Conflicting data have been published on the value of the shared epitope (SE) hypothesis in predicting disease outcome in rheumatoid arthritis (RA). Recently we have proposed an alternative hypothesis, referred to as the RA protection (RAP) model. In this model, the HLA-DQ loci carry predisposition while HLA-DRB1 alleles encoding the motif DERAA provide protection against severe RA. In the present study, we have compared the respective values of the models in predicting both remission and erosions in early RA patients. We made use of an early arthritis clinic in which 158 RA patients and 138 patients with undifferentiated arthritis were enrolled. Patients were typed for HLA-DQ and -DR using high resolution DNA typing methods. Homozygosity for predisposing HLA-DQ alleles was associated with no remission and high erosion score. The presence of DERAA-bearing DRB1 alleles was negatively associated with erosions in otherwise predisposed individuals and increased the chance of being in remission. We found that the RAP model was significantly better than the SE model in predicting remission rate and erosion scores at one and two years in early RA patients. We conclude that HLA polymorphism does not only affect RA susceptibility, but also protects against severe disease at early stage.
Alleles↗
The validity of the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire.
OBJECTIVE: To examine further the usefulness of a 30-item disease-specific quality of life (QoL) questionnaire in patients with rheumatoid arthritis (RA). METHODS: The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire was applied to two groups consisting of 210 and 300 patients with RA, one group with increasing difficulty in performing activities of daily living and one group with stable disease. The associations between the RAQoL and measures of utility, QoL, functional status and disease activity were evaluated. Factor analysis was carried out to investigate if one or more QoL dimensions could be distinguished within this questionnaire. RESULTS: Similar results regarding the association between the RAQoL and different sets of outcome measures were found in the two groups of patients. Regression analysis showed that about 75% of the variance of the RAQoL could be explained with variables of QoL, functional status and disease activity. Physical contact could be distinguished as a separate dimension within the RAQoL, in addition to the dimensions mobility/energy, self-care and mood/emotion. CONCLUSION: The RAQoL is a valid instrument for measuring QoL in different populations of patients with RA. Physical contact, a dimension that is not covered by other common instruments in RA, could be distinguished as a separate dimension within the questionnaire.
Adult↗
Evidence for a protective role of the human leukocyte antigen class II region in early rheumatoid arthritis.
OBJECTIVE: To analyse the distribution of predisposing DQ3 (DQB1*03(*04)/DQA1*03) and DQ5 (DQB1*0501/DQA1*01), shared epitope encoding and protective DRB1 alleles in patients with early rheumatoid arthritis (RA) and undifferentiated arthritis (UA). METHODS: Consecutive patients enrolled in an early arthritis clinic were DNA-typed for HLA-DQ and DR. RA patients (n=195), UA patients (n=160) and controls from the same region (n=306) were sorted according to their DQ-DR phenotypes: DQ3 vs DQ5 and the presence or absence of a protective DERAA-positive DRB1 molecule. The three groups were also sorted according to the shared epitope (SE) hypothesis. RESULTS: We observed the association of both DQ3 and DQ5 with RA. DQ3/3 homozygous individuals had the highest risk of developing disease [odds ratio (OR)=20.00]. Conversely DQ5, but not DQ3, was associated with undifferentiated arthritis (OR=2.15 vs 1.25). Consistent with these differences, DQ3-positive individuals had significantly more active disease at the first visit at the outpatient clinic than DQ5-positive patients. DRB1 alleles encoding a DERAA motif in their third hypervariable region provided a strong dominant protection against RA among DQ5-positive individuals and decreased arthritis activity among DQ3-positive patients. Individuals with SE-positive DR1, DR4 and DR10 alleles were also predisposed to RA, DR4/4 homozygous individuals having the highest risk of developing RA (OR=11.00). CONCLUSION: The DQ3-DR4/9 haplotypes are associated with RA. The DQ5-DR1/10 haplotypes are associated with less active disease, i.e. UA, and DERAA encoding DRB1 alleles modulate either predisposition to or the severity of RA. We propose that HLA polymorphism influences not only the initiation or perpetuation of RA but also protection against the disease.
Arthritis, Rheumatoid↗
The value of a continuous ambulatory activity monitor to quantify the amount and intensity of daily activity in patients with rheumatoid arthritis.
OBJECTIVE: To examine the reliability, validity, and responsiveness of a continuous ambulatory activity monitor in patients with rheumatoid arthritis (RA). METHODS: Forty-one patients with RA, participating in a randomized controlled trial examining the effect of an intensive exercise program, were assessed by means of the Dynaport ADL (activities of daily living) monitor (AM). The time spent on activities (locomotion, standing, and active sitting) during 24 hours and the intensity of trunk movement during these activities were recorded. To determine test-retest reliability 20 patients were reassessed with the AM one week after the first assessment. Construct validity of the AM was determined by comparing the AM results with physical fitness measures (muscle strength, endurance, joint mobility), disease activity, and functional status. As well, 37 patients were assessed 18 months after the first assessment to determine responsiveness. RESULTS: All AM measurements showed satisfactory test-retest reliability (ICC 0.63-0.76). AM measures were significantly associated with physical fitness, functional status, and disease activity, indicating construct validity of the AM. The AM could discriminate between patients with improvement and deterioration in physical fitness, indicating sufficient responsiveness of AM variables. CONCLUSION: This study shows the value of an ambulatory activity monitor to quantify both the amount and intensity of physical activity of patients with RA during a day in their own environment. The ambulatory activity monitor seems to be a promising instrument for research into rehabilitation of patients with RA.
Activities of Daily Living↗
Delayed referral of female patients with rheumatoid arthritis.
OBJECTIVE: To analyze whether sex differences in referral exist in patients with rheumatoid arthritis (RA). METHODS: At the Department of Rheumatology of the Leiden University Medical Center, a special early arthritis clinic (EAC) was established. General practitioners (GPs) were encouraged to refer patients with joint complaints to the EAC. Subsequently, the diagnosis RA was made by a rheumatologist. RESULTS: In this report, 142 women and 82 men were included. The delays in patient's first encounter with a GP for both sexes were comparable. However, a significant difference in the GP's delay in referring female patients with RA to the EAC in comparison with male patients was observed (median of 93 days vs 58 days; p = 0.008). CONCLUSION: This report determined GP referral delay of female patients to a rheumatologist. GPs should be made aware that early detection and early referral of patients with RA are crucial for early treatment.
Academic Medical Centers↗
Comparative responsiveness of four elbow scoring instruments in patients with rheumatoid arthritis.
OBJECTIVE: This prospective study investigated the comparative responsiveness to change of 4 different elbow scoring instruments: 2 Hospital for Special Surgery elbow assessment scales, the Mayo Clinic Elbow Performance Index, and the Elbow Functional Assessment (EFA) Scale. METHODS: A group of patients with rheumatoid arthritis (RA) (median age 60 yrs) undergoing either elbow arthroplasty (22 elbows) or synovectomy with radial head excision (3 elbows) were evaluated both before and after surgery (median 7 mo postoperatively). Changes in the scores obtained using the scales under study were calculated and analyzed. The patient's opinion of global perceived effect of the intervention was used as an external criterion to classify them as "improved" or "non-changed." Responsiveness was evaluated with 3 different statistical approaches: using paired t statistics (pre and postsurgery scores), effect size statistics (standardized response mean, effect size, and responsiveness ratios), and receiver operator characteristic curves. Minimal clinically important difference was estimated using patient satisfaction as the external criterion. RESULTS: Each of the elbow rating measures under study proved to be responsive to change when evaluating patients with RA undergoing elbow arthroplasty or synovectomy. The EFA scale had the highest power to detect a clinically meaningful difference and had the best discriminative ability to distinguish improved from no-change patients, as shown by all responsiveness statistics applied. CONCLUSION: Using the EFA scale requires smaller sample sizes to achieve a fixed level of statistical power than the other scales we studied.
Adult↗
Diagnostic strategies for the histological examination of muscle biopsy specimens for the assessment of vasculitis in rheumatoid arthritis.
For the diagnosis of rheumatoid vasculitis (RV), histological examination of a blindly-taken muscle biopsy is advocated. If fibrinoid necrosis (FN) is observed in one or more tissue sections of the biopsy the diagnosis of RV is confirmed. The diagnostic value of such histological investigation depends on the prevalence of FN in biopsies of RV patients, the number of tissue sections that are investigated, and the sampling design with which the tissue sections are obtained from the biopsy. In this paper we determine the mathematical relation between the sensitivity of the RV diagnosis and these three factors for four different models for the FN distribution in RV biopsies. The goodness-of-fit of these models was assessed by analysing 18 829 tissue sections of the biopsies of 56 patients, among which were 24 (otherwise histologically proven) RV patients. It appeared that the sensitivity was moderate: FN was observed in only 14 out of 24 (58 per cent) muscle biopsies of the RV patients. The prevalence of FN in the tissue sections of those 14 biopsies was low, about 17 per cent according to the best fitting model. We proved that the sampling design, maximizing the minimum distance between tissue sections (equidistant sampling) was optimal, and that with such optimal sampling, examination of about 20 tissue sections was sufficient. With practical sampling designs, however, considerably more tissue sections had to be inspected. FN appeared to cluster in the RV biopsies, and a first-order Markov model satisfactorily described the (auto)correlation between adjacent tissue sections in RV biopsies.
Arthritis, Rheumatoid↗
Dynamic exercise therapy for rheumatoid arthritis.
OBJECTIVES: To assess the effects of dynamic exercise therapy in improving joint mobility, muscle strength, aerobic capacity and daily functioning in patients with rheumatoid arthritis (RA). In addition, possible unwanted effects such as an increase in pain, disease activity and radiological progression were studied. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal trials register, the Cochrane Controlled trials Register, Medline, Embase and SCISEARCH databases up to may 1997 in order to controlled trials on the effect of exercise therapy. SELECTION CRITERIA: Randomized trials on the effect of dynamic exercise therapy in RA patients with an exercise program fulfilling the following criteria: a) intensity level such that heart rates exceeded 60% of maximal heart rate during at least 20 minutes, b) exercise frequency of two session per week, and c) duration of intervention of greater than six weeks DATA COLLECTION AND ANALYSIS: Two blinded reviewers independently selected eligible studies, rated the methodological quality and extracted data. MAIN RESULTS: Six out of 30 identified controlled trials met the inclusion criteria. Four of the six included studies fulfilled at least seven out of 10 methodological criteria. Due to heterogeneity in outcome measures, data could not be pooled. The results suggest that dynamic exercise therapy is effective at increasing aerobic capacity and muscle strength. No detrimental effects on disease activity and pain were observed. The effects of dynamic exercise therapy on functional ability and radiological progression are unclear. REVIEWER'S CONCLUSIONS: Dynamic exercise therapy has a positive effect on physical capacity. Research on the long-term effect of dynamic exercise therapy on radiological progression and functional ability is needed.
Arthritis, Rheumatoid↗
The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide.
OBJECTIVE: Since modern treatment of rheumatoid arthritis (RA) is shifting toward aggressive antirheumatic therapy in an early phase of the disease, diagnostic tests with high specificity are desirable. A new serologic test (anti-cyclic citrullinated peptide [anti-CCP] enzyme-linked immunosorbent assay [ELISA]) was developed to determine the presence of antibodies directed toward citrullinated peptides, using a synthetic peptide designed for this purpose. METHODS: A cyclic peptide variant that contains deiminated arginine (citrulline) was designed and used as antigenic substrate in ELISA. Test parameters and diagnostic characteristics of the test were studied in patients with and without RA, in patients with various infectious diseases, and in a group of patients from an early arthritis clinic (EAC). RESULTS: Using prevalent RA and non-RA sera, the anti-CCP ELISA proved to be extremely specific (98%), with a reasonable sensitivity (68%). Also, in the EAC study group, the anti-CCP ELISA appeared to be highly specific for RA (96%). In comparison with the IgM rheumatoid factor (IgM-RF) ELISA, the anti-CCP ELISA had a significantly higher specificity (96% for CCP versus 91% for IgM-RF; P = 0.016) at optimal cut-off values. The sensitivity of both tests for RA was moderate: 48% and 54% for the anti-CCP ELISA and the IgM-RF ELISA, respectively (P = 0.36). Combination of the anti-CCP and the IgM-RF ELISAs resulted in a significantly higher positive predictive value of 91% (P = 0.013) and a slightly lower negative predictive value of 78% (P = 0.35) as compared with the use of the IgM-RF ELISA alone. The ability of the 2 tests performed at the first visit to predict erosive disease at 2 years of followup in RA patients was comparable (positive predictive value 91%). CONCLUSION: The anti-CCP ELISA might be very useful for diagnostic and therapeutic strategies in RA of recent onset.
Adolescent↗
A comparison of three radiologic scoring systems for the long-term assessment of rheumatoid arthritis: findings of an ongoing prospective inception cohort study of 132 women followed up for a median of twelve years.
OBJECTIVE: To compare the sensitivity and efficiency of 3 different radiologic scoring systems in measuring radiologic progression of rheumatoid arthritis (RA) over a 12-year period. METHODS: Radiographs of the hands and feet of 112 RA patients were assessed at 0, 3, 6, and 12 years of disease duration using the Sharp score as modified by van der Heijde (SHS), the Sharp score with increased maximum scores (Sharp Max), and the Kellgren score. The sensitivity to change was tested using the standardized response mean (SRM); the efficiency was determined by calculating the number of patients needed to detect 50% difference in progression between 2 patient groups. RESULTS: Radiologic abnormalities were steadily progressive irrespective of the scoring method used. In early disease, the SRM was significantly larger for the SHS and Kellgren scores compared with the Sharp Max score. In late disease, the Kellgren score was slightly more sensitive to change compared with the SHS and Sharp Max scores; the difference, however, did not reach significance. In erosive disease, the SRM was significantly larger for the Kellgren compared with the SHS and Sharp Max scores. The numbers of patients needed to detect a 50% difference during the 0-3-year followup period were 129, 138, and 124 for the SHS, the Sharp Max, and the Kellgren, respectively. The numbers of patients needed to detect a 50% difference during the 6-12-year followup period were 117, 121, and 104, respectively. The numbers of patients needed to detect a 50% difference during the 6-12-year followup in patients with erosive disease were 74, 78, and 68, respectively, for the 3 scores. The Kellgren required 33 minutes to score 10 sets of radiographs of the hands and feet; the SHS score took 55 minutes. CONCLUSION: The Kellgren scoring system is the most efficient method for monitoring the radiologic progression of RA. The Kellgren and the SHS are equally sensitive to change early in the disease, whereas the Kellgren score becomes more sensitive to change late in the disease in patients with erosions.
Adult↗
The diagnostic value of streptococcal serology in early arthritis: a prospective cohort study.
OBJECTIVE: To evaluate the diagnostic value of streptococcal serology in adult early arthritis patients in discriminating between post-streptococcal reactive arthritis (PSRA) and arthritis with other causes. METHODS: The antistreptolysin-O (ASO) and anti-DNase B tests were performed at baseline in 366 consecutive, newly referred early arthritis patients. After 1 yr of follow-up the patients were classified according to international classification criteria and were evaluated for the presence of persistent arthritis. The outcome measures were the predictive value of streptococcal serology for the diagnosis of PSRA and the ability of this serology to discriminate at the first visit between the self-limiting and persistent forms of arthritis. RESULTS: With a positive serological result, the probability of having PSRA increased from 2 to 9%, whereas the probabilities of having rheumatoid arthritis or undifferentiated arthritis continued to be high (23 and 29%). The serological tests did not discriminate between the self-limiting and persistent forms of arthritis. The major Jones criteria apart from arthritis were not observed. CONCLUSION: Streptococcal serology has no diagnostic value in adult early arthritis patients in whom major Jones criteria other than arthritis are not present.
Adult↗
Radiographic damage of large joints in long-term rheumatoid arthritis and its relation to function.
OBJECTIVE: To describe the extent of radiographic damage of large joints in long-term rheumatoid arthritis (RA) and its relationship to small joint involvement and physical function. METHODS: After 12 yr of follow-up, radiographs of all large joints (Larsen large joint score 0-60) of 105 recent RA patients were assessed. Correlations were evaluated between the Larsen large joint score and radiographic damage of the hands and feet as measured by the van der Heijde modification of the Sharp score (SHS) and the health assessment questionnaire (HAQ). We determined the relative contributions of radiographic damage of small and large joints, disease activity and psychological function to the HAQ. RESULTS: The median Larsen large joint score was 3. In 54% of the patients at least one large joint was erosive. The correlation of the Larsen score with the SHS and HAQ scores was 0.76 and 0.60, respectively. Disease activity and radiographic damage of the large joints were the major determinants of the HAQ score. CONCLUSION: Large joint involvement after 12 yr of follow-up is extensive and is associated with functional disability. Large joint involvement is closely associated with small joint involvement.
Adult↗
Value of the time trade off method for measuring utilities in patients with rheumatoid arthritis.
OBJECTIVE: To assess the feasibility, reliability, and validity of the time trade off (TTO) in patients with rheumatoid arthritis (RA). METHODS: The TTO was applied in 194 patients with RA with increasing difficulty in performing activities of daily living. The test-retest reliability was determined in 35 of these patients and was calculated by the intraclass correlation coefficient (ICC). Construct validity was evaluated with the following sets of variables: measures of utility (rating scale), quality of life (RAND 36 item Health Status Survey (RAND-36) and RAQoL), functional status (Health Assessment Questionnaire, grip strength, and walk test), and disease activity (doctor's global assessment, disease activity score, pain, and morning stiffness). RESULTS: Ten patients (5%) did not complete the TTO. The median value of the TTO was 0.77 (range 0.03-1. 0). The test-retest ICC of the TTO was 0.85 (p<0.001). Construct validity testing of the TTO showed poor to moderate correlations (Spearman's r(s) between 0.19 and 0.36, p<0.01) with all outcome measures except for the subscale role limitation (physical problem) of the RAND-36, the walk test, the doctor's global assessment of disease activity, and morning stiffness. Multiple regression analysis showed that only 17% of the variance of the TTO scores could be explained. CONCLUSIONS: The TTO method appeared to be feasible and reliable in patients with RA. The poor to moderate correlations of the TTO with measures of quality of life, functional ability, and disease activity suggest that the TTO considers additional attributes of health status. This may have implications for the application of the TTO in clinical trials in patients with RA.
Activities of Daily Living↗
Effect of intensive exercise on patients with active rheumatoid arthritis: a randomised clinical trial.
OBJECTIVE: To investigate the effects of a dynamic, intensive exercise regimen on pain, disease activity, and physical functioning in active rheumatoid arthritis (RA). METHODS: 64 patients with RA with a mean age of 60 (13) years and mean disease duration of 8 (8) years, admitted to hospital because of active disease, were randomly assigned to an intensive exercise programme or to a conservative exercise programme during their period in hospital with a mean length of 30 (14) days. The intensive exercise programme consisted of knee and shoulder dynamic and isometric muscle strengthening exercises against resistance five times a week and conditioning bicycle training three times a week and was supplemental to the conservative exercise programme of range of motion and isometric exercises. Indices of disease activity, pain, muscle strength, and functional ability were assessed at 0, 3, 6, 12, and 24 weeks by a blinded observer. RESULTS: The medical treatment during the study was the same in both groups. Both groups improved in measures of disease activity, differences between groups were not statistically significant. The mean improvement in disease activity score at 24 weeks in the intensive and conservative exercise group was -1.4 (1. 5) and -0.7 (1.4), respectively. Measures of physical functioning improved significantly for patients in the intensive exercise group, and differences between groups were statistically significant for measures of muscle strength. CONCLUSION: A short term intensive exercise programme in active RA is more effective in improving muscle strength than a conservative exercise programme and does not have deleterious effects on disease activity.
Adult↗
The bone and joint decade 2000-2010.
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Bone Diseases↗
Long-term course and outcome of functional capacity in rheumatoid arthritis: the effect of disease activity and radiologic damage over time.
OBJECTIVE: To investigate the evolution of functional capacity, disease activity, and joint destruction over time in a 12-year prospective cohort of rheumatoid arthritis (RA) patients, and to study the relative contribution of disease activity and joint destruction to the loss of functional capacity. METHODS: One hundred thirty-two female patients with recent-onset RA were assessed at 0, 3, 6, and 12 years of followup for functional capacity (Health Assessment Questionnaire [HAQ] score), disease activity (Disease Activity Score [DAS]), and joint destruction (Sharp score of radiologic damage). RESULTS: The Sharp score deteriorated steadily over time, while the HAQ score and DAS showed a variable course. The DAS correlated strongly with the HAQ score throughout the disease course. The correlation between the Sharp score and the HAQ score was weak at study start, but became strong after 12 years. After 12 years of followup, disease activity was the main determinant of the HAQ score when entered in a multivariate analysis. CONCLUSION: Functional capacity is strongly influenced by disease activity throughout the course of RA. Even in longstanding RA, disease activity proves to be the main determinant of the HAQ score for functional capacity.
Adult↗