A. H. Zwinderman

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.

Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis

Objectives: To compare the occurrence of drug-free remission, functional ability and radiological damage after 4 years of response-driven treatment according to four different treatment strategies for rheumatoid arthritis (RA). Methods: Patients with recent-onset, active RA (n  =  508) were randomly assigned to four different treatment strategies: (1) sequential monotherapy; (2) step-up combination therapy; (3) initial combination therapy with prednisone and (4) initial combination therapy with infliximab. Treatment was adjusted based on 3-monthly disease activity score (DAS) assessments, aiming at a DAS ⩽2.4. From the third year, patients with a sustained DAS <1.6 discontinued treatment. Results: In total, 43% of patients were in remission (DAS <1.6) at 4 years and 13% were in drug-free remission: 14%, 12%, 8% and 18% of patients in groups 1–4, respectively. The absence of anti-cyclic citrullinated peptide antibodies, male gender and short symptom duration were independently associated with drug-free remission. Functional ability and remission were maintained in all four groups with the continuation of DAS-driven treatment, without significant differences between the groups. Significant progression of joint damage was observed in 38% and 31% of patients in groups 3 and 4 versus 51% and 54% of patients in groups 1 and 2 (p<0.05, group 4 versus groups 1 and 2, group 3 versus group 2). Conclusions: In patients with recent-onset active RA, drug-free remission was achieved in up to 18% of patients. DAS-driven treatment maintained clinical and functional improvement, independent of the treatment strategy. Joint damage progression remained significantly lower after initial combination therapy compared with initial monotherapy.

Clinical significance of rheumatoid factors in early rheumatoid arthritis: results of a follow up study.

Serum rheumatoid factors (RF) were measured yearly in 135 women with rheumatoid arthritis by the Waaler-Rose and latex fixation tests and IgM, IgA, and IgG RF were measured by enzyme linked immunosorbent assays (ELISAs). The patients were followed up from an early phase of the disease for a mean duration of six years. Patients with a persistently positive RF test, irrespective of the type of test used, had more radiological abnormalities, more disease activity, worse functional ability, more extra-articular manifestations, and needed more treatment with second line drugs than patients with persistently negative or variably positive and negative test results during the follow up. Increased RF levels, especially a high level of IgA RF within three years of the onset of symptoms, was prognostic for a more severe disease outcome six years after the onset of symptoms.

Factors associated with the development of vasculitis in rheumatoid arthritis: results of a case-control study.

OBJECTIVE: To investigate those characteristics of patients with rheumatoid arthritis (RA) that are associated with the development of rheumatoid vasculitis (RV). METHODS: Demographic and clinical data of 69 patients who had been diagnosed as having RV were compared with those of 138 contemporaneous control patients with RA who were not suspected to have vasculitis. Vasculitis was confirmed histologically in 96% of the subjects with RV. RESULTS: Variables associated with the development of RV were: 1) male gender, presence of increased serum concentrations of rheumatoid factor, joint erosions, subcutaneous nodules, number of disease modifying antirheumatic drugs previously prescribed, treatment (ever) with D-penicillamine or azathioprine; 2) presence of nail fold lesions and any other extrarticular feature one year before the time of diagnosis of RV; 3) treatment with corticosteroids at the time of diagnosis of RV. CONCLUSIONS: The development of RV is associated with male gender, extra-articular features, and a severe course of RA as indicated by the presence of joint destruction and need for intensive treatment with antirheumatic drugs. The strongest association was found with the presence of increased concentrations of rheumatoid factor.

Evidence of central nervous system damage in patients with neuropsychiatric systemic lupus erythematosus, demonstrated by magnetization transfer imaging

OBJECTIVE The clinical symptoms of neuropsychiatric systemic lupus erythematosus (NPSLE) are usually reversible, but whether the associated brain damage is also reversible is still a matter of debate. Since magnetization transfer imaging (MTI) is more sensitive than conventional magnetic resonance imaging (MRI) in demonstrating brain damage, it has become a useful tool in the detection and quantification of diffuse brain disorders such as multiple sclerosis. In this study, MTI was applied to investigate whether central nervous system (CNS) damage is present in patients with a history of NPSLE. METHODS Eleven female patients with a history of NPSLE and no previous or concurrent primary neurologic or psychiatric disease (ages 17-49 years), 11 female patients with SLE without a history of NPSLE (non-NPSLE; ages 15-51 years), and 10 healthy female controls (ages 17-47 years) underwent MTI. From these MTI scans, quantitative data on the uniformity of the brain parenchyma and atrophy were derived. RESULTS One NPSLE and 1 non-NPSLE patient were excluded from this study due to infarctions detected with conventional MRI. MTI measures normalized for intracranial volume, reflecting abnormalities of the brain parenchyma as well as atrophy, were lower (P < 0.001) in the NPSLE group than in both control groups. A higher (P < 0.005) mean ratio of cerebrospinal fluid to intracranial volume, indicative of atrophy, was present in the NPSLE group compared with either the non-NPSLE patients or healthy controls. Still, the MTI measures solely reflecting uniformity of the brain parenchyma (normalized for brain volume) were also significantly (P < 0.001) lower in the NPSLE patients than in both control groups. CONCLUSION This study demonstrates that using MTI, CNS damage can be demonstrated in patients with a history of NPSLE. MTI might, therefore, be an alternative and sensitive tool to detect brain injury in NPSLE, and might also be useful in studying the natural history of the disease.

Association of the TNF +489 polymorphism with susceptibility and radiographic damage in rheumatoid arthritis

Multiple genetic factors contribute to susceptibility to rheumatoid arthritis (RA). The extent of variability in disease presentation in RA may be related to genetic heterogeneity. In this study we investigated the association of the TNF gene polymorphism at position +489 with susceptibility to and severity of RA. Analysis of the frequency of the +489 A and G alleles in a group of 293 consecutive RA patients and 138 healthy controls revealed a significant decrease of the A allele. The +489 GA patients had a 3.9 times decreased chance of having erosive disease than +489 GG patients. These results were confirmed in a prospective study using a cohort of 112 patients who were followed for 12 years. The progression rate of the erosion score over 12 years expressed as Sharp score for X-rays of hands and feet was 3.4 per year for the GA-genotyped patients and 12.1 for the GG-genotyped patients. These associations were independent of rheumatoid factor and HLA-shared epitope positivity. In conclusion, these data suggest that the intron TNF +489 polymorphism is associated with susceptibility to and disease severity of RA independently of HLA-shared epitope-positive alleles.

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 (doctors 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 (Spearmans r sbetween 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 doctors 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.

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.