Objective. During the last decade, rheumatologists have learned to initiate disease-modifying antirheumatic drugs (DMARDs) early to improve the outcome of rheumatoid arthritis (RA). However, the... Show moreObjective. During the last decade, rheumatologists have learned to initiate disease-modifying antirheumatic drugs (DMARDs) early to improve the outcome of rheumatoid arthritis (RA). However, the effect of delay in assessment by a rheumatologist on the outcome of RA has scarcely been explored. The purpose of this study was to examine the association between delay in assessment by a rheumatologist, rates of joint destruction, and probability of achieving DMARD-free remission in patients with RA. Patient characteristics associated with components of delay (by the patient, by the general practitioner [GP], and overall) were assessed. Methods. A total of 1,674 early arthritis patients from the Leiden Early Arthritis Clinic cohort were evaluated for patient delay, GP delay, and total delay in assessment by a rheumatologist. Among 598 RA patients, associations between total delay, achievement of sustained DMARD-free remission, and the rate of joint destruction over 6 years followup were determined. Results. The median patient, GP, and total delays in seeing a rheumatologist among patients with early arthritis were 2.4 weeks, 8.0 weeks, and 13.7 weeks, respectively. Among all diagnoses, those diagnosed as having RA or spondylarthritis had the longest total delay (18 weeks). Among the RA patients, 69% were assessed in >= 12 weeks; this was associated with a hazard ratio of 1.87 for not achieving DMARD-free remission and a 1.3 times higher rate of joint destruction over 6 years, as compared with assessment in <12 weeks. Older age, female sex, gradual symptom onset, involvement of the small joints, lower levels of C-reactive protein, and the presence of autoantibodies were associated with longer total delay. Conclusion. Only 31% of the RA patients were assessed in <12 weeks of symptom onset. Assessment in <12 weeks is associated with less joint destruction and a higher chance of achieving DMARD-free remission as compared with a longer delay in assessment. These results imply that attempts to diminish the delay in seeing a rheumatologist will improve disease outcome in patients with RA. Show less
OBJECTIVE:: Recently new classification criteria for Rheumatoid Arthritis (RA) have been devised by methodology that used first a quantitative approach (data from databases), then a qualitative... Show moreOBJECTIVE:: Recently new classification criteria for Rheumatoid Arthritis (RA) have been devised by methodology that used first a quantitative approach (data from databases), then a qualitative approach (consensus-based on paper patients) and finally a common sense based approach (evaluation of the former phases). Now these criteria are being evaluated to assess characteristics of the individual items. This study analyzed characteristics of the item autoantibodies, in particular RF-level. METHODS:: Three separate cohorts with a total of 972 undifferentiated arthritis patients were studied for RA-development (according to the 1987 ACR criteria) and arthritis persistency. Positive and negative predictive values (PPV, NPV) and likelihood ratios (LR) were compared between different levels of RF and the presence of ACPA. A similar comparison was made in 686 RA-patients for the rate of joint destruction during 7 years of follow-up and achievement of sustained-DMARD-free-remission. The variation in RF-levels obtained by different measurement methods in the same RF-positive sera was explored. RESULTS:: Presence of ACPA had a better balance between LR+/LR- and PPV/NPV than high RF-levels for RA-development. The additive value of ACPA assessment after high level RF-testing was higher than vice versa. High level RF was less strongly associated with RA-severity than ACPA-antibodies. The RF-level obtained by different methods in the same patients' sera varied considerably. CONCLUSION:: Level determination of RF is subject to large variation; high level RF has limited additive prognostic value compared to ACPA-positivity. Thus, omitting RF level and using RF-presence, ACPA-presence and ACPA-level may improve the 2010 criteria for RA. Show less
Nies, J.A.B. van; Knevel, R.; Daha, N.; Linden, M.P.M. van der; Gregersen, P.K.; Kern, M.; ... ; Helm-van Mil, A.H.M. van der 2010
Background The presence of anti-citrullinated protein antibodies (ACPA) is a powerful predictive factor for the development and progression of rheumatoid arthritis (RA). The ACPA response has been... Show moreBackground The presence of anti-citrullinated protein antibodies (ACPA) is a powerful predictive factor for the development and progression of rheumatoid arthritis (RA). The ACPA response has been shown to consist of various isotypes, but the consequences of differences in isotype distribution have not been extensively investigated. Objective To investigate the relationship between ACPA isotypes, disease progression and radiological outcome. Methods ACPA isotypes were determined in sera of anti-cyclic citrullinated peptide 2-positive patients by enzyme-linked immunosorbent assay (ELISA). To investigate whether the ACPA response continues to evolve during disease development, the ACPA isotype profile during progression of undifferentiated arthritis (UA) to RA was studied. The association of disease progression with ACPA isotype use was assessed using long-term radiographic follow-up data from patients with RA in two independent cohorts. Results The ACPA isotype distribution did not expand during disease progression from UA to RA, but was relatively stable over time. In both RA cohorts, the baseline ACPA isotype profile was a significant predictor of disease severity, with more isotypes indicating a higher risk of radiographic damage (odds ratio for every additional isotype: 1.4 (95% CI 1.1 to 1.9) p < 0.001). ACPA isotypes supplied additional prognostic information to ACPA status alone, even after correction for other predictive factors. Conclusions The magnitude of the ACPA isotype profile at baseline reflects the risk of future radiographic damage. These results indicate that the presence and the constitution of the ACPA response are relevant to the disease course of RA. Show less
Linden, M.P.M. van der; Boja, R.; Klarenbeek, N.B.; Huizinga, T.W.J.; Heijde, D.M. van der; Helm-van Mil, A.H.M. van der 2010
Background Joint destruction in rheumatoid arthritis (RA) was until recently seen as an irreversible state. Lately, it was found that repair of bone erosions occurs; however, little is known about... Show moreBackground Joint destruction in rheumatoid arthritis (RA) was until recently seen as an irreversible state. Lately, it was found that repair of bone erosions occurs; however, little is known about its prevalence. Objective To investigate the frequency of repair and patients' characteristics associated with repair in an inception cohort. Patients and methods 250 patients with RA, included in the Leiden Early Arthritis Clinic between 1993 and 2000 and treated with conventional disease-modifying antirheumatic drugs, were studied (mean follow-up 10.1 years). Radiographs obtained annually were scored using the Sharp-van der Heijde method, initially aware of the chronology. Patients with a negative change in erosion scores on subsequent radiographs were selected and their series of radiographs were rescored with concealed time sequence by three readers. Repair was defined as agreement between two readers of a negative change in erosion scores that persisted for at least 2 years. Results Repair was identified in 32 joints in 18 patients (7.2%). Patients with repair had a greater prevalence of autoantibodies (rheumatoid arthritis, anti-citrullinated protein antibody) and a higher level of joint destruction. In the joints with repair, arthritis was absent in the 2 years preceding repair. Conclusions Repair occurred in 7.2% of the patients with RA, particularly in clinically inactive joints in patients with severe destructive disease. Show less
Scherer, H.U.; Linden, M.P.M. van der; Kurreeman, F.A.S.; Stoeken-Rijsbergen, G.; Cessie, S. le; Huizinga, T.W.J.; ... ; Toes, R.E.M. 2010
BACKGROUND: /st> Two novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a... Show moreBACKGROUND: /st> Two novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor alpha-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF-kappaB and is involved in inhibiting TNF-receptor-mediated signalling effects. Interestingly, the initial associations were detected in patients with longstanding RA. However, no association was found for rs10499194 in a Swedish cohort with early arthritis. This might be caused by over-representation of patients with severe disease in cohorts with longstanding RA. OBJECTIVE: /st> To analyse the effect of the 6q23 region on the rate of joint destruction. METHODS: /st> Five single nucleotide polymorphisms in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated with progression of radiographic joint damage for a follow-up time of 5 years. RESULTS: /st> Two polymorphisms (rs675520 and rs9376293) were associated with severity of radiographic joint damage in patients positive for anti-citrullinated protein/peptide antibodies (ACPA). Importantly, the effects were present after correction for confounding factors such as secular trends in treatment. CONCLUSIONS: /st> These data associate the 6q23 region with the rate of joint destruction in ACPA+ RA. Show less
Scherer, H.U.; Linden, M.P.M. van der; Kurreeman, F.A.S.; Stoeken-Rijsbergen, G.; Cessie, S. le; Huizinga, T.W.J.; ... ; Toes, R.E.M. 2010
Background Two novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close... Show moreBackground Two novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor a-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF-kappa B and is involved in inhibiting TNF-receptor-mediated signalling effects. Interestingly, the initial associations were detected in patients with longstanding RA. However, no association was found for rs10499194 in a Swedish cohort with early arthritis. This might be caused by over-representation of patients with severe disease in cohorts with longstanding RA. Objective To analyse the effect of the 6q23 region on the rate of joint destruction. Methods Five single nucleotide polymorphisms in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated with progression of radiographic joint damage for a follow-up time of 5 years. Results Two polymorphisms (rs675520 and rs9376293) were associated with severity of radiographic joint damage in patients positive for anti-citrullinated protein/peptide antibodies (ACPA). Importantly, the effects were present after correction for confounding factors such as secular trends in treatment. Conclusions These data associate the 6q23 region with the rate of joint destruction in ACPA+ RA. Show less
