Objectives To assess the relationship between joint tenderness, swelling and joint damage progression in individual joints and to evaluate the influence of treatment on these relationships. Methods... Show moreObjectives To assess the relationship between joint tenderness, swelling and joint damage progression in individual joints and to evaluate the influence of treatment on these relationships. Methods First-year data of the Behandel Strategieen (BeSt) study were used, in which patients recently diagnosed as having rheumatoid arthritis (RA) were randomly assigned into four different treatment strategies. Baseline and 1-year x-rays of the hands and feet were assessed using the Sharp-van der Heijde score (SHS). With generalised estimating equations, 3-monthly assessments of tender and swollen joints of year 1 were related to erosion progression, joint space narrowing (JSN) progression and total SHS progression at the individual joint level (definition >0.5 SHS units) in year 1, corrected for potential confounders and within-patient correlation for multiple joints per patient. Results During year 1, 59% of all 13 959 joints analysed were ever tender and 45% ever swollen, 2.1% showed erosion progression, 1.9% JSN progression and 3.6% SHS progression. Swelling and tenderness were both independently associated with erosion and JSN progression with comparable OR, although with higher OR in the hands than in the feet. Local swelling and tenderness were not associated with local damage progression in patients initially treated with infliximab. Conclusion Clinical signs of synovitis are associated with erosion and JSN progression in individual joints after 1 year in RA. A disconnect between synovitis and joint damage progression was observed at joint level in patients who were treated with methotrexate and infliximab as initial treatment, confirming the disconnect between synovitis and the development of joint damage in tumour necrosis factor blockers seen at patient level. Show less
Guler-Yuksel, M.; Klarenbeek, N.B.; Goekoop-Ruiterman, Y.P.M.; Vries-Bouwstra, J.K. de; Kooij, S.M. van der; Gerards, A.H.; ... ; Lems, W.F. 2010
Introduction: To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA)... Show moreIntroduction: To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years. Methods: In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years. Results: 68% of the patients had accelerated hand BMD loss (>-0.003 g/cm(2)) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage. Conclusions: In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year. Show less
The prognosis of patients with undifferentiated arthritis (UA) may vary from self-limited to severe destructive rheumatoid arthritis (RA). Based on the chance that these patients will develop RA... Show moreThe prognosis of patients with undifferentiated arthritis (UA) may vary from self-limited to severe destructive rheumatoid arthritis (RA). Based on the chance that these patients will develop RA and based on the safety profile of a course of methotrexate for 30-90 days, many clinicians consider using methotrexate in this patient category using the "n of 1" trial principle. During the last few years, more data on interventions in UA have become available that provide guidance in the prescription of drugs to UA patients. Show less
Guler-Yuksel, M.; Allaart, C.F.; Watt, I.; Goekoop-Ruiterman, Y.P.M.; Vries-Bouwstra, J.K. de; Schaardenburg, D. van; ... ; Kloppenburg, M. 2010
OBJECTIVES To investigate the association between systemic and local inflammation and incident and progressive radiographic secondary osteoarthritis (OA) in interphalangeal joints (IPJs) over 3... Show moreOBJECTIVES To investigate the association between systemic and local inflammation and incident and progressive radiographic secondary osteoarthritis (OA) in interphalangeal joints (IPJs) over 3 years in rheumatoid arthritis (RA) patients and the effect of tumor necrosis factor alpha (TNF-α) inhibitor infliximab on secondary OA in IPJs. METHODS In the present observational longitudinal study baseline and 3-year hand X-rays of 416 recent-onset RA patients were scored for osteophytes and erosions in IPJs, blinded for time, using Osteoarthritis Research Society International atlas and Sharp-van der Heijde score. The associations between inflammatory factors and incident and progressive secondary OA in distal IPJs (DIPJs) and proximal IPJs (PIPJs) and the effect of infliximab compared to disease-modifying anti-rheumatic drug treatment on secondary OA were analyzed by multivariable regression and generalised estimating equations analyses. RESULTS Sixty-seven percent of the patients were female with, at baseline, a mean age of 54 years and OA present in DIPJs and PIPJs in 37% and 13%. Three years later, new secondary OA in DIPJs and PIPJs was seen in 11% and 10%, and progressive secondary OA in 36% and 35%. High erythrocyte sedimentation rate over 3 years and progressive erosive damage were risk factors for incident secondary OA in DIPJs, but not in PIPJs. At joint level, progression of erosions was associated with both incident and progressive secondary OA, only in DIPJs. Infliximab treatment was associated with lower incident secondary OA in PIPJs [relative risk 0.5 (95% confidence interval 0.2, 1.0)], independent of decrease in inflammation. CONCLUSION Incident and progressive secondary OA in DIPJs over 3 years was associated with high inflammatory activity in RA. Infliximab treatment reduced incident secondary OA in PIPJs independent of decrease in inflammation, suggesting that anti-TNF-α therapy might be effective against secondary hand OA via other pathways than suppression of inflammation. Further studies in populations of primary hand OA are necessary to determine the role of anti-TNF-α in treatment of primary hand OA. Show less
Guler-Yuksel, M.; Allaart, C.F.; Watt, I.; Goekoop-Ruiterman, Y.P.M.; Vries-Bouwstra, J.K. de; Schaardenburg, D. van; ... ; Kloppenburg, M. 2010
Objectives: To investigate the association between systemic and local inflammation and incident and progressive radiographic secondary osteoarthritis (OA) in interphalangeal joints (IPJs) over 3... Show moreObjectives: To investigate the association between systemic and local inflammation and incident and progressive radiographic secondary osteoarthritis (OA) in interphalangeal joints (IPJs) over 3 years in rheumatoid arthritis (RA) patients and the effect of tumor necrosis factor alpha (TNF-alpha) inhibitor infliximab on secondary OA in IPJs. Methods: In the present observational longitudinal study baseline and 3-year hand X-rays of 416 recent-onset RA patients were scored for osteophytes and erosions in IPJs, blinded for time, using Osteoarthritis Research Society International atlas and Sharp-van der Heijde score. The associations between inflammatory factors and incident and progressive secondary OA in distal IPJs (DIPJs) and proximal IPJs (PIPJs) and the effect of infliximab compared to disease-modifying anti-rheumatic drug treatment on secondary OA were analyzed by multivariable regression and generalised estimating equations analyses. Results: Sixty-seven percent of the patients were female with, at baseline, a mean age of 54 years and OA present in DIPJs and PIPJs in 37% and 13%. Three years later, new secondary OA in DIPJs and PIPJs was seen in 11% and 10%, and progressive secondary OA in 36% and 35%. High erythrocyte sedimentation rate over 3 years and progressive erosive damage were risk factors for incident secondary OA in DIPJs, but not in PIPJs. At joint level, progression of erosions was associated with both incident and progressive secondary OA, only in DIPJs. Infliximab treatment was associated with lower incident secondary OA in PIPJs [relative risk 0.5 (95% confidence interval 0.2, 1.0)], independent of decrease in inflammation. Conclusion: Incident and progressive secondary OA in DIPJs over 3 years was associated with high inflammatory activity in RA. Infliximab treatment reduced incident secondary OA in PIPJs independent of decrease in inflammation, suggesting that anti-TNF-alpha therapy might be effective against secondary hand OA via other pathways than suppression of inflammation. Further studies in populations of primary hand OA are necessary to determine the role of anti-TNF-alpha in treatment of primary hand OA. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
The prognosis of patients with undifferentiated arthritis (UA) may vary front self-limited to severe destructive rheumatoid arthritis (RA). Based on the chance that these patients will develop RA... Show moreThe prognosis of patients with undifferentiated arthritis (UA) may vary front self-limited to severe destructive rheumatoid arthritis (RA). Based on the chance that these patients will develop RA and based on the safety profile of a course of methotrexate for 30-90 days, many clinicians consider using methotrexate in this patient category using the "n of l" trial principle. During the last few years, more data on interventions in UA have become available that provide guidance in the prescription of drugs to UA patients. Show less
Cui, J.; Saevarsdottir, S.; Thomson, B.; Padyukov, L.; Helm-van Mil, A.H.M. van der; Nititham, J.; ... ; Ge 2010
Objective. Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors... Show moreObjective. Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. Methods. A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (Delta DAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. Results. Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the Delta DAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39-0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41-1.99). Conclusion. Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections. Show less
Objectives To develop a matrix model for the prediction of rapid radiographic progression (RRP) in subpopulations of patients with recent-onset rheumatoid arthritis (RA) receiving different dynamic... Show moreObjectives To develop a matrix model for the prediction of rapid radiographic progression (RRP) in subpopulations of patients with recent-onset rheumatoid arthritis (RA) receiving different dynamic treatment strategies. Methods Data from 465 patients with recent-onset RA randomised to receive initial monotherapy or combination therapy were used. Predictors for RRP (increase in Sharp-van der Heijde score >= 5 after 1 year) were identified by multivariate logistic regression analysis. For subpopulations, the estimated risk of RRP per treatment group and the number needed to treat (NNT) were visualised in a matrix. Results The presence of autoantibodies, baseline C-reactive protein (CRP) level, erosion score and treatment group were significant independent predictors of RRP in the matrix. Combination therapy was associated with a markedly reduced risk of RRP. The positive and negative predictive values of the matrix were 62% and 91%, respectively. The NNT with initial combination therapy to prevent one patient from RRP with monotherapy was in the range 2-3, 3-7 and 7-25 for patients with a high, intermediate and low predicted risk, respectively. Conclusion The matrix model visualises the risk of RRP for subpopulations of patients with recent-onset RA if treated dynamically with initial monotherapy or combination therapy. Rheumatologists might use the matrix for weighing their initial treatment choice. Show less
Objective To evaluate the effect of disease activity and antirheumatic treatment on blood pressure (BP) in patients with recent-onset rheumatoid arthritis (RA). Methods 508 patients with RA were... Show moreObjective To evaluate the effect of disease activity and antirheumatic treatment on blood pressure (BP) in patients with recent-onset rheumatoid arthritis (RA). Methods 508 patients with RA were randomised to receive (1) sequential monotherapy, (2) step-up combination therapy, (3) initial combination with prednisone or (4) with infliximab. Systolic and diastolic BP (SBP, DBP), disease activity score (DAS) and body mass index (BMI) were evaluated every 3 months. A linear mixed model was used to model SBP and DBP in each treatment group during year 1, adjusting for baseline BP, changes in BMI, DAS and cardiovascular medication. Results In all groups, mean SBP and DBP were lower for patients with DAS <= 2.4 than for patients with DAS >2.4. In addition, patients initially treated with infliximab (group 4) had a larger decrease in SBP and DBP over time than patients in groups 1-3. The decrease in BP was also observed in patients treated with infliximab after failure on conventional disease-modifying antirheumatic drugs in groups 1-3. The decrease in BP associated with treatment with infliximab occurred irrespective of the DAS response. Conclusion A lower DAS is associated with lower BP. An additional decrease in BP was observed in patients treated with infliximab. Further research is needed to confirm the effect of infliximab on BP. Show less
Aims: Clinical response to methotrexate (MTX) treatment differs among rheumatoid arthritis patients. Genetic variation can partly account for this phenomenon. In this study, functional... Show moreAims: Clinical response to methotrexate (MTX) treatment differs among rheumatoid arthritis patients. Genetic variation can partly account for this phenomenon. In this study, functional polymorphisms in genes related to the mechanism of action of MTX or immunopathogenesis of rheumatoid arthritis were studied for association with treatment outcome in a Dutch cohort of patients with early rheumatoid arthritis. Furthermore, tests for replication of previous research on these genetic variants were performed according to reported end points. Materials & methods: Seven polymorphisms in seven genes were analyzed in 205 genotyped patients with active rheumatoid arthritis. All patients received standardized MTX treatment (<= 25 mg per week orally) combined with folic acid. MTX treatment outcome was evaluated by disease activity score criteria and adverse drug events. The following genetic variants were analyzed and correlated: ABCB1 3435C > T, ITPA IVS2 +21A > C, HLA-G (-14 bp >+14 bp), TGFB1 +869T > C and TLR4 +896A > G. In case of significant differences, regression analyses were applied. Since carriers of the minor alleles of the SNPs DHFR 829C > T and IMPDH2 +787C > T were not observed, no statistical analyses could be performed. Results: No significant associations or replications of these genetic variants with MTX efficacy were demonstrated. Regarding toxicity, patients carrying the ABCB1 3435T-allele and TLR4 +896G-allele were 2.5-times more likely to develop adverse drug events at 6 months (odds ratio: 2.6; 95% CI: 1.1-6.2, and odds ratio: 2.5; 95% CI: 1.1-6.1, respectively). Additionally, this chance increased almost fourfold in patients with the two unfavorable genotypes (odds ratio: 3.9; 95% CI: 1.5-10.3). However, none of these associations remained significant after correction for multiple testing (p < 0.004). Conclusion: Our data indicate that MTX toxicity was potentially associated with ABCB1 3435C > T and TLR4 +896A > G. However, after correction, none of these associations remained significant. Furthermore, no significant associations or replications of these functional variants with efficacy were found. Show less
Objectives: To compare the efficacy of Disease Activity Score (DAS)-driven therapy and routine care in patients with recent-onset rheumatoid arthritis. Methods: Patients with recent-onset... Show moreObjectives: To compare the efficacy of Disease Activity Score (DAS)-driven therapy and routine care in patients with recent-onset rheumatoid arthritis. Methods: Patients with recent-onset rheumatoid arthritis receiving traditional antirheumatic therapy from either the BeSt study, a randomised controlled trial comparing different treatment strategies (group A), or two Early Arthritis Clinics (group B) were included. In group A, systematic DAS-driven treatment adjustments aimed to achieve low disease activity (DAS <= 2.4). In group B, treatment was left to the discretion of the treating doctor. Functional ability (Health Assessment Questionnaire (HAQ)), Disease Activity Score in 28 joints (DAS28) and Sharp/van der Heijde radiographic score (SHS) were evaluated. Results: At baseline, patients in group A (n=234) and group B (n=201) had comparable demographic characteristics and a mean HAQ of 1.4. Group A had a longer median disease duration than group B (0.5 vs 0.4 years, p=0.016), a higher mean DAS28 (6.1 vs 5.7, p<0.001), more rheumatoid factor-positive patients (66% vs 42%, p<0.001) and more patients with erosions (71% vs 53%, p<0.001). After 1 year, the HAQ improvement was 0.7 vs 0.5 (p=0.029), and the percentage in remission (DAS28<2.6) 31% vs 18% (p<0.005) in groups A and B, respectively. In group A, the median SHS progression was 2.0 (expected progression 7.0), in group B, the SHS progression was 1.0 (expected progression 4.4). Conclusions: In patients with recent-onset rheumatoid arthritis receiving traditional treatment, systematic DAS-driven therapy results in significantly better clinical improvement and possibly improves the suppression of joint damage progression. Show less
