OBJECTIVE\nTo determine whether a multibiomarker disease activity (MBDA) score predicts radiographic damage progression in the subsequent year in patients with early rheumatoid arthritis.\nMETHODS... Show moreOBJECTIVE\nTo determine whether a multibiomarker disease activity (MBDA) score predicts radiographic damage progression in the subsequent year in patients with early rheumatoid arthritis.\nMETHODS\nThere were 180 serum samples available in the BeSt study (trial numbers NTR262, NTR 265): 91 at baseline (84 with radiographs available) and 89 at 1-year followup (81 with radiographs available). Radiographs were assessed using the Sharp/van der Heijde Score (SvdH). Twelve serum biomarkers were measured to determine MBDA scores using a validated algorithm. Receiver-operating curves and Poisson regression analyses were performed, with Disease Activity Score (DAS) and MBDA score as independent variables, and radiographic progression as dependent variable.\nRESULTS\nAt baseline, MBDA scores discriminated more between patients who developed radiographic progression (increase in SvdH ≥ 5 points) and patients who did not [area under the curve (AUC) 0.767, 95% CI 0.639-0.896] than did DAS (AUC 0.521, 95% CI 0.358-0.684). At 1 year, MBDA score had an AUC of 0.691 (95% CI 0.453-0.929) and DAS had an AUC of 0.649 (95% CI 0.417-0.880). Adjusted for anticitrullinated protein antibody status and DAS, higher MBDA scores were associated with an increased risk for SvdH progression [relative risk (RR) 1.039, 95% CI 1.018-1.059 for baseline MBDA score; 1.037, 95% CI 1.009-1.065 for Year 1 MBDA score]. Categorized high MBDA scores were also correlated with SvdH progression (RR for high MBDA score at baseline 3.7; low or moderate MBDA score as reference). At 1 year, high MBDA score gave a RR of 4.6 compared to low MBDA score.\nCONCLUSION\nMBDA scores predict radiographic damage progression at baseline and during disease course. Show less
Objective. To determine the prevalence of large-joint damage and the association with small-joint damage in patients with RA after 8 years of low DAS (≤2.4)-targeted treatment with different... Show moreObjective. To determine the prevalence of large-joint damage and the association with small-joint damage in patients with RA after 8 years of low DAS (≤2.4)-targeted treatment with different treatment strategies.Methods. Radiological data of 290 patients participating in the BeSt study, a randomized trial comparing initial monotherapy and initial combination therapy strategies, were used. Radiographs of large joints were scored using the Larsen score and of the small joints using the Sharp-van der Heijde score. With multivariate logistic regression analysis, an association between total damage of the small joints and of the large joints was investigated.Results. After 8 years of treatment, damage was observed in 12% of shoulders, 10% of elbows, 26% of wrists, 13% of hips, 18% of knees and 7% of the ankles. Damage in one or more large joints was found in 64% of patients, with a median score of 1. No difference was found between initial monotherapy or combination therapy strategies. There was a significant association between damage progression in small joints and damage to one or more large joints (OR 1.02; 95% CI 1.00-1.04).Conclusion. After 8 years of DAS-targeted treatment in early RA patients, large-joint damage was found in 64% of patients and was associated with small-joint damage. Continued DAS-targeted treatment is probably more important in damage suppression than initial treatment strategy. Patients with more damage to hands and feet also have more damage to the large joints. Show less
Broek, M. van den; Dirven, L.; Klarenbeek, N.B.; Molenaar, T.H.E.; Han, K.H.; Kerstens, P.J.S.M.; ... ; Allaart, C.F. 2012
Objective: Personalized treatment depends on the treatment goals. Current prediction models to guide initial treatment choices focus on radiological damage progression. However, for some patients... Show moreObjective: Personalized treatment depends on the treatment goals. Current prediction models to guide initial treatment choices focus on radiological damage progression. However, for some patients this outcome is less relevant, whereas short-term functional ability is relevant to all. Do these various treatment goals share the same predictors? Methods: Data for 497 patients from the Dutch Behandel Strategieen (BeSt) study of treatment strategies for early rheumatoid arthritis (RA), randomized to initial monotherapy or combination therapy, were used. Predictors of short-term functional disability [Health Assessment Questionnaire (HAQ) score ≥ 1 after 3 months of treatment] were identified with logistic regression analyses. Predicted risks of a HAQ score ≥ 1 were determined for each treatment group and for each subpopulation. Results: At baseline, 76% of patients had a HAQ score ≥ 1 (mean 1.7 ± 0.5). After 3 months of treatment this score was achieved by 40% (mean HAQ score 1.5 ± 0.5). Baseline HAQ score, pain, the Ritchie Articular Index (RAI), and treatment group were significant independent predictors for a HAQ score ≥ 1; the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and baseline radiological damage were not. With cut-offs of 35% and 60%, the risk of a HAQ score ≥ 1 was high for 47% and low for 20% of the patients treated with initial monotherapy. Risks were markedly reduced in the combination therapy groups, also in unfavourable risk profiles. Conclusion: In recent-onset active RA, baseline HAQ score, pain, and initial treatment are predictors for a HAQ score ≥ 1 after 3 months. Known predictors of radiological damage were not predictive of short-term functional disability. The choice of the best initial treatment thus depends on the relevance of various outcome measures for an individual patient. Show less
Broek, M. van den; Dirven, L.; Klarenbeek, N.B.; Molenaar, T.H.E.; Han, K.H.; Kerstens, P.J.S.M.; ... ; Allaart, C.F. 2011
OBJECTIVE: Anticitrullinated protein antibodies (ACPAs) are suggested to identify different subsets of patients with rheumatoid arthritis (RA). The authors compared the clinical and radiological... Show moreOBJECTIVE: Anticitrullinated protein antibodies (ACPAs) are suggested to identify different subsets of patients with rheumatoid arthritis (RA). The authors compared the clinical and radiological responses to Disease Activity Score (DAS)-steered treatment in patients with RA positive or RA negative for ACPA.METHODS: In the BehandelStrategieën (BeSt) study, 508 patients with recent-onset RA were randomised to four treatment strategies aimed at a DAS ≤2.4. Risks of damage progression and (drug-free) remission in 8 years were compared for ACPA-positive and ACPA-negative patients using logistic regression analysis. Functional ability and DAS components over time were compared using linear mixed models.RESULTS: DAS reduction was achieved similarly in ACPA-positive and ACPA-negative patients in all treatment strategy groups, with a similar need to adjust treatment because of inadequate response. Functional ability and remission rates were not different for ACPA-positive and ACPA-negative patients. ACPA-positive patients had more radiological damage progression, especially after initial monotherapy. They had a lower chance of achieving (persistent) drug-free remission.CONCLUSION: Clinical response to treatment was similar in ACPA-positive and ACPA-negative patients. However, more ACPA-positive patients, especially those treated with initial monotherapy, had significant radiological damage progression, indicating that methotrexate monotherapy and DAS- (≤2.4) steered treatment might be insufficient to adequately suppress joint damage progression in these patients. Show less
