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ABSTRACT: OBJECTIVES.: Matrix-based risk models have been proposed as a tool to predict rapid radiographic progression (RRP) in rheumatoid arthritis (RA), but the experience with such models is limited. We tested the performance of three risk models for RRP in an observational cohort. METHODS.: Subjects from an observational RA cohort with hand radiographs and necessary predictor variables to be classified by the risk models were identified (n=478). RRP was defined as a yearly change in van der Heijde-Sharp score of ò 5 units. Patients were placed in the appropriate matrix categories, with a corresponding predicted risk of RRP. The mean predicted probability for cases and non-cases, integrated discrimination improvement, Hosmer-Lemeshow statistics and the c-statistics were calculated. RESULTS.: The median (IQR) age was 59 (50, 66) years, disease duration 12 (4, 23) years and swollen joint count 6 (2, 13), 84% were female and 86% had erosions at baseline. Twelve percent (32/271) of patients treated with synthetic DMARDs at baseline and 10% (21/207) of patients treated with biologic DMARDs experienced RRP. Most of the predictor variables had a skewed distribution in the population. All models had a suboptimal performance when applied to the BRASS cohort, with c-statistics of 0.59 (model A), 0.65 (model B) and 0.57 (model C) and Hosmer-Lemeshow chi-square p-values of 0.06 (model A), 0.005 (model B) and 0.05 (model C). CONCLUSION.: Matrix risk models developed in clinical trials of patients with early RA had limited ability to predict RRP in this observational cohort of RA patients. © 2012 by the American College of Rheumatology.
Arthritis care & research. 10/2012;
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Siri Lillegraven,
Femke H M Prince,
Nancy A Shadick,
Vivian P Bykerk,
Bing Lu, Michelle L Frits,
Christine K Iannaccone,
Tore K Kvien,
Espen A Haavardsholm,
Michael E Weinblatt,
Daniel H Solomon
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ABSTRACT: One goal of remission in rheumatoid arthritis (RA) is to halt joint damage. The authors assessed the progression of radiographic joint damage among RA patients in remission by the new ACR/EULAR criteria (Boolean approach) compared with remission thresholds for the simplified disease activity index (SDAI), clinical disease activity index (CDAI) and disease activity score based on 28 joints and C-reactive protein (DAS28-CRP) in an observational cohort, and evaluated the relationship between time in remission and radiographic joint damage.
535 RA patients underwent physical examination and laboratory assessment at baseline, 1 and 2 years. Radiographs at baseline and 2 years were scored by the van der Heijde modified Sharp score (TSS). Positive likelihood ratios for a good radiographic outcome (change in TSS <1 unit/year) were calculated for each of the remission criteria. Radiographic progression was compared between patients in remission at none, one, two and three visits by χ(2) goodness of fit statistics.
20% of patients in ACR/EULAR remission at baseline had radiographic progression, 24% in SDAI remission, 19% in CDAI remission and 30% of patients in DAS28-CRP remission. The positive likelihood ratio for good radiographic outcome was 2.6 for ACR/EULAR criteria, 2.1 for SDAI, 2.8 for CDAI and.1.5 for DAS28-CRP. Reduced radiographic progression was observed for patients with an increasing number of visits in remission (p<0.003 for all criteria, χ(2) goodness of fit statistics).
Patients with RA in remission by any established criteria can experience radiographic progression. An increased number of visits in remission was associated with reduced radiographic damage.
Annals of the rheumatic diseases 10/2011; 71(5):681-6. · 8.11 Impact Factor
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ABSTRACT: Disease remission has become a feasible goal for most rheumatoid arthritis (RA) patients; however, patient-reported symptoms, such as pain, may persist despite remission. We assessed the prevalence of pain in RA patients in remission according to the Disease Activity Score (DAS28-CRP4) and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria.
Data were analyzed from RA patients in the Brigham Rheumatoid Arthritis Sequential Study with data at baseline and 1 year. DAS28 remission was defined as DAS28-CRP4 <2.6. The ACR/EULAR remission criteria included (a) one or more swollen joints, (b) one or more tender joints, (c) C-reactive protein ≤1 mg/dl, and (d) patient global assessment score ≤1. Pain severity was measured by using the pain score from the Multi-Dimensional Health Assessment Questionnaire (MDHAQ). The associations between baseline clinical predictors and MDHAQ pain at baseline and 1 year were assessed by using multivariable linear regression.
Among the 865 patients with data at baseline and 1 year, 157 (18.2%) met DAS28-CRP4 remission criteria at both time points. Thirty-seven (4.3%) met the ACR/EULAR remission criteria at baseline and 1 year. The prevalence of clinically significant pain (MDHAQ pain ≥4) at baseline ranged from 11.9% among patients meeting DAS28-CRP4 remission criteria to none among patients meeting ACR/EULAR remission criteria. Patient global assessment, MDHAQ function, MDHAQ fatigue, MDHAQ sleep, and arthritis self-efficacy were significantly associated with MDHAQ pain in cross-sectional (P ≤ 0.0005) and longitudinal analyses (P ≤ 0.03). Low swollen-joint counts were associated with high MDHAQ pain in longitudinal analyses (P = 0.02) but not cross-sectional analyses. Other measures of inflammatory disease activity and joint damage were not significantly associated with MDHAQ pain at baseline or at 1 year.
Clinically significant pain continues among a substantial proportion of patients in DAS28 remission but not among those in ACR/EULAR remission. Among patients in DAS28 remission, patient global assessment, disability, fatigue, sleep problems, and self-efficacy are strongly associated with pain severity at baseline and 1 year, whereas inflammatory disease activity and joint damage are not significantly associated with elevated pain severity at either baseline or 1 year.
Arthritis research & therapy 06/2011; 13(3):R83. · 4.27 Impact Factor
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ABSTRACT: The objective of this review is to report on the progress of the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) Registry data collection and summarize previous research in understanding therapeutic response to DMARDs using clinical and genetic data. The BRASS Registry, established in 2003, is a large, single-centre, prospective and observational cohort of 1100 RA patients. Patients with either new-onset or established RA disease are recruited from the practices of rheumatologists. Annual visits collect information on demographics, 28-joint DAS-CRP3 (DAS-28-CRP3), medication use, comorbidities and functional status (Modified Health Assessment Questionnaire, Short Form Health Survey 12). Two published studies have utilized BRASS to examine genetic predictors of treatment response. In a cross-sectional study, examining the association between candidate single nucleotide polymorphisms (SNPs) and disease activity in a subset of 120 RA patients on MTX monotherapy, the minor allele of ATIC rs4673993 was associated with low disease activity (P=0.01, DAS-28-CRP3≤3.2). In an international collaboration, 55 BRASS patients receiving anti-TNF therapy were genotyped for 31 SNPs associated with the risk of RA. With our collaborators, we discovered an SNP at the protein tyrosine phosphatase, receptor type, C (PTPRC) gene locus that was associated with EULAR 'good response'. With accurate data collection and the capacity to run genome-wide association studies and SNP analyses, the BRASS Registry has the ability to determine the contribution of genetic variants to disease onset and to assess their usefulness as biomarkers for treatment response and drug toxicity.
Rheumatology (Oxford, England) 01/2011; 50(1):40-6. · 4.24 Impact Factor
