Validity of single variables and composite indices for measuring disease activity in rheumatoid arthritis.

Objective. To determine whether the tumor necrosis factor ␣ (TNFA) -308 guanine-to-adenosine polymorphism and/or the shared epitope (SE) is associated with radiographic damage in patients with early rheumatoid arthritis (RA).Methods. The cohort consisted of 189 patients with early seropositive RA (median 5.6 months since symptom onset) who had active disease, no previous disease-modifying antirheumatic drug treatment, and >2 sets of scored radiographs of the hands/wrists and forefeet. TNFA -308 polymorphism was analyzed by polymerase chain reaction pyrosequencing. The SE was defined as presence of any 1 of the following HLA-DRB1 alleles: *0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001, *1402, or *1406. Radiographic progression was assessed by the total Sharp score.Results. Using a weighted least-squares regression analysis, patients with the -308 TNFA AA plus AG genotypes (n ‫؍‬ 49) had significantly higher rates of progression in erosion scores (median 0.84 versus 0.48 units/year), joint space narrowing (JSN) scores (0.42 versus 0.04), and total Sharp scores (1.70 versus 0.61) compared with patients with the TNFA GG genotype (n ‫؍‬ 140). Presence of the SE (n ‫؍‬ 137) was associated with significantly lower progression rates (per year) for total Sharp scores (median 0.9 versus 1.25 units/year) and JSN scores (0.04 versus 0.41), but not for erosion scores (0.50 versus 0.61) compared with patients without the SE (n ‫؍‬ 52). In a least-squares multiple linear regression model, the presence of the AA plus AG genotypes was associated with a significantly higher progression rate after adjusting for the presence of the SE, interaction between the SE and the AA plus AG genotypes, baseline log C-reactive protein level, Health Assessment Questionnaire Disability Index, total Sharp score, swollen joint count, and presence of osteophytes (osteoarthritis). There was a strong linkage disequili-

Section: Methodsmentioning

confidence: 99%

Association of tumor necrosis factor α polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort

Khanna

Park

et al. 2006

“…Radiographs obtained during the study were scored according to the modified Sharp method (34). Disease activity in the RA patients was measured using the Disease Activity Score (DAS), a validated composite score incorporating tender and swollen joint counts, ESR, and a patient global assessment of disease activity (100-mm visual analog scale) (35). A DAS of Յ1.6 indicates remission, while a value of Ն4.3 suggests active disease (35).…”

Section: Methodsmentioning

confidence: 99%

Screening for atherosclerosis in patients with rheumatoid arthritis: Comparison of two in vivo tests of vascular function

Doornum¹,

McColl²,

Jenkins³

et al. 2003

127

Objective. Inflammation appears to play a central role in atherosclerosis, and endothelial damage mediated by systemic inflammation may contribute to the increased cardiovascular mortality in rheumatoid arthritis (RA). Brachial artery flow-mediated dilatation (FMD) and pulse wave analysis (PWA) are measures of vascular function. The aim of this study was to determine if FMD and PWA are abnormal in patients with RA.Methods. Twenty-five RA patients and 25 matched healthy controls were studied. All were free of traditional cardiovascular risk factors. FMD was measured in all subjects. PWA was performed in 18 RA patients and 18 controls, with results expressed as large and small artery compliance (C1 and C2). Modified Sharp scores were calculated in 13 RA patients.Results. Results (mean ؎ SD) in RA patients and controls, respectively, were as follows: FMD 107.6 ؎ 4.6% versus 108.5 ؎ 4.1% (P ‫؍‬ 0.49), C1 14.8 ؎ 2.8 ml/mm Hg ؋ 10 versus 17.9 ؎ 3.1 ml/mm Hg ؋ 10 (P ‫؍‬ 0.0033), C2 4.5 ؎ 2.3 ml/mm Hg ؋ 100 versus 7.7 ؎ 3.7 ml/mm Hg ؋ 100 (P ‫؍‬ 0.0039). There was an inverse correlation between C2 and modified Sharp scores in the RA patients (Spearman's rho -0.69, P ‫؍‬ 0.0085).Conclusion. FMD was normal in these RA patients, whereas arterial compliance was markedly reduced. PWA appears to be a more sensitive measure of vascular dysfunction than FMD in RA and may be the preferred surrogate marker of vascular dysfunction in longitudinal studies of RA patients. The inverse correlation between C2 and the modified Sharp score, a measure that reflects disease activity over time, supports the notion that chronic inflammation plays a role in RA-associated atherosclerosis.

“…For these reasons, a clear assessment of a patient's overall disease activity and responses to treatment modifications is important. However, single measures do not comprise all aspects of RA activity and might not be useful for monitoring patients because of the variability of the presentation and course of RA (5,12).…”

mentioning

confidence: 99%

Remission and active disease in rheumatoid arthritis: Defining criteria for disease activity states

Aletaha¹,

Ward²,

Machold³

et al. 2005

480

338

Objective. Several composite scores are available to assess the activity of rheumatoid arthritis (RA). Criteria for remission and active RA based on these continuous scores are important for use in clinical practice and clinical trials. We aimed to reevaluate or to define such criteria for the Disease Activity Score in 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI).Methods. We sampled patient profiles from an observational RA database that included clinical and laboratory variables. Thirty-five rheumatology experts classified these profiles into 1 of 4 categories: remission, low, moderate, or high disease activity. Cutoff values were estimated by mapping scores on the DAS28 and SDAI to these ratings, and analyses of agreement (kappa statistics) and a diagnostic testing approach (receiver operating characteristic curves) were used to validate the estimates. The final criteria were validated using 2 observational cohorts (a routine cohort of 767 patients and an inception cohort of 91 patients).Results. Results from the 3 analyses were very similar and were integrated. The criteria for separating remission, low, moderate, and high disease activity based on the SDAI were scores of 3.3, 11, and 26, respectively; those based on the DAS28 were scores of 2.4, 3.6, 5.5, respectively. In the routine cohort, these cutoff values showed substantial agreement (weighed ‫؍‬ 0.70) and discriminated between groups of patients with clearly different functional capacities (P < 0.001). In the inception cohort, these cutoff scores differentiated responders (those with a 20% response on the American College of Rheumatology improvement criteria) from nonresponders (P < 0.01), as well as patients with and without radiologic progression (P < 0.05).Conclusion. New criteria for levels of RA disease activity were determined and internally validated. These criteria, which are based on current and explicit expert judgment, are valuable in this era of rapidly advancing therapeutic approaches.