Time-averaged Disease Activity Research Articles

Disease activity of rheumatoid arthritis and kidney function decline: a large prospective registry study

IntroductionChronic kidney disease (CKD) is a common comorbidity of rheumatoid arthritis (RA). The association of longitudinal RA disease activity with long-term kidney function has remained uncertain.MethodWe analysed a multicentre prospective...

Baseline bony erosions and time-averaged DAS28 predict discontinuation of TNF inhibitors in rheumatoid arthritis

The present study evaluated the predictive role of baseline radiographic change and disease activity on drug retention and clinical response in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitor (TNFi). Korean Observational Study Network for Arthritis (KORONA) registry was evaluated to identify RA patients treated with a TNFi. Disease activity score-28 (DAS28) was evaluated at baseline and 1 year after TNFi initiation or at termination of TNFi due to inefficacy (within 1 year). The retention rate of TNFi was compared in patients with and without bony erosions. The hazard ratio (HR) for drug retention was evaluated by Cox regression analysis, as was the odds ratio (OR) for achieving remission (DAS28 < 2.6). This study included 109 RA patients, including 97 (89%) women and 30 (27.5%) with erosions, who were treated with a TNFi. Higher baseline DAS28 was negatively associated with achievement of remission (OR = 0.56, 95% CI 0.35–0.88). The TNFi retention rate was significantly lower in RA patients with than in those without erosions (p = 0.04). Factors significantly associated with drug discontinuation included the presence of erosions (HR = 2.45, 95% CI 1.08–5.51) and higher time-averaged DAS28 (HR = 2.17, 95% CI 1.47–3.20), whereas concomitant methotrexate was associated with lack of drug discontinuation (HR = 0.40, 95% CI 0.17–0.95). The presence of erosions and high time-averaged disease activity could predict poor retention of TNFi by RA patients. Higher baseline DAS28 was associated with a reduced clinical response in patients with RA.Trial registration Clinical Research Information Service of South Korea https://cris.nih.go.kr: KCT0000086, registered May 26, 2009.

Time-averaged DAS28 and HAQ predict cardiovascular disease in patients with rheumatoid arthritis: Data from KORONA registry.

To evaluate the predictive role of time-averaged disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ) on cardiovascular disease (CVD) events in patients with rheumatoid arthritis (RA). Patients with RA were recruited from 23 tertiary hospitals. Baseline and annual follow-up data of demographic, laboratory, questionnaire, RA-associated parameters, and occurrence of CVD were collected. Patients were divided into three groups according to time-averaged DAS28: 1) remission (&lt;2.6), 2) low (2.6-3.2), 3) moderate (3.2-5.1), and 4) high (&gt;5.1). Kaplan-Meier curves was performed to compare the cumulative probability of CVD. Hazard ratios of each factor on the occurrence of CVD were obtained using Cox regression analyses. A total of 4,034 RA patients with 826 for remission, 938 for low, 2,002 for moderate, and 268 for high time-averaged DAS28 groups were included. Baseline age, disease duration, ESR, CRP, DAS28, and HAQ scores were higher in the high time-averaged DAS28 group. The incidence rate of CVD was 2.86, 2.71, 3.53, and 8.13 events per 1,000 person-years for the remission, low, moderate, and high time-averaged DAS28 groups, respectively. The incidence rate ratio of CVD in the high time-averaged DAS28 group were 3.01 (95% CI 1.20-8.50) when compared to low time-averaged DAS28 group. The cumulative hazard for CVD in the high time-averaged DAS28 group was significantly high (log-rank P&lt;0.01). In multivariate Cox regression analysis, age, high time-averaged DAS28, and time-averaged HAQ&gt;0.5, were positively associated with CVD events in RA patients. In patients with RA, time-averaged DAS28 and HAQ could predict the occurrence of CVD. Clinical Research Information Service of South Korea https://cris.nih.go.kr: KCT0000086, registered May 26, 2009.

Disease activity as a risk factor for venous thromboembolism in rheumatoid arthritis analysed using time-averaged DAS28CRP: a nested case-control study.

The objective of this study is to clarify the clinical features and risk factors of venous thromboembolism (VTE) in patients with rheumatoid arthritis (RA). We retrospectively reviewed the prevalence of VTE in RA patients who visited Hokkaido University Hospital from 2010 to 2019 and had more than 2years of follow-up. To explore the risk to develop VTE, we selected 260 RA patients without VTE (non-VTE) via density sampling and identified the risk factors for VTE by multivariate logistic regression analysis. Univariate conditional logistic regression analysis showed older age (p < 0.0001, Odds Ratio [OR] 1.08, 95% Confidence Interval [CI] 1.04-1.14), increase of the body mass index (BMI) (p = 0.001, OR 1.17, 95% CI 1.06-1.31), higher prevalence of RA-associated lung disease (p = 0.002, OR 2.10, 95% CI 1.33-3.30) and more frequent glucocorticoid usage (p = 0.001, OR 2.09, 95% CI 1.34-3.51) in RA patients was associated with the development of VTE significantly. Furthermore, patients with higher time-averaged disease activity score 28 (DAS28) CRP were at elevated risk (p < 0.0001, OR 3.25, 95% CI 1.94-6.12). In conditional multivariate logistic regression analysis, time averaged DAS28CRP was significantly associated with the development of VTE (p = 0.0001, adjusted OR 3.40, 95% CI 1.77-7.85). Disease activity was identified as a major risk factor of VTE in patients with RA, suggesting that sustained clinical remission could be beneficial for decrease the risk of VTE.

Time-averaged disease activity of rheumatoid arthritis associated with long-term bone mineral density changes.

Background:Rheumatoid arthritis (RA) is associated with poor bone mineral density (BMD). We designed the current study owing to the lack of long-term prospective studies regarding whether a high disease activity leads to increased bone loss.Methods:We have continually enrolled patients with RA. According to the average disease activity score in 28 joints based on the erythrocyte sedimentation rate (DAS28-ESR) during follow-up, the patients were classified into remission, low disease activity, and moderate or high disease activity groups. Patients were examined with dual-energy X-ray absorptiometry at baseline and after 3 years of follow-up. BMD changes were compared among the groups.Results:We have studied 477 patients. Overall BMD was significantly reduced from baseline to the 3-year follow-up (p < 0.05). After stratifying according to the time-averaged DAS28-ESR levels and use of anti-osteoporosis treatment (AOT), the BMD values of the femur and spine significantly increased in patients in the remission group with AOT. The BMD changes of different DAS28-ESR patients were further compared using the generalized estimation equation model. For the patients on AOT, the negative change in femoral BMD values of the moderate or high activity group was significant when compared with the remission group with positive BMD changes (regression coefficient, –0.038; 95% confidence interval, –0.055 to –0.021).Conclusion:For RA patients, if remission is achieved, AOT can better improve BMD, especially in the femur. In addition, moderate or high disease activity will lead to significant bone loss; therefore, disease activity must be actively controlled.

Treatment of rheumatoid arthritis: csDMARDS versus bDMARDS. Prospective study to evaluate disease activity

The assessment of disease activity is an essential component in the selection of therapeutic approach for the prevention of disability of patients with RA. The current study was conducted to evaluate the disease activity in patients on csDMARDs and bDMARDs after 6 months to 1-year of treatment and to determine whether the benefits of different therapies were sustained over time. For the purpose of the study were selected 220 patients with a mean age 55.05 ± 10.63 SD years, meeting the 1987 ACR classification criteria for RA. Patients were stratified according to treatment regimens into 2 age-matched treatment groups: 96 on csDMARDs and 124 on bDMARD therapy. Patient‘s assessment of disease related pain, global health and physician assessment of global health was made by visual analogue scale (VAS) – 100 mm. Disease activity was the primary outcome domain. Independent joint assessor evaluated 28 joints on baseline, 6th and 12th month of the follow-up period. C-reactive protein (CRP) was used to measure the infl ammation process. DAS28-CRP, CDAI and SDAI were calculated according to the standard formulas. Comparison was performed by analysis variance ANOVA. On baseline, patients on bDMARDs had a significantly higher mean time-averaged 28-joint disease activity score (5.03 ± 0.84 SD vs. 4.35 ± 1.20 SD, p &lt; 0,001), CDAI (25.06 ± 7.32 SD vs. 20.83 ± 10.53 SD, p &lt; 0.001) and SDAI (28.27 ± 8.74 SD vs. 23.19 ± 11.89 SD, p &lt; 0.001) compared to those on csDMARDs. On the 6th month in both groups (bDMARDS and csDMARDs) we found significant decrease in mean DAS28 (p &lt; 0.001, p &lt; 0.001), although no significant difference in disease activity between the groups was measured by this indicator (3.75 ± 2.49 SD vs 3.90 ± 1.10 SD, p = 0.566). Patients on bDMARDs had significantly lower disease activity compared to those on csDMARDs after 6th and 12th month of treatment assessed by CDAI (13.43 ± 4.98 SD vs 16.81 ± 9.94 SD, p = 0.001; 8.65 ± 4.53 SD vs 15.86 ± 10.02 SD, p &lt; 0.001), and SDAI (14.63 ± 5.42 SD vs 18.38 ± 10.49 SD, p &lt; 0.001; 9.39 ± 4.92 SD vs 16.79 ± 10.5 SD, p &lt; 0.001). Unlike results reported by DAS28-CRP which showed no change between the 6th and 12th month in patients receiving csDMARDs (3.90 ± 1.10 SD, 3.82 ± 1.12 SD, p = 0.156), we observed a statistically significant difference in all three time intervals (0, the 6th, 10th month) of the follow up period regarding to CDAI and SDAI. After a year prospective follow-up, therapy with biologic DMARDs results in sustained suppression – minimal disease activity assessed by DAS28-CRP, CDAI and SDAI, compared to patients receiving DMARDs who had moderate disease activity according to these tools. The therapy with bDMARDs was superior to csDMARDs therapy for suppressing disease activity (assessed by DAS28-CRP, CDAI and SDAI) of rheumatoid arthritis (RA) on the 6th and 12th month of the follow-up period.

Inhibition of radiographic progression in psoriatic arthritis by adalimumab independent of the control of clinical disease activity.

ObjectivesTo evaluate the relationship between radiographic progression and disease activity in subjects with PsA treated with adalimumab (ADA) or placebo (PBO) and the impact of concomitant MTX.MethodsThis was a post hoc analysis of the randomized, double-blind, PBO-controlled ADEPT trial. Subjects were categorized according to time-averaged (TA) disease activity (remission, low, moderate or high) based on Disease Activity Score of 28 joints with CRP [DAS28(CRP)], Disease Activity Index for Psoriatic Arthritis (DAPSA) or Psoriatic Arthritis Disease Activity Score (PASDAS), and achievement of minimal disease activity (MDA) at week 24. Radiographic progression was assessed as change in modified total Sharp score (ΔmTSS) from baseline to week 24. The analyses included interaction terms between disease activity and treatment on radiographic progression, comparison of radiographic progression in subjects categorized by disease activity and treatment, and correlation between disease activity and radiographic progression by treatment.ResultsThe interaction terms for TA disease activity and treatment on ΔmTSS were significant (P = 0.002–0.008). Irrespective of concomitant MTX, ΔmTSS was lower with ADA vs PBO in all disease activity categories. Importantly, even in subjects having moderate or high disease activity or not achieving MDA, ΔmTSS was significantly lower on ADA than PBO (P = 0.05–0.001 for TA-DAPSA, TA-PASDAS and MDA). Correlations between TA disease activity scores and ΔmTSS were moderately positive and significant (P < 0.001) with PBO but non-significant with ADA.ConclusionAmong subjects with PsA treated with ADA, there was evidence of a ‘disconnect’ between disease activity and radiographic progression: inhibition of radiographic progression was greater than expected based on control of clinical disease activity alone. MTX had no added effect.Trial registrationClinicalTrials.gov, http://clinicaltrials.gov, NCT00646386.

Pediatric Systemic Lupus Erythematosus: Learning From Longer Follow Up to Adulthood.

Background: Pediatric systemic lupus erythematosus (pSLE) is a rare condition, representing approximately 10% of SLE cases. The aim of this study was to identify variables to improve the diagnostic awareness and management of pSLE patients.Methods: This retrospective study included 25 patients diagnosed with pSLE and followed at the University of Pisa. We collected data about clinical profile at disease onset and during a long-term follow-up, including disease activity, organ damage development, and treatments received.Results: The mean patient age at disease onset was 14.6 ± 1.6 years, and the mean follow-up period was 14.17 ± 8.04 years. The most common initial manifestations were arthritis, malar rash, and cytopenias. The median time to diagnosis since the first symptoms was 6 months, and was significantly longer in patients with hematological onset (54 months). During follow-up, the number of patients with renal involvement showed a significant increase, from 36% at diagnosis to 72.2% after 10 years of disease evolution. Patients who developed chronic organ damage maintained a higher time-averaged disease activity during follow-up and received a significantly higher dose of corticosteroids.Conclusion: Patients with immune cytopenia represent a group deserving strict clinical follow-up for the risk of evolution to SLE. Intense surveillance of renal function, early treatment and steroid-sparing strategies should be strongly considered in the management of pSLE patients.

Time-averaged disease activity fits better joint destruction in rheumatoid arthritis

Disease activity of rheumatoid arthritis (RA), evaluated as Disease Activity Score (DAS), is associated with joint destruction. Since joint destruction reflects the history of disease activities, we hypothesized that time-averaged disease activity would better correlate with joint destruction than one-time disease activity. We recruited RA patients in IORRA (n = 557) and KURAMA (n = 204) cohorts, and calculated time-averaged DAS28 to model a modified Sharp/van der Heijde score (SHS). We evaluated the fitting of the model using time-averaged DAS28 among 1000 models in which we randomly picked up one-time DAS28. We also used clinical disease activity index (CDAI) or data in the BeSt study (European population). After conditioning on autoantibody and disease duration, time-averaged DAS28 showed significant improvement of model fitting compared with one-time DAS28 in both cohorts (p = 0.001 and 0.034, respectively). Time-averaged CDAI also showed a better fit. Integration of multiple DAS fit SHS better in the BeSt study. A good fit of time-averaged DAS could be observed using five to six time points of DAS. In conclusion, time-averaged disease activity fits the joint destruction model better than one-time disease activity. Usage of time-averaged disease activity as a covariate would increase the power of studies to identify novel correlates of joint destruction.

Establishment of age- and sex-adjusted reference data for hand bone mass and investigation of hand bone loss in patients with rheumatoid arthritis treated in clinical practice: an observational study from the DANBIO registry and the Copenhagen Osteoarthritis Study.

BackgroundRheumatoid arthritis is characterised by progressive joint destruction and loss of periarticular bone mass. Hand bone loss (HBL) has therefore been proposed as an outcome measure for treatment efficacy. A definition of increased HBL adjusted for age- and sex-related bone loss is lacking. In this study, we aimed to: 1) establish reference values for normal hand bone mass (bone mineral density measured by digital x-ray radiogrammetry (DXR-BMD)); and 2) examine whether HBL is normalised in rheumatoid arthritis patients during treatment with tumour necrosis factor alpha inhibitors (TNFI).MethodsDXR-BMD was measured from hand x-rays in a reference cohort (1485 men/2541 women) without arthritis randomly selected from an urban Danish population. Sex- and age-related HBL/year was estimated. DXR-BMD was measured in rheumatoid arthritis patients (n = 350: at start of TNFI, and ~2 years after TNFI start), of which 135 patients had three x-rays (~2 years prior to TNFI, at start of TNFI, and ~2 years after TNFI start). Individual HBL/year prior to and during TNFI was calculated and compared to reference values.ResultsEstimated HBL/year varied strongly with age and sex. Compared to the reference values, 75 % of 135 patients had increased HBL prior to TNFI treatment and 59 % had increased HBL during TNFI treatment (p = 0.17, Chi-squared). In 38 % (38/101) of patients with increased HBL, HBL was normalised during TNFI treatment, whereas 47 % (16/34) of patients with normal HBL prior to TNFI had increased HBL during TNFI treatment. In the 350 patients, increased HBL during TNFI was associated with time-averaged 28-joint disease activity score (odds ratio 1.69 (95 % Confidence Interval 1.34-2.15)/unit increase, p < 0.001), and patients in time-averaged remission had lower HBL than patients without remission (0.0032 vs. 0.0058 g/cm2/year; p < 0.001, Mann-Whitney).ConclusionsWe established age- and sex-specific reference values for DXR-BMD in a large cohort without arthritis. HBL was increased in the majority of rheumatoid arthritis patients initiating TNFI in clinical practice, and only normalised in a minority during TNFI.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0952-y) contains supplementary material, which is available to authorized users.

Disease activity in rheumatoid arthritis and the risk of cardiovascular events.

Use of several immunomodulatory agents has been associated with reduced numbers of cardiovascular (CV) events in epidemiologic studies of rheumatoid arthritis (RA). However, it is unknown whether time-averaged disease activity in RA correlates with CV events. We studied patients with RA whose cases were followed in a longitudinal US-based registry. Time-averaged disease activity was assessed during followup using the area under the curve of the Clinical Disease Activity Index (CDAI), a validated measure of RA disease activity. Age, sex, presence of diabetes mellitus, hypertension, or hyperlipidemia, body mass index, family history of myocardial infarction (MI), use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), presence of CV disease, and baseline use of an immunomodulator were assessed at baseline. Cox proportional hazards regression models were examined to determine the risk of a composite CV end point that included MI, stroke, and death from CV causes. A total of 24,989 patients who had been followed up for a median of 2.7 years were included in these analyses. During followup, we observed 534 confirmed CV end points, for an incidence rate of 7.8 per 1,000 person-years (95% confidence interval [95% CI] 6.7-8.9). In models adjusted for variables noted above, a 10-point reduction in the time-averaged CDAI was associated with a 21% reduction in CV risk (95% CI 13-29). These results were robust in subgroup analyses stratified by the presence of CV disease, use of corticosteroids, use of NSAIDs or selective cyclooxygenase 2 inhibitors, and change in RA treatment, as well as when restricted to events adjudicated as definite or probable. Our findings showed that reduced time-averaged disease activity in RA is associated with fewer CV events.

Should We Redefine Treatment Targets in Rheumatoid Arthritis? Low Disease Activity Is Sufficiently Strict for Patients Who Are Anticitrullinated Protein Antibody-negative

Clinical remission currently is the treatment target for all patients with rheumatoid arthritis (RA). At the same level of inflammation, the prognosis regarding joint damage is believed to be different for anticitrullinated protein antibody (ACPA)-negative and ACPA-positive patients. Our objective was to show the difference in prognosis at similar disease activity levels, and to illustrate how this could be translated to differentiation of treatment targets. Data were used from the Nijmegen Early RA Cohort. The relation between the time-averaged disease activity level (by Disease Activity Score; DAS) and joint damage progression over 3 years was analyzed, separately for ACPA-negative and ACPA-positive patients. Joint damage was assessed as change in Ratingen score, and dichotomized as occurrence of erosions in joints that were unaffected at baseline. Linear and logistic multivariable regression models were used. The regression coefficient of DAS on change in Ratingen score was 3.9 (p < 0.001) for ACPA-negative and 4.7 (p < 0.001) for ACPA-positive patients, showing less joint damage progression at the same disease activity level in ACPA-negative patients. This difference became greater with increasing disease activity. The probability for erosions in joints unaffected at baseline was 0.35 in ACPA-negative patients when time-averaged DAS was < 2.4 versus 0.80 in ACPA-positive patients. At the same level of inflammation, ACPA-negative patients have less joint damage and lower probability for damage in newly affected joints than ACPA-positive patients. Low disease activity might be a sufficiently strict treatment target for ACPA-negative patients to prevent progression of joint damage.

Meta-analysis suggests that intensive non-biological combination therapy with step-down prednisolone (COBRA strategy) may also ‘disconnect’ disease activity and damage in rheumatoid arthritis

Background/objectiveTreatment of rheumatoid arthritis (RA) with tumour necrosis factor (TNF) antagonists changes the relationship between disease activity and progression of radiological joint damage (‘disconnect’): patients who have little or no...

Association of joint space narrowing with impairment of physical function and work ability in patients with early rheumatoid arthritis: protection beyond disease control by adalimumab plus methotrexate

ObjectivesTumour necrosis factor inhibition plus methotrexate is believed to inhibit radiographic progression independent of inflammation. This analysis assessed whether these protective effects are exerted on bone (joint erosion; JE) and/or...

The time-averaged inflammatory disease activity estimates the progression of erosions in MRI of the sacroiliac joints in ankylosing spondylitis

A method to estimate the individual ankylosing spondylitis (AS) patient radiological progression of semi-quantitative magnetic resonance imaging (MRI) changes in the sacroiliac joints has not been described yet, which this study examines. Inflammatory disease activity and MRIs of the sacroiliac joints of 38 patients with recent onset established AS were analyzed at baseline and during follow-up. Sacroiliac MRIs were semi-quantitatively assessed using a modification of the "Spondylarthritis Research Consortium of Canada" (SPARCC) method. In each patient, the annual inflammatory disease activity was estimated by the time-averaged C-reactive protein (CRP; mg/l), calculated as the area under the curve. The mean (SD) CRP decreased from 1.3 (1.8) at baseline to 0.5 (0.6) at follow-up MRI (p < 0.04), which has been performed after a mean (SD) disease course of 2.8 (1.5) years. The mean (SD) annual increase (∆) of SPARCC score from baseline to follow-up MRI was 0.4 (0.4). Baseline individual SPARCC sub-score for bone marrow edema did not statistically significantly correlate with individual ∆SPARCC sub-score for erosions (p = N.S.). The individual AS patient correlation between annual time-averaged inflammatory disease activity and each annual ∆SPARCC sub-scores was only statistically significant for erosions (p < 0.01; r = 0.71). Our results show that bone marrow edema and contrast-medium enhancement at baseline do not relate to the progression of erosions but the calculation of the individual patient annual time-averaged inflammatory disease activity allows to estimate the annual progression of erosions in sacroiliac MRIs of patients with AS.

Influence of variations across the MMP-1 and -3 genes on the serum levels of MMP-1 and -3 and disease activity in rheumatoid arthritis

Matrix metalloproteinases (MMPs) are involved in joint destruction in rheumatoid arthritis (RA), and are strongly associated with levels of inflammation. To understand the relationship between MMP-1 and -3 variants and MMP levels in RA, we investigated the genotypic and haplotypic relationships of the MMP-1 and -3 genes with circulating levels of these MMPs. The genotypes of single-nucleotide polymorphisms (SNPs) rs1799750 (1G/2G, MMP-1 promoter), rs495366 (G/A, intergene), rs679620 (A/G, MMP-3 coding region) and rs3025058 (5A/6A, MMP-3 promoter) were determined in 430 RA patients. Each polymorphism was associated with serum levels of MMP-1 (P trend <0.0001 for each SNP), with haplotype 1G-G-A-5A associated with the highest level. The intergenic and MMP-3 SNPs were associated with MMP-1 levels independent of the MMP-1 promoter SNP. The MMP-3 SNPs were associated with serum MMP-3 level (P trend <0.0001 for each SNP), and were each associated with mean time-averaged disease activity (DAS28) in patients followed up for 2 years (P=0.003). Our findings indicate that several closely linked polymorphisms in the MMP-1-MMP-3 loci have an important role in determining the circulating levels of these MMPs in RA, and that MMP-3 polymorphism is associated with the level of disease activity over time.

Disease activity as a risk factor for myocardial infarction in rheumatoid arthritis

Objective:Patients with rheumatoid arthritis (RA) are at greater risk of developing coronary heart disease than the general population. Systemic inflammation may contribute to this risk. This study investigated whether the...

Disconnect between inflammation and joint destruction after treatment with etanercept plus methotrexate: Results from the trial of etanercept and methotrexate with radiographic and patient outcomes

To determine the relationship between disease activity and radiographic progression of joint destruction in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), those treated with etanercept, and those treated with the combination of MTX plus etanercept. Baseline, 12-month, and 24-month data from the Trial of Etanercept and Methotrexate with Radiographic and Patient Outcomes database were analyzed. The dependent variable was the 1-year change in the modified Sharp/van der Heijde score (Sharp score); therefore, 2 interval changes per patient were available. Interval change in the Sharp score was modeled by time (years), treatment, disease activity, and the interaction (disease activity x treatment). Disease activity was reflected by the time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive protein (taCRP) level, which were calculated per 1-year interval. Generalized mixed linear modeling (GMLM) was used to adjust for within-patient correlation. GMLM confirmed a significant interaction between treatment and the taCRP level and taDAS with respect to the change in Sharp score (P = 0.012 and P = 0.03, respectively). In patients treated with MTX alone, radiographic progression increased with an increasing taCRP level or taDAS, although progression rates were low in patients whose disease was in remission and in those with low-to-moderate disease activity. This relationship was less clear in patients treated with etanercept and was absent in those who received combination therapy. Combination therapy with MTX plus etanercept uncouples the classic relationship between disease activity and radiographic progression in patients with RA.