Association of a multibiomarker disease activity score at multiple time-points with radiographic progression in rheumatoid arthritis: results from the SWEFOT trial.
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ABSTRACT:
SUBMITTER: Hambardzumyan K
PROVIDER: S-EPMC4780313 | biostudies-other | 2016
REPOSITORIES: biostudies-other
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Project description:Demonstrating inhibition of the structural damage to joints as a statistically significant difference in radiographic progression as measured by the van der Heijde modified Total Sharp Score (mTSS) is a common objective in trials for rheumatoid arthritis treatments. The frequently used analysis of the covariance model with missing data imputed using linear extrapolation (analyses of covariance, ANCOVA+LE) may not be ideal for long-term extension studies or for paediatric studies. The random coefficient (RC) model may represent a better alternative.A two-arm (active treatment and placebo) setting with a week 44 study period was considered. RC model, ANCOVA+LE and ANCOVA with last observation carried forward imputation were compared under different scenarios in bias, root mean square error (RMSE), power and type I error rate.The RC model outperformed ANCOVA+LE in metrics measuring bias, RMSE, power and type I error rate under the evaluated scenarios. ANCOVA and RC provide similar performance when there are no missing data. With missing data, RC+observed (OBS) provides similar or better results than ANCOVA+LE in power and bias.Our simulations support that RC is both a more sensitive and a more precise alternative to the commonly used ANCOVA+LE as a primary method for analysing mTSS in long-term extension and paediatric studies with a higher likelihood of missing data. The RC model can provide a reference at time points with missing data by estimating a slope; mTSS change by one unit change in time. ANCOVA+LE is recommended as a sensitivity analysis.
| S-EPMC10083852 | biostudies-literature
Project description:ObjectivesTo study clinical predictors for radiographic progression after 1 year in an early rheumatoid arthritis (RA) trial.MethodsIn the SWEFOT trial population, disease modifying antirheumatic drug (DMARD) naïve RA patients started methotrexate; 3-month responders (DAS28 <3.2) continued (n=147), while non-responders were randomised to addition of sulfasalazine+hydroxychloroquine (n=130) or infliximab (n=128). X-rays were scored by the Sharp-van der Hejde score (SHS) method and radiographic progression was defined as a ≥5 increase after 1 year. Potential baseline predictors of radiographic progression were tested using multivariable logistic regression, adjusted for potential confounders.Results79 of 311 patients with available radiographs at baseline and follow-up had radiographic progression. The following baseline parameters were independent predictors of radiographic progression at 1 year: baseline erosions (adjusted OR=2.29, 95% CI 1.24 to 4.24), erythrocyte sedimentation rate (adjusted OR per tertile increase=1.72, 95% CI 1.12 to 2.65) and C-reactive protein (adjusted OR per tertile increase=1.52, 95% CI 1.03 to 2.26). Current smoking was an independent predictor of radiographic progression (adjusted OR=2.17, 95% CI 1.06 to 4.45). These results remained after further adjustment for treatment strategy. Three-dimensional matrix including current smoking status, erosions and C-reactive protein tertiles showed a 12-63% risk gradient from patients carrying none compared with all predictors. Rheumatoid factor (RF)/anti-cyclic citrullinated peptide (anti-CCP) positivity did not significantly predict radiographic progression using SHS increase ≥5 as cut-off. In a secondary exploratory analysis using cut-off >1, both RF and anti-CCP positivity were significant predictors in the unadjusted, but not the adjusted analyses. The other parameters also remained significant using this lower cut-off.ConclusionsIn addition to previously described predictors, we identified smoking as a strong independent risk factor for radiographic progression in early RA.Trial registration numberNCT00764725.
| S-EPMC4515990 | biostudies-literature
Project description:Background and objectivesPreclinical interstitial lung disease (pILD) may represent the early stages of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the characteristics, clinical outcomes, and risk factors associated with fibrosis progression in RA-ILD, including pILD and ILD, remain poorly understood.MethodsBaseline data were compared between patients with RA-ILD and those with RA alone. Multivariate logistic regression and Cox regression analyses were performed to identify risk factors associated with the prevalence and imaging progression of RA-ILD, respectively.ResultsAmong the 371 enrolled RA patients, 32.3% had RA-ILD. Multiple logistic regression analyses identified age over 60.0 years (OR 2.22), smoking (OR 2.09), diabetes mellitus (DM) (OR 3.09), mixed connective tissue disease (MCTD) (OR 2.98), serum lactate dehydrogenase (LDH) levels exceeding 250.0 U/L (OR 6.73), and positive anti-cyclic citrullinated peptide (anti-CCP) antibody (OR 2.06) as independent risk factors for RA-ILD (p< 0.05 or 0.01). Among the 98 RA-ILD patients who underwent follow-up for a median duration of 19.1 months, 51.0% demonstrated fibrotic progression on high-resolution computed tomography (HRCT). Multiple Cox regression analysis identified DM (HR 2.03), Disease Activity Score in 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR) greater than 5.1 (HR 2.21), and baseline HRCT scores exceeding 5.0 (HR 2.30) as independent risk factors for fibrosis progression in RA-ILD (p< 0.05 or 0.01).ConclusionNearly one-third of RA patients in this cohort had prevalent pILD or ILD, and half of them demonstrated imaging progression during follow-up. DM, higher DAS28-ESR, and advanced HRCT scores were identified as independent risk factors for progressive fibrosis in RA-ILD.
| S-EPMC10556458 | biostudies-literature
Project description:BackgroundThe multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors.MethodsFour cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N = 953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (ΔTSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression.ResultsUnivariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (ΔTSS > 5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (ΔTSS > 5) increased from < 2% in the low (1-29) adjusted MBDA category to 16% in the high (45-100) category. A modeled risk curve indicated that risk increased continuously, exceeding 40% for the highest adjusted MBDA scores.ConclusionThe adjusted MBDA score was validated as an RA disease activity measure that is prognostic for radiographic progression. The adjusted MBDA score was a stronger predictor of radiographic progression than conventional risk factors, including seropositivity, and its prognostic ability was not significantly improved by the addition of DAS28-CRP, CRP, SJC, or CDAI.
| S-EPMC7784276 | biostudies-literature
Project description:IntroductionEtanercept (ETN) has been shown to slow radiographic progression of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical trials. This real-world, non-interventional study assessed radiographic progression in patients with RA or PsA treated with ETN for ≤ 36 months in outpatient care in Germany (NCT01623752).MethodsPatients with RA or PsA attended ≤ 10 visits across two study phases (phase 1: seven visits, baseline to month 18; phase 2: three visits until month 36). Radiographs were taken at baseline (Rx1), months 12-18 (Rx2), and/or months 30-36 (Rx3). Historic radiographs (Rx0) taken 12-48 months pre-baseline were also evaluated (if available). The primary endpoint was the change in modified total Sharp score (mTSS). The erosion score (ES) and joint space narrowing score (JSN) were also evaluated.ResultsOverall, 1821 patients were enrolled (RA: n = 1378; PsA: n = 440). In patients with Rx1 and Rx2 (RA: n = 511; PsA: n = 167), the mean mTSS remained stable for both disease groups, and the annualized median change in mTSS was 0. In patients with Rx0, Rx1, and Rx2 (RA: n = 180; PsA: n = 47), annualized radiographic progression in mTSS, ES, and JSN was larger in the pre-ETN treatment phase than during ETN treatment in both disease groups. The percentage of patients with radiographic non-progression was higher during ETN treatment versus pre-ETN. Improvement in clinical disease activity and patient-reported outcomes was also observed.ConclusionsThis was the first real-world, non-interventional study to report systematically collected radiographic data in a large cohort of patients with RA or PsA under treatment with a biologic. In patients with available radiographic data, mean radiographic progression was lower and the proportion of patients without progression was greater during ETN treatment than in the pre-ETN period.
| S-EPMC9931988 | biostudies-literature
Project description:Prediction of radiographic progression (RP) in early rheumatoid arthritis (eRA) would be very useful for optimal choice among available therapies. We evaluated a multi-biomarker disease activity (MBDA) score, based on 12 serum biomarkers as a baseline predictor for 1-year RP in eRA.Baseline disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), disease activity score based on C-reactive protein (DAS28-CRP), CRP, MBDA scores and DAS28-ESR at 3?months were analysed for 235 patients with eRA from the Swedish Farmacotherapy (SWEFOT) clinical trial. RP was defined as an increase in the Van der Heijde-modified Sharp score by more than five points over 1?year. Associations between baseline disease activity measures, the MBDA score, and 1-year RP were evaluated using univariate and multivariate logistic regression, adjusted for potential confounders.Among 235 patients with eRA, 5 had low and 29 moderate MBDA scores at baseline. None of the former and only one of the latter group (3.4%) had RP during 1?year, while the proportion of patients with RP among those with high MBDA score was 20.9% (p=0.021). Among patients with low/moderate CRP, moderate DAS28-CRP or moderate DAS28-ESR at baseline, progression occurred in 14%, 15%, 14% and 15%, respectively. MBDA score was an independent predictor of RP as a continuous (OR=1.05, 95% CI 1.02 to 1.08) and dichotomised variable (high versus low/moderate, OR=3.86, 95% CI 1.04 to 14.26).In patients with eRA, the MBDA score at baseline was a strong independent predictor of 1-year RP. These results suggest that when choosing initial treatment in eRA the MBDA test may be clinically useful to identify a subgroup of patients at low risk of RP.WHO database at the Karolinska Institute: CT20080004; and clinicaltrials.gov: NCT00764725.
| S-EPMC4431327 | biostudies-literature
Project description:To evaluate the multi-biomarker disease activity (MBDA) score as a predictor of radiographic progression and compare it with other risk factors among patients with established RA receiving non-biologic DMARDs.For 163 patients with RA, we assessed 271 visits for MBDA score (scale of 1-100), clinical data and subsequent 1-year radiographic progression (change in Sharp-van der Heijde score [SHS]). Scatter plot and non-parametric quantile regression curves evaluated the relationship between the MBDA score and change in SHS. Changes in joint space narrowing and erosions were compared among MBDA categories with Wilcoxon rank-sum tests. The ability of the MBDA score to independently predict progression was determined by multivariate models and cross-classification of MBDA score with other risk factors. Generalized estimating equation methodology was used in model estimations to adjust for same-patient visits, always ?1 year apart.Patient characteristics included 67% female, 66%/67% RF(+)/anti-CCP(+); mean age 55 years, MBDA score 43 (moderate = 30-44); median disease duration 4.6 years, SHS 23. Radiographic progression was infrequent for low MBDA scores. Relative risk for progression increased continuously as the MBDA score increased, reaching 17.4 for change in SHS >5 with MBDA scores ?60. Joint space narrowing and erosion progression were associated with MBDA score. MBDA score was associated with radiographic progression after adjustments for other risk factors. MBDA score significantly differentiated risk for progression when swollen joint count, CRP or DAS28-CRP was low, and among seropositive patients.MBDA score enhanced the ability of conventional risk factors to predict radiographic progression in patients with established RA receiving non-biologic DMARDs.
| S-EPMC4710803 | biostudies-other
Project description:ObjectivesTo determine whether molecular remission defined by a multi-biomarker disease activity (MBDA) score predicts a reduced risk of joint damage progression, and whether the MBDA score can augment existing classifications of remission.MethodsThe study examined 271 visits for 163 RA patients in the Leiden Early Arthritis Cohort. The MBDA score and other variables from each visit were evaluated for prediction of progression [change in Sharp-van der Heijde Score (?SHS) >3] over the ensuing 12 months. Positive likelihood ratios (PLRs) for non-progression were calculated for remission based upon DAS based on 28-joint counts and CRP (DAS28-CRP <2.32), EULAR/ACR Boolean criteria and MBDA score (?25).ResultsNinety-three per cent of patients in MBDA-defined remission did not experience progression, compared with 70% of patients not in MBDA remission (P = 0.001). There were no significant differences in the fraction of non-progressers between patients in remission and those not in remission using either DAS28-CRP or EULAR/ACR criteria. The PLR for non-progression over 12 months for MBDA remission was 4.73 (95% CI 1.67, 15.0). Among patients in DAS28-CRP remission, those with a high MBDA score were 2.3 times as likely (95% CI 1.1, 3.7) to have joint damage progression during the next year.ConclusionMBDA-defined remission was an indicator of limited radiographic progression over the following 12 months. For patients in DAS28-CRP remission, high MBDA scores were a significant indicator of elevated risk of progression. MBDA results may provide a useful adjunct to clinical assessment to identify progression-free remission and assess subclinical disease.
| S-EPMC3630394 | biostudies-literature
Project description:BackgroundAdipokines have inflammatory and immunomodulatory properties that may contribute to erosive joint damage. The association of serum adipokine levels with progression of radiographic joint damage in patients with rheumatoid arthritis (RA) was prospectively explored.MethodsPatients with RA underwent serum adipokine assessment (adiponectin, resistin, leptin) at three timepoints and hand/feet x-rays, scored using the Sharp-van der Heijde Score (SHS), at baseline and the third study visit, separated by an average of 39±4 months. The associations of baseline and average adipokine levels with change in SHS were explored, adjusting for pertinent confounders.ResultsOf the 152 patients studied, 85 (56%) showed an increase in SHS (defined as >0 SHS units). Among the adipokines studied, only adiponectin was significantly associated with radiographic progression, with average adiponectin levels more strongly associated than baseline levels. After adjusting for average C reactive protein and baseline SHS, patients in the highest quartile of average adiponectin had a SHS progression rate more than double the lowest quartile (1.00 vs 0.48 units/year; p=0.008). Similarly, those in the highest quartile of adiponectin had a more than fivefold greater odds of any radiographic progression compared with the lowest quartile (OR 5.75; p=0.002). The magnitude of the association of average adiponectin levels with radiographic progression was greater in women, those with body mass index <30 kg/m(2) and those receiving baseline biological disease-modifying antirheumatic drugs.ConclusionsThese prospective data provide evidence of temporality and dose-response in the relationship between circulating adiponectin and erosive joint destruction in RA, and highlight subgroups of patients at highest risk for adiponectin-associated radiographic progression.
| S-EPMC3543946 | biostudies-literature
Project description:INTRODUCTION: Adipokines such as adiponectin, leptin, and visfatin/nicotinamide phosphoribosyltransferase (NAMPT) have recently emerged as pro-inflammatory mediators involved in the pathophysiology of rheumatoid arthritis (RA). We aimed to determine whether serum adipokine levels independently predicted early radiographic disease progression in early RA. METHODS: In total, 791 patients were included from the prospective Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort who met the American College of Rheumatology-European League Against Rheumatism criteria for RA (n?=?632) or had undifferentiated arthritis (UA) (n?=?159). Enzyme-linked immunosorbent assay (ELISA) was used to assess baseline serum levels of adiponectin, leptin, and visfatin/NAMPT. In the RA group, we tested the association of serum adipokine levels and (a) baseline radiographic damage and (b) radiographic disease progression, defined as a change >0 or ? 5 in total Sharp-van der Heijde Score (?SHS) between inclusion and 1 year (?SHS ?1 or rapid radiographic progression: ?SHS ?5), adjusting for confounders (age, sex, body-mass index, insulin resistance, C-reactive protein level, Disease Activity Score in 28 joints, Health Assessment Questionnaire score, autoantibody status, steroid use, and radiographic evidence of RA damage at inclusion). RESULTS: Adiponectin level was independently associated with baseline total SHS (adjusted ??=?0.12; P?=?0.006). It was also associated with ?SHS ?1 (adjusted odds ratio (aOR)?=?1.84 (1.25 to 2.72)) involving erosive as well as narrowing disease progression (aOR?=?1.73 (1.17 to 2.55) and 1.93 (1.04 to 3.57), respectively). Serum adiponectin level predicted ?SHS ?5 (aOR?=?2.0 (1.14 to 3.52)). Serum leptin level was independently associated only with ?SHS >0 (aOR?=?1.59 (1.05 to 2.42)). Conversely, serum visfatin/NAMPT level and radiographic disease progression were unrelated. Considering the receiver-operated characteristic curves, the best adiponectin cut-offs were 4.14 ?g/ml for ?SHS ?1 and 6.04 ?g/ml for ?SHS ?5, with a good specificity (58% and 75% for ?SHS ?1 and ?SHS ?5, respectively) and high negative predictive values (75% and 92% for ?SHS ?1 or ?SHS ?5, respectively). CONCLUSION: Serum adiponectin level is a simple useful biomarker associated with early radiographic disease progression in early RA, independent of RA-confounding factors and metabolic status.
| S-EPMC3978925 | biostudies-literature