Independent Predictor Of Radiographic Progression Research Articles

Serum 14-3-3η as predictor of clinical remission and progression of structural damage in early rheumatoid arthritis following a treat-to-target strategy in a randomized controlled trial

Objective 14-3-3η is a proinflammatory mediator critical to joint destruction in rheumatoid arthritis (RA). We aimed to evaluate serum 14-3-3η for predicting disease activity and radiographic progression in patients with early RA in the double-blinded, randomized OPERA trial. Method 180 patients with early RA were randomized to receive methotrexate (MTX) + adalimumab or MTX + placebo in combination with glucocorticoid injections into swollen joints. Disease activity was measured using the 28-joint Disease Activity Score–C-reactive protein (DAS28-CRP). Clinical remission was defined as DAS28-CRP < 2.6. X-rays of hands and feet were evaluated by the Total Sharp van der Heijde score (TSS). Radiographic progression was defined as exceeding the smallest detectable change (1.8 TSS-units). Serum 14-3-3η was determined by enzyme-linked immunosorbent assay. Multivariate logistic regression models were used to identify predictors of DAS28-CRP remission at 6 months and radiographic progression at 12 months. Results Baseline 14-3-3η was a borderline significant independent predictor of radiographic progression at 12 months (odds radio = 1.02, 95% confidence interval 1.00–1.03, p = 0.05). In anti-cyclic citrullinated peptide antibody (ACPA)-negative patients, a moderate/high baseline 14-3-3η concentration increased the risk of radiographic progression at 12 months [4/51 (8%) vs 3/9 (33%), χ2 = 4.823, p = 0.028]. No value of 14-3-3η for predicting achievement of clinical remission was found. Conclusion Serum 14-3-3η was a borderline significant predictor of radiographic progression, particularly in ACPA-negative patients, but not of predicting achievement of clinical remission. Optimal cut-off levels of 14-3-3η for predicting radiographic progression in RA need further clarification.

Can whole spine magnetic resonance imaging predict radiographic progression and inflammatory activity in axial spondyloarthritis?

To investigate whether initial whole spine magnetic resonance imaging (MRI) predicts radiographic progression and inflammatory activity in patients with axial spondyloarthritis (axSpA). A retrospective analysis of spine MRI and X-rays from 70 axSpA patients was conducted. The number of affected discovertebral units was determined according to the definition of pathologic lesions on spine MRI set down by the ASAS/OMERACT group. Radiographic progression was defined as an increase in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) of≥2 compared with baseline. The association of spine MRI with radiographic progression, cumulative C-reactive protein (CRP), and cumulative erythrocyte sedimentation rate (ESR) was investigated. The axSpA-relevant lesions on spine MRI at baseline were independent predictors of radiographic progression. Arthritis of the costovertebral and costotransverse joints on MRI showed the highest odds ratio at 3years (OR [95% CI]: 2.54 [1.29-5.02]). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) for radiographic progression at 2years was 0.89 [95% CI: 0.81-0.96] for structural lesions and 0.83 [95% CI: 0.72-0.94] for inflammatory lesions. Notably, subgroup analysis of 26 patients with mSASSS=0 showed that fatty metaplasia on MRI were highly predictive of radiographic progression at 3years (AUC [95% CI]: 0.87 [0.61-1.00]). Moreover, 3-year cumulative ESR and CRP values increased in proportion to the extent of inflammatory lesions on initial MRI. Initial MRI assessment of the whole spine may predict radiographic progression and subsequent systemic inflammatory burden in axSpA patients, particularly those without axSpA-relevant abnormalities on spine X-rays.

Predictors of radiographic progression for NTM-pulmonary disease diagnosed by bronchoscopy.

A single isolate of nontuberculous mycobacterium (NTM) from bronchoscopic samples satisfies the microbiological criterion for diagnosing NTM-pulmonary disease (PD). Studies investigating patients with NTM-PD and multiple culture-negative sputum samples but culture-positive bronchoscopic samples are lacking. We investigated the clinical characteristics, outcome, and predictors of radiographic progression in this special population. Patients with negative NTM culture from ≥2 expectorated sputum samples within the 3 months prior to bronchoscopy diagnosis of NTM-PD between 2009 and 2017 were included. Patient characteristics and clinical course were described. Predictors for radiographic progression of NTM-PD within 2 years were analysed by using multivariate logistic regression. Among 66 patients with bronchoscopy-diagnosed NTM-PD, radiographic progression occurred within 2 years in 17 (26%). Of the 60 patients not initially treated, radiographic progression occurred in 17 (28%). Among them, 10 never received treatment, with 6 deteriorating and 3 dying. Of the 6 and 7 patients who received treatment immediately after NTM-PD diagnosis and after radiographic progression, respectively, none had further radiographic progression. The independent predictors of radiographic progression were male sex, body mass index <18.5kg/m2, use of inhaled corticosteroids, and acid-fast smear grade ≥2 of index bronchoscopic samples. Among patients with bronchoscopy-diagnosed NTM-PD, one fourth experienced radiographic progression within 2 years. The risk was even higher in those with the aforementioned predictors, immediate treatment or close monitoring is recommended. For others, conservative management by regular microbiological monitoring for sputum samples and image follow-up may be the optimal choice.

Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis

BackgroundThe objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA).MethodsThis was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression.ResultsData from 109 patients with a mean RA duration of 0.7 years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p < 0.01); changes in RAMRIQ synovitis and osteitis at months 1 and 3 were significant predictors of RAMRIS erosions and radiographic progression at month 12 (all p < 0.01). In subsequent multivariate analyses, RAMRIS erosion change at month 1 (p < 0.05) and RAMRIQ osteitis changes at months 1 and 3 (both p < 0.01) were significant independent predictors of radiographic progression at month 12. Univariate analyses demonstrated that changes in Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) at months 1 and 3 were not predictive of month 12 radiographic progression.ConclusionsMRI changes seen as early as 1 month after RA treatment initiation have the potential to better predict long-term radiographic progression than changes in disease activity measures.Trial registrationClinicalTrials.gov, NCT01164579.

Interleukin-34 Promotes Fibrocyte Proliferation.

Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting multiple joints. It remains unclear which factors in the circulation are associated with the systemic spread of the disease. Fibrocytes are pluripotent mesenchymal stem cells present in the circulation of RA patients. Our earlier findings implicated activated fibrocytes in the etiology of onset and pathogenesis of RA. Elevated levels of interleukin-34 (IL-34) in the serum and synovial fluid of RA patients are associated with rheumatoid factor and anticyclic citrullinated peptide antibodies, indicators of RA. Moreover, IL-34 levels are independent predictors of radiographic progression in RA patients. We provide evidence of simultaneous elevated levels of IL-34 and increased numbers of activated fibrocytes in the circulation of mice induced to develop arthritis. In vitro, IL-34 treatment induced the proliferation of fibrocytes, mediated by activation of cognate CSF-R1s on fibrocytes. Taken together, we infer that IL-34 has a role in stimulating fibrocyte proliferation and activation during arthritis, thereby contributing to both onset of RA and systemic spread of disease.

Baseline MRI bone erosion predicts the subsequent radiographic progression in early rheumatoid arthritis patients who achieved sustained good clinical response

Objective: To examine whether magnetic resonance imaging (MRI) findings at baseline predict radiographic progression in early-stage rheumatoid arthritis (RA) patients who have achieved sustained good clinical response.Methods: This is a sub-analysis from the one-year observational study of Nagasaki University Early Arthritis Cohort. Definition of ‘good clinical response’ was a decrement of disease activity score (DAS) 28 ≧ 1.2 at three months with achievement of DAS28 remission through 6–12 months. Gd-enhanced MRI of both wrists and finger joints were examined at baseline and scored using rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Annual increment of Genant-modified Sharp score (GSS) > 0 was defined as ‘radiographic progression’. Predictors of radiographic progression were determined by logistic regression analysis.Results: Twenty-four subjects were selected in the present study. Each median RAMRIS synovitis, bone edema, bone erosion, and GSS at baseline were 6.5, 0.5, 0, and 0, respectively. Five patients developed radiographic progression at one year. Multivariate logistic regression analysis has shown that RAMRIS bone erosion at baseline is the only independent predictor of radiographic progression at one year (p = .032).Conclusions: Our data suggest that MRI bone erosion predicts poor radiographic outcome of early-stage RA even if it has been successfully treated.

SAT0041 14-3-3Eta Predicts Radiographic Progression in Recent-Onset Polyarthritis Patients

BackgroundEarly RA diagnosis and timely treatment can improve patient outcomes. Markers are needed to identify patients with early disease who are at high-risk of joint damage progression. Current clinical and...

Pretreatment multi-biomarker disease activity score and radiographic progression in early RA: results from the SWEFOT trial.

ObjectivesPrediction 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.MethodsBaseline 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.ResultsAmong 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).ConclusionsIn 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.Trial registration numberWHO database at the Karolinska Institute: CT20080004; and clinicaltrials.gov: NCT00764725.

Current smoking status is a strong predictor of radiographic progression in early rheumatoid arthritis: results from the SWEFOT trial

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...

Skin pentosidine in very early hip/knee osteoarthritis (CHECK) is not a strong independent predictor of radiographic progression over 5 years follow-up

Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA. The 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed. Both pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R(2) = 0.60-0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R(2) = 0.07-0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis. Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline.

Skin pentosidine in very early hip/knee osteoarthritis (CHECK) is not a strong independent predictor of radiographic progression over 5 years follow-up

Purpose: Age-related changes in articular cartilage are likely to play a role in the aetiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced-glycation-endproducts (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA. Methods: The Cohort Hip and Cohort Knee (CHECK) is a cohort of participants with very early OA. In this study data of 5 years follow-up were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (K&L and Altman scores). Radiographic OA burden was expressed as the summed K&L grade or Altman scores of both hips and knees. Radiographic OA progression was expressed as the area under the curve (AUC) of the summed K&L grade over the 5 years minus the baseline value over 5 years. The burden of radiographic joint damage was expressed as the AUC over 5 years. For the summed Altman scores for JSN and osteophyte formation the same approaches were used to determine progression and burden scores per patient. Baseline skin pentosidine levels (and urinary CTXII as a comparator) were measured by HPLC (and ELISA). Univariate and multivariate associations including baseline radiographic damage, age, gender, BMI and kidney function were performed. Results: Of 183 participants all data were available. At 5-year follow-up radiographic progression of OA was seen (sum K&L score 1.69 ± 1.13 at T0 versus 3.30 ± 1.81 at T5). Both pentosidine and uCTXII correlated with this radiographic progression and burden (ie progression AUC sum K&L score R=0.167 p=0.024 and R=0.323 and p=0.000 for skin pentosidine and urine CTXII, respectively). In multivariate analysis, in general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R2=0.60-0.88), but this was predominantly determined by baseline radiographic damage (without this parameter R2=0.07-0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariate analysis. Conclusion: Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better than uCTXII in predicting radiographic progression or burden. Burden of damage over 5 year is mainly determined by radiographic joint damage at baseline. This study was supported by the Dutch Arthritis Association.

Baseline serum MMP-3 levels in patients with Rheumatoid Arthritis are still independently predictive of radiographic progression in a longitudinal observational cohort at 8 years follow up

IntroductionAt present, there is no reliable tool for predicting disease outcome in patients with rheumatoid arthritis (RA). We previously demonstrated an association between specific baseline biomarkers/clinical measures including matrix metalloproteinase-3 (MMP-3) and 2-year radiographic progression in patients with RA. This study further evaluates the predictive capability of these baseline variables with outcome extended over 8-years.MethodsFifty-eight of the original cohort (n = 118) had radiographic progression from baseline to mean 8.2-years determined using the van der Heijde modified Sharp method. The contribution of each predictor variable towards radiographic progression was assessed with univariate and multivariate analyses.ResultsTraditional factors (including erythrocyte sedimentation rate, C-reactive protein, anti-cyclic citrullinated peptide (anti-CCP), and rheumatoid factor) and biomarkers of tissue destruction (including MMP-3, C-telopeptide of type II collagen, cartilage oligomeric matrix protein, and tissue inhibitor of metalloproteinase 1) measured at baseline were associated with radiographic progression at endpoint. Multivariate logistic regression identified anti-CCP seropositivity [OR 9.29, 95%CI: 2.29-37.64], baseline elevated MMP-3 [OR 8.25, 95%CI: 2.54-26.78] and baseline radiographic damage [OR 5.83, 95%CI: 1.88-18.10] as the strongest independent predictors of radiographic progression. A model incorporating these variables had a predictive accuracy of 0.87, assessed using the area under the receiver operating characteristic curve.ConclusionIn our cohort with onset of RA symptoms < 2-years, multivariate analysis identified anti-CCP status and baseline MMP-3 as the strongest independent predictors of radiographic disease outcome at 8.2-years. This finding suggests determination of baseline MMP-3, in conjunction with traditional serologic markers, may provide additional prognostic information for patients with RA. Furthermore, these findings highlight the importance of continued research into a broad range of biomarkers as potential predictors of joint damage.

Risk factors for radiographic progression in psoriatic arthritis: subanalysis of the randomized controlled trial ADEPT

IntroductionTo identify independent predictors of radiographic progression in psoriatic arthritis (PsA) for patients treated with adalimumab or placebo in the Adalimumab Effectiveness in PsA Trial (ADEPT).MethodsUnivariate analyses and multivariate linear regression analyses assessed risk for radiographic progression (change in modified total Sharp score, ΔmTSS > 0.5) from baseline to week 24 for C-reactive protein (CRP) and other baseline variables, and for 24-week time-averaged CRP (univariate analysis only). Subanalyses determined mean ΔmTSS for CRP subgroups. Analyses were post hoc, with observed data.ResultsOne hundred and forty-four adalimumab-treated patients and 152 placebo-treated patients were assessed. Mean CRP was 64% lower by week 2 with adalimumab and essentially unchanged with placebo. Univariate analyses indicated that elevated CRP at baseline and time-averaged CRP were strongly associated with radiographic progression for placebo-treated patients but not for adalimumab-treated patients. Multivariate analysis confirmed that elevated baseline CRP was the only strong independent risk factor for radiographic progression (for CRP ≥1.0 mg/dl: odds ratio = 3.28, 95% confidence interval = 1.66 to 6.51, P < 0.001). Adalimumab treatment reduced risk of progression approximately fivefold. The difference between mean ΔmTSS for adalimumab versus placebo was greatest for patients with baseline CRP ≥2.0 mg/dl (-0.5 vs. 2.6).ConclusionsSystemic inflammation in PsA, as indicated by elevated baseline CRP, was the only strong independent predictor of radiographic progression. This association was observed predominantly for placebo-treated patients. Adalimumab treatment substantially reduced the overall risk of radiographic progression, and provided greatest radiographic benefit for patients with the greatest CRP concentrations at baseline.Trial RegistrationTrial registration: NCT00195689.

MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2-year randomised controlled trial (CIMESTRA)

Objective:To identify predictors of radiographic progression in a 2-year randomised, double-blind, clinical study (CIMESTRA) of patients with early rheumatoid arthritis (RA).Methods:Patients with early RA (n = 130) were treated with...

Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis

In prospective studies, only baseline radiographic damage has been identified as an independent predictor of radiographic progression in ankylosing spondylitis (AS). Several biomarkers have been identified as independent predictors of radiographic progression in rheumatoid arthritis, however, and these may be of use in AS. This study was undertaken to analyze serologic biomarkers as predictors of radiographic progression in AS. We measured a panel of biomarkers reflecting cartilage turnover and osteoclasis. These biomarkers were cartilage oligomeric matrix protein, human cartilage gp-39 (YKL-40), type II collagen epitopes detected by the C2C and C1,2C degradation assays and the CPII synthesis assay, aggrecan 846 epitope, osteoprotegerin, and matrix metalloproteinase 3 (MMP-3). The analysis was performed in a cohort of AS patients from the Netherlands, Belgium, and France enrolled in a longitudinal study, the Outcome Assessments in Ankylosing Spondylitis International Study. We examined 2-year radiographic progression data scored using the modified Stoke AS Spine Score (mSASSS). Complete data were available on 97 patients. Only the biomarkers YKL-40 and MMP-3 showed weak to moderate univariate correlation with 2-year progression. After adjustment for sex, age, disease duration, C-reactive protein level, and baseline mSASSS, only MMP-3 was significantly associated with 2-year progression (beta = 0.29, P = 0.004). Logistic regression analysis revealed MMP-3 (cutoff 68 ng/ml; odds ratio 9.4 [95% confidence interval 1.6-56]) and baseline mSASSS (cutoff 10 mSASSS units; odds ratio 18.6 [95% confidence interval 2.5-138]) as the only independent predictors of 2-year progression (cutoff 3 mSASSS units; model R(2) = 50%). MMP-3 was primarily contributory in patients who already had substantial baseline damage (>10 mSASSS units). These results indicate that MMP-3 is a significant independent predictor of radiographic progression in patients with AS, particularly in those with preexisting radiographic damage.

High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study

Objectives:New effective therapies with particularly good effect on joint destruction have highlighted the need for reliable predictors of radiographic progression in rheumatoid arthritis (RA). Our objective was to assess the...

Radiographic outcome of recent-onset rheumatoid arthritis: a 19-year study of radiographic progression.

To describe the longitudinal radiographic course of rheumatoid arthritis (RA), and to identify and quantitate predictors of radiographic progression. This prospective, longitudinal study of radiographic progression and clinical predictors of RA involved 256 patients with RA who were seen within the first 2 years of disease (mean 0.77 years) and were followed up for up to 19 years. Participants underwent a total of 6,278 clinical assessments (mean 24.5) and 934 paired radiographs (mean 3.1, range 2-6). Clinical assessments at every visit included determination of the erythrocyte sedimentation rate (ESR), grip strength, pain scores, tender joint counts, and anxiety and depression measurements. Regression analyses utilized time-integrated predictors. Overall, radiographic progression rates, as measured by the summary Sharp scores, appeared constant over the course of RA. The strongest correlate of progression was the time-integrated ESR (rho=0.53). This association grew stronger with time. At 0-5 years, 5-10 years, 10-15 years, and 15-20 years, correlations were 0.40, 0.50, 0.65, and 0.74, respectively, and for the period 10-20 years, the correlation was 0.67. In multivariate models, the mean ESR, mean grip strength, rheumatoid factor positivity, and tender joint count were independent predictors of radiographic progression. Radiographic damage occurs at a constant rate in RA, and is not greater early in RA or reduced later in the course of the illness. Acute-phase reactants are, by far, the strongest determinants of progression.