Progression Of Radiographic Damage Research Articles

Erken romatoid artrit hastalarının klinik ve ultrasonografik bulguları: 18 aylık takip çalışması

Objectives: The aim of our study is to perform the clinical, functional and ultrasonographic (US) follow-up of the early and very early RA patient which is naive among the disease modifying antirheumatic drugs (DMARDs) for 18 months and evaluate the relationship of these parameters with the radiological final state. Material and methos: This prospective study included 48 early RA (15 very early RA) patients. Gray scale US (GSUS), Power Doppler US (PDUS) examinations, DAS 28, HAQ, ESR, CRP were repeated at each visit (baseline, 1, 3, 6, 9, 12, 18 months). Hand, wrist, elbow, shoulder, knee joints and hand, wrist tendon structures were evaluated via GSUS and PDUS. Results: The improvement in the ESR, CRP levels is observed in the 1st month of the treatment (p=0.006). The statistically significant improvement in the HAQ, DAS 28 scores, total GSUS synovitis score, total PDUS tenosynovitis score, total GSUS tenosynovitis score, and total PDUS tenosynovitis score begins only in the 3rd month (p=0.007, p=0.003, p=0.001, p=0.009, p=0.002, p=0.004 respectively). In the laboratory, US monitoring of very early RA patients, it is similar to early RA patients. In the multiple linear regression model, only total GSUS synovitis scores, total PDUS synovitis scores at baseline and 1st continued to show an effect on the radiographic progression scores in the early RA patients (β=0.417, p=0011; β=0.549, p=0.028; β=0.476, p=0015; β=0.358, p=0.017, respectively). Conclusions: Radiographic damage progresses at the similar severity in early and very early RA patients. The most important factor affecting the radiographic damage progression is the severity of US synovitis at the baseline and in the 1st month, independently of the disease activity.

Affinity maturation shapes the function of agonistic antibodies to peptidylarginine deiminase type 4 in rheumatoid arthritis

ObjectivesThe citrullinating enzyme peptidylarginine deiminase type 4 (PAD4) is the target of a polyclonal group of autoantibodies in patients with rheumatoid arthritis (RA). A subgroup of such antibodies, initially identified...

Do Short and Sustained Periods of American College of Rheumatology/European League Against Rheumatism Remission Predict Functional and Radiographic Outcome in Early Rheumatoid Arthritis Patients With Low Overall Damage Progression?

To investigate whether remission at single and consecutive visits predicts good outcome in early rheumatoid arthritis (RA). The presence of remission according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) and other criteria (Boolean clinical, Clinical Disease Activity Index, Disease Activity Score [DAS], DAS in 28 joints, and Routine Assessment of Patient Index Data 3) was assessed in early RA patients during the first year of the Combination Therapy for Rheumatoid Arthritis light trial. Likelihood ratios were used to assess whether meeting the remission criteria at single visits (13, 26, 39, or 52 weeks) and consecutive visits (13 and 26, 26 and 39, or 39 and 52 weeks) predicted good outcome in the second year (52-104 weeks). Good outcome was defined for function (Health Assessment Questionnaire score consistently ≤0.5 and no deterioration), radiographic damage progression (no deterioration in Sharp/van der Heijde scores), and both ("overall good outcome"). Of the original 164 trial patients, 144 had evaluable data. In the second year, good functional outcome was observed in 35%, good radiographic outcome in 79%, and both in 28% of the patients. Almost all criteria predicted good functional and good overall outcome, at both single and consecutive visits; only single DAS remission did not significantly predict good overall outcome (P = 0.07). Sustained remission periods resulted in higher likelihood ratios than remission at single visits. None of the criteria predicted good radiographic outcome. Early RA patients who reached remission according to ACR/EULAR and other criteria during short or sustained periods were likely to retain good physical function in the subsequent months. Sustained remission periods were a stronger predictor than remission at single visits. However, in the setting of low overall damage progression, (sustained) remission was not predictive of good radiographic outcome.

Multireader assessment as an alternative to reference assessment to improve the detection of radiographic progression in a large longitudinal cohort of rheumatoid arthritis (ESPOIR)

IntroductionStructural damage progression is a major outcome in rheumatoid arthritis (RA). Its evaluation and follow-up in trials should involve radiographic scoring by 1 or 2 readers (reference assessment), which is...

Recent evidence comparing combination of conventional synthetic disease-modifying antirheumatic drugs with biologic disease-modifying antirheumatic drugs in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, disabling inflammatory arthritis often treated with a variety of disease-modifying antirheumatic drugs (DMARDs), whether conventional synthetic DMARDs (csDMARDs), targeted synthetic DMARDs (tsDMARDs), or biological DMARDs (bDMARDs). Most patients with RA are seropositive, have significant disease activity at presentation to the Rheumatologist and may have erosions at the time of diagnosis, all of which are poor prognostic factors. Patients with RA are often initially started on methotrexate (MTX), with addition of other DMARDs, the usual practice in the event of failure of/suboptimal response to MTX monotherapy. Since the recent guidelines by the European League against Rheumatism favor the use of bDMARDs over the combination of csDMARDs following the failure of MTX monotherapy in patients with such poor prognostic factors, we decided to review the recent literature comparing combination csDMARDs with bDMARDs. Long-term follow-up of landmark trials such as the Behandel-Strategieeen study (10 years) and NEO-RACo study (5 years) as well as other trials supports similar efficacy of both strategies in terms of clinical and functional outcomes. Whereas some studies have shown a minor but statistically significant progression of radiographic damage in those receiving combination of csDMARDs versus those on bDMARDs, others have not, further confirmed in a recent meta-analysis. Thus, keeping in mind, the similar efficacy and better cost-effectiveness of combination of csDMARDs, this should be the preferred strategy following failure of MTX monotherapy. bDMARDs should be reserved when combination csDMARDs fail, especially in an Indian scenario where most patients are poor and a majority of healthcare is not government-sponsored.

Ultrasound Is a Better Target Than Clinical Disease Activity Scores in Rheumatoid Arthritis

The assessment of joint inflammation is essential for diagnosing and monitoring response to therapies in patients affected by inflammatory arthropathies like rheumatoid arthritis (RA). For this, the use of musculoskeletal ultrasonography (US) with the power Doppler (PD) method has increased in the past decade. Also, US is known to detect B-mode synovitis and synovial Doppler activity in RA patients treated with either synthetic or biologic disease-modifying anti-rheumatic drugs. The US-detected synovitis has a predictive value in relation to radiographic damage progression and disease flare-up or relapse. Assessment by US ranges from wrist and hand joints to a comprehensive examination of 44 joints. Ultrasonographic (US) assessment has been shown to be useful in the management of RA and for monitoring the disease course. The application of US is helpful in such evaluations and is a complementary tool for classic methods used to detect RA, such as clinical evaluation and radiography, particularly when the MCP, PIP, and MTP joints are considered. Evidence has confirmed that GS and PD evaluation demonstrates a correlation between disease activity and degree of inflammation of synovial tissue. Moreover, US can be used for evaluating response to biological drugs. Naredo et al. have found a significant improvement in US parameters in RA patients undergoing therapy with a TNF blocking agent. Thus, US evaluation may be a valid method for monitoring response to biological therapy in RA patients. Finally, sonographic synovitis predicts erosion better than swollen joint count, C-reactive protein and erythrocyte sedimentation rate, US should be considered a promising treatment target in RA patients.

Stopping tumour necrosis factor-targeted biological DMARDs in rheumatoid arthritis.

The combined use of MTX and biological DMARDs (bDMARDs) targeting TNF has revolutionized treatment of RA, and clinical remission becomes a realistic treatment goal. After sustained remission, discontinuation of bDMARDs without disease flare has been emerging as an important theme from the risk-benefit point of view and economic burden. According to several studies, approximately half of early RA patients could discontinue TNF-targeted bDMARDs without clinical flare and functional impairment after obtaining low disease activity or remission by treatment with bDMARDs and MTX. For established RA, however, fewer patients sustained remission or low disease activity after the discontinuation of bDMARDs, compared with early RA. The results were controversial among studies, and the percentage of patients who could successfully discontinue bDMARDs ranged from 13 to 48% at 1 year after discontinuation. From the adalimumab discontinuation without functional and radiographic damage progression following sustained remission study and the induction of remission by infliximab in RA study, deep remission at discontinuation was a key factor for maintaining the treatment holiday of bDMARDs in established RA patients. However, such early intensive treatment would have the potential for reducing drug-induced adverse effects and reducing long-term medical costs, although the risks of worsening clinical, structural and functional outcomes should be considered, with careful monitoring.

Radiographic damage and progression of the cervical spine in ankylosing spondylitis patients treated with TNF-α inhibitors: Facet joints vs. vertebral bodies.

To investigate radiographic damage and 4-year progression of the cervical facet joints in a prospective observational cohort of AS patients treated with TNF-α inhibitors, to compare this with damage and progression of the cervical vertebral bodies, and to study the relation with patient characteristics and clinical outcome. Patients from the Groningen Leeuwarden AS (GLAS) cohort starting TNF-α inhibitors with baseline and 4-year radiographs were included. Cervical facet joints and vertebral bodies were scored by two independent readers according to the method of de Vlam and mSASSS, respectively. At baseline, 25 of 99 (25%) AS patients had partial or complete ankylosis of the cervical facet joints, whereas 51 (52%) patients had non-bridging or bridging syndesmophytes of cervical vertebral bodies. During 4 years, 13 (13%) patients developed new (partial) ankylosis of the facet joints, whereas 26 (26%) developed new (bridging) syndesmophytes. Facet joint damage and progression without involvement of the vertebral bodies were seen in 5 (5%) and 8 (8%) patients, respectively. Damage of facet joints was associated with longer disease duration, history of IBD/uveitis/psoriasis, higher disease activity, larger occiput-to-wall distance, higher mSASSS, and presence of syndesmophytes. Progression of the facet joints was associated with larger occiput-to-wall distance and more facet joint damage at baseline. Cervical facet joints were frequently involved in AS. During 4 years of TNF-α blocking therapy, 13% of the patients showed radiographic progression of cervical facet joints of which the majority did not show progression of vertebral bodies.

Self-reported flares are predictors of radiographic progression in rheumatoid arthritis patients in 28-joint disease activity score remission: a 24-month observational study.

BackgroundDisease flares are common in rheumatoid arthritis (RA) and are related to structural damage. However, few data on the impact of flares reported by patients on radiographic progression are available. Our aim was to investigate whether overall flares (OF), self-reported flares (SRF) and short flares assessed at the visit (SF) predict radiographic progression in RA patients in DAS28 (28-joint disease activity score) remission.MethodsWe reviewed the records of RA patients included in our database. We considered all patients who had a period of at least 24 months in remission (DAS28 < 2.6), stable biologic and synthetic disease-modifying anti-rheumatic drug treatment, no missing follow-up visits and hands and feet radiographs at the start and at the end of the 24-month follow up. Radiographic progression was considered as an increase in the van der Heijde modified total Sharp score >0. Patients were assessed every 3 months and flares were recorded. We defined SRF as any worsening of the disease reported by patients occurring in the time between visits and SF as an increase in DAS28 ≥ 2.6 or >0.6 from the previous visit assessed by the physician in one isolated visit. The impact of SRF, SF and OF on radiographic progression was assessed through multivariate regression analysis.ResultsOne hundred forty-nine patients were included. The median number (interquartile range) of OF was 1.00/year (0.50; 1.38), of SRF was 0.50/year (0.14; 1.00), and of SF was 0.34/year (0; 0.50). Eighteen patients (12.1 %) experienced a progression of radiographic damage. OF and SRF were significant predictors of radiographic progression: OR 3.27, 95 % CI 1.30, 8.22 and OR 3.63, 95 % CI 1.16, 11.36, respectively.ConclusionsOF and SRF are predictors of structural damage. Flares assessed at the visit, SF, do not impact on radiographic progression as they might underestimate the actual number of flares.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0986-1) contains supplementary material, which is available to authorized users.

Rheumatoid arthritis: an evolutionary force in biologics.

The advent of biologic therapy has transformed the outcomes of patients with Rheumatoid Arthritis (RA), but has also highlighted important issues for their development. Early attempts at T-cell driven therapies gave mixed results with difficulties extrapolating from non-human models to first in man trials. There is currently one T-cell modulating therapy - abatacept - licenced for use in RA. Cytokine inhibition has proven to be more fruitful with a number of anti-TNF and IL6 agents either licenced for use in RA or in development. The B-cell depleting therapy rituximab has also shown good efficacy as a chemotherapy agent repurposed for RA treatment. Overall the biologics show good efficacy in RA and have been shown to retard progression of radiographic joint damage. However, this benefit comes with a burden of increased infection risk and a financial cost significantly higher than conventional disease modifying therapies. As a result current UK licencing holds the biologics in reserve following failure of a conventional therapy and the presence of moderate to severely active disease. The long term use of the biologics in RA has highlighted the risk of immunogenicity, with significant proportions of patients developing anti-drug antibodies and losing therapeutic effect. The side effect profile and cost also raise the question around duration of therapy and trials of drug tapering following disease remission are now taking place with several biologic agents. Our inability to stratify patients to the most appropriate biologic drug (stratified or precision medicine) has also catalysed a large and critically important research agenda. Beyond identifying new biologic targets, the development of biosimilar agents will likely drive the future shape of the RA biologics market as lower cost alternatives are developed, thereby improving access to these therapies.

Serum adipokine levels in patients with ankylosing spondylitis and their relationship to clinical parameters and radiographic spinal progression.

Adipokines have metabolic and inflammatory functions but can also affect bone metabolism. The purpose of this study was to determine the relationship between serum levels of adiponectin, resistin, and visfatin and markers of inflammation, disease activity, and radiographic spinal progression in patients with ankylosing spondylitis (AS). Levels of adiponectin, resistin, and visfatin in the serum of 86 AS patients and 25 healthy controls were measured by enzyme-linked immunosorbent assay at baseline. Radiographic spinal progression was determined by the scoring of radiographs of the spine obtained at baseline and after 2 years. Mean (±SD) baseline levels of resistin and visfatin were significantly higher in AS patients than in healthy controls (11.6 ± 10.6 ng/ml versus 6.6 ± 3.2 ng/ml [P = 0.01] for resistin, and 20.9 ± 48.3 ng/ml versus 3.4 ± 2.6 ng/ml [P = 0.001] for visfatin). Adipokine serum levels did not correlate with disease activity or functional indices. Only resistin serum levels correlated with markers of inflammation. Baseline levels of visfatin, but not resistin or adiponectin, were significantly higher in patients with worsening of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) by ≥2 units after 2 years (n = 19) as compared to patients without mSASSS worsening (37.7 ± 57.8 ng/ml versus 16.1 ± 44.6 ng/ml; P = 0.029) and in patients with syndesmophyte formation/progression (n = 22) as compared to patients without such progression (37.1 ± 55.3 ng/ml versus 15.3 ± 44.8 ng/ml; P = 0.023). Visfatin levels of >8 ng/ml at baseline were predictive of subsequent radiographic spinal progression (adjusted odds ratio 3.6 for mSASSS progression and 5.4 for syndesmophyte formation/progression). Serum levels of resistin and visfatin are elevated in AS patients. Elevated visfatin levels at baseline are predictive of subsequent progression of radiographic damage in AS patients.

Is Structural Damage Evaluation by Traditional Radiographs Still Relevant in Rheumatoid Arthritis Clinical Trials?

To the Editor: Suppression of progression of radiographic damage in rheumatoid arthritis (RA) is the hallmark of an effective disease-modifying antirheumatic drug (DMARD), whether a biologic or nonbiologic drug. Its assessment has been part of all pivotal clinical trials, to obtain such a claim in the product monograph. In the original US Food and Drug Administration guidance document, placebo-controlled trials of 2–5 years were suggested as the method to demonstrate inhibition of radiographic progression. Recently a draft guidance document, not yet implemented, has suggested using alternative study designs because patients cannot be maintained on placebo for more than about 12 weeks1; however, it is mentioned that newer imaging techniques such as magnetic resonance imaging (MRI) and ultrasound are not yet validated. The European Medicines Agency still requires 1-year trials, or in exceptional cases 6 months can be … Address correspondence Dr. B. Haraoui, 1551 Ontario est, Montreal, Quebec H2L 1S6, Canada. E-mail: bharaoui{at}videotron.ca

THU0257 Acpa-Negative RA Patients Benefit from Initial Combination Therapy with Early Clinical Improvement - A Sub-Analysis of the Best Study

BackgroundAnti-citrullinated protein antibodies (ACPA)-positive (+) and ACPA-negative (−) rheumatoid arthritis (RA) patients may have different disease outcomes and may require different therapies.ObjectivesTo determine which treatment strategy in Disease Activity Score...

THU0131 Long Term Results of Inhibition of Radiographic Joint Damage Progression in Small and Medium and Large Joints in Patients with Rheumatoid Arthritis Treated with Tofacitinib Monotherapy

BackgroundTofacitinib is a novel oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). There was a study concerned with the efficacy for inhibiting the progression of radiographic...

AB0274 The Influence of Continuous Remission Rate on Functional Disability and Radiographic Progression for Rheumatoid Arthritis in A Japanese Observational Cohort

BackgroundOne goal of clinical remission in rheumatoid arthritis (RA) is to halt joint damage. The continuous clinical remission in established RA may result in improved function and reduced radiographic progression.ObjectivesThe...

A11: Assessment of Radiographic Progression in Patients With Polyarticular‐Course Juvenile Idiopathic Arthritis Treated With Tocilizumab: 2‐Year Data From CHERISH

Background/Purpose:The phase 3 CHERISH trial demonstrated the efficacy of tocilizumab (TCZ), an interleukin‐6 receptor inhibitor, in patients with polyarticular‐course juvenile idiopathic arthritis (pcJIA). This analysis investigated the progression of radiographic joint damage in patients with pcJIA treated with TCZ for up to 104 weeks in CHERISH.Methods:Patients 2 to 17 years old with ≥6 months' active pcJIA for whom methotrexate failed received open‐label (OL) TCZ according to body weight (BW) (BW ≥30 kg, 8 mg/kg [n = 119]; BW &lt;30 kg, randomly assigned 1:1 to 8 mg/kg [n = 34] or 10 mg/kg [n = 35]) every 4 weeks for 16 weeks. At 16 weeks, eligible patients (≥JIA ACR30 response) entered a 24‐week, randomized, double‐blind withdrawal period and were assigned 1:1 to placebo or continued TCZ. All patients entered an OL extension through week 104. Those receiving TCZ in all 3 parts were included in the continuous TCZ subgroup for which key radiographic end points were assessed. Radiographic progression was indicated as a positive change in adapted Sharp/van der Heijde score () (aSH) and/or a negative change in Poznanski score (), assessed on hand and wrist radiographs, from baseline to weeks 52 and 104.Results:Baseline and ≥1 postbaseline aSH and Poznanski scores were available for 45 and 35 patients, respectively, in the continuous TCZ subgroup and for 87 and 61 patients, respectively, in the total population. Reasons for missing data included early withdrawal, no consent, or unreadable radiographs (because of advanced damage resulting in unreliable measurements or growth plate fusion in postpubertal children), preventing assessment of Poznanski scores. Baseline demographics and disease characteristics were balanced for aSH and Poznanski populations and were similar to those for the full study population. At weeks 52 and 104, median changes from baseline aSH score of 0.5 (p = 0.70) and −1.0 (p = 0.11), respectively, and median changes from baseline Poznanski score of 0.3 (p = 0.07) and 0.6 (p = 0.004), respectively, indicating a lack of radiographic progression. With a cutoff of the smallest detectable difference, no radiographic progression was seen in 87.5% and 97.1% of patients based on aSH scoring and 93.5% and 96.0% of patients based on Poznanski scoring at weeks 52 and 104, respectively. Comparable proportions of the total radiographic population, including those exposed to placebo, remained radiographic progression free at week 104. Among the radiographic population, the annualized rates of progression to week 104 for aSH and Poznanski scores were 0.00 and 0.18, respectively.Conclusion:TCZ halted the progression of radiographic damage, leaving a large majority of pcJIA patients free of radiographic progression after 2 years of treatment.

A66: Assessment of Radiographic Progression in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Tocilizumab: 2‐Year Results From the TENDER Trial

Background/Purpose: A phase 3 trial (TENDER) demonstrated the efficacy of the interleukin-6 receptor inhibitor tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (sJIA) ([1, 2]). The aim of this study was to investigate the progression of radiographic joint damage in patients with sJIA treated with TCZ for up to 2 years in TENDER. Methods: One hundred twelve patients 2 to 17 years old with active, refractory sJIA of ≥6 months' duration and inadequate response to previous nonsteroidal anti-inflammatory drugs and oral corticosteroids were enrolled in TENDER. Patients were randomly assigned 2:1 to receive TCZ according to body weight (12 mg/kg <30 kg or 8 mg/kg ≥30 kg) or placebo intravenously every 2 weeks for 12 weeks. Patients then received open-label TCZ in the ongoing long-term extension. Radiographic progression was calculated as change in adapted Sharp/van der Heijde score (aSH) score and/or Poznanski score, assessed on hand and wrist radiographs, from baseline to weeks 52 and 104. Radiographic progression was indicated by a positive aSH score change or a negative Poznanski score change. Clinical efficacy end points included American College of Rheumatology (ACR) Pediatric (Pedi) 70/90 responses. Results: Baseline and ≥1 postbaseline aSH and Poznanski scores were available for 47 and 33 patients, respectively (reasons for missing x-rays: early withdrawal, no consent, unreadable x-rays). Baseline characteristics for patients with radiographic data were similar in the whole TCZ population (1). Patients with assessable aSH/Poznanski scores had 5.2-/4.8-year disease duration, 21.3/19.2 active joints, 20.0/18.2 joints with limitation of movement, and 53.9/59.2 mm/h erythrocyte sedimentation rate. At weeks 52 and 104, 20 and 19 patients, respectively, had aSH progression, and 8 and 8 patients, respectively, had Poznanski score progression. Median changes in aSH score from baseline to weeks 52 and 104 were 0 and 0.5, respectively (1). Median changes in Poznanski score from baseline to weeks 52 and 104 were 0.29 and 0.16, respectively (1). Table 1. Week 52 Week 104 a IQR, interquartile range. aSH score (n = 47), median (IQR) 0.00 (−8.70: 4.00) 0.50 (−7.50: 12.00) Poznanski score (n = 33), median (IQR) 0.29 (−0.05: 1.05) 0.16 (−0.01: 1.04) ACR Pedi 70 (n = 112), n/N (%) 92/106 (86.8) 57/65 (87.7) ACR Pedi 90 (n = 112), n/N (%) 67/106 (63.2) 46/65 (70.8) Conclusion: Although changes in radiographic scores over time were seen in many patients, on average, patients with sJIA did not experience noticeable progression of radiographic damage over 2 years of treatment with TCZ.

14-3-3η is a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage.

IntroductionThe aim of this study was to investigate whether 14-3-3η, a specific isoform of a family of proteins regulating processes such as cellular signalling, activates cell-signalling pathways and induces factors known to contribute to the pathophysiology of rheumatoid arthritis (RA). We also investigated whether 14-3-3η is associated with more severe disease in both early and established RA.MethodsWe investigated the effect of 14-3-3η on the activation of RA-relevant signalling cascades and induction of proinflammatory mediators that contribute to the joint damage process. 14-3-3η titres from 33 patients with early RA (mean RA duration = 1.8 months) and from 40 patients with established RA were measured in serum drawn at the 3-year time point of the Behandel Strategieën study. The relationship between 14-3-3η titres and standard clinical variables was investigated by correlation analysis. The association with radiographic damage and radiographic progression over at least a 2-year period was investigated using univariate and multivariate regression analyses.Results14-3-3η activated selected members of the mitogen-activated protein kinase (MAPK) family, mainly extracellular regulated kinase 1/2 and c-Jun kinase, but not p38MAPK. Activation by 14-3-3η, using levels spanning the concentration range found in RA patient serum, resulted in the induction of inflammatory transcripts such as interleukin 1 (IL-1) and IL-6 and factors linked to the joint damage process, such as receptor activator of nuclear factor κB ligand and matrix metalloproteinase 1. Serum 14-3-3η correlated significantly with rheumatoid factor (RF) (r = 0.43) and anticitrullinated protein antibodies (ACPAs) (r = 0.31) in the early RA cohort, but not with C-reactive protein (CRP) or the Disease Activity Score in 28 joints in either cohort. Serum 14-3-3η concentrations were significantly higher in patients with radiographically assessed joint damage and in those who had radiographic progression. By multivariate analysis, we show that 14-3-3η complemented markers such as CRP, RF and ACPA in informing RA radiographic status and/or progression.ConclusionsExtracellular 14-3-3η activates key signalling cascades and induces factors associated with the pathogenesis of RA at concentrations found in patients with RA, and its expression is higher in patients with radiographic damage and RA progression.

Frequency of Radiographic Damage and Progression in Individual Joints in Children With Juvenile Idiopathic Arthritis

To evaluate the presence and progression of radiographic joint damage, as assessed with the adapted Sharp/van der Heijde score (SHS), in individual joints in the hand and wrist in patients with juvenile idiopathic arthritis (JIA) and to compare progression of damage among different JIA categories. A total of 372 radiographs of both wrists and hands obtained at first observation and at last followup visit (after 1-10 years) in 186 children with polyarticular-course JIA were evaluated. All radiographs were scored using the adapted SHS by 2 independent readers. Radiographic assessment included evaluation of joint space narrowing (JSN) and erosions on baseline and last followup radiographs and of progression of radiographic changes from baseline to last followup radiographs. Both JSN and erosions occurred in all adapted SHS areas. Overall, radiographic damage and progression were more common in the wrist and less common in metacarpophalangeal (MCP) joints. The hamate and capitate areas appeared particularly vulnerable to cartilage loss. Erosions were identified most frequently in the hamate and capitate bones as well as in the second and third metacarpal bases. Patients with extended oligoarthritis were distinctly less susceptible to JSN in hand joints, whereas patients with polyarthritis showed a greater tendency to developing erosions in hand joints. Radiographic joint damage and progression in our patients with JIA were seen most commonly in the wrist and less commonly in MCP joints. The frequency and localization of structural abnormalities differed markedly across disease categories.

Is radiographic progression of late-onset rheumatoid arthritis different from young-onset rheumatoid arthritis? Results from the Swiss prospective observational cohort

RA can be categorized into late-onset RA (LORA, >60-65 years) and young-onset RA (YORA, 30-55 years), depending on the patient's age at disease onset. Since the average age of the population is continuously increasing, LORA will most probably gain in importance in the future. Despite this growing importance, LORA has not been the focus of much interest in the past. The aim of this study was to analyse radiographic damage progression of early disease in LORA compared with YORA patients. We included all patients from the Swiss RA registry, Swiss Clinical Quality Management in RA, with recent-onset arthritis, either RA (disease duration ≤1 year) or undifferentiated arthritis, as diagnosed by the data-entering physician. Patients were followed for 5 years. The cut-off between YORA and LORA was operationally set at 60 years of age. The primary outcome of this study was disease progression and activity, which was assessed based on the 28-joint DAS (DAS28) and the progression of joint erosions using a validated scoring system (Ratingen score). A total of 592 patients with early disease were analysed. The age at disease onset had a Gaussian distribution, with a single peak at 54 years of age; 366 patients were categorized as YORA and 226 as LORA at disease onset. DAS28 scores were significantly higher among LORA as compared with YORA patients (4.8 vs 4.5, P = 0.049). Corticosteroids were used in 68% of LORA patients as a first-line treatment, compared with 25.4% in YORA patients (χ(2) test: 54.58; P < 0.0001). In contrast, DMARDs were used in 100% of the YORA patients as first-line treatment, compared with 91.2% of the LORA patients. During follow-up, new glucocorticoids, synthetic DMARDs or biologic DMARDs were initiated in 32.8%, 61.1% and 14.1% of all YORA patients and 17.5%, 54.6% and 6.6% of LORA patients, respectively (χ(2) test: 7.08, 22.53, 54.4; all P < 0.01). The DAS28 scores decreased in both groups during the observed time period, and the initial differences in disease activity vanished after 6 months and during the subsequent follow-up. The Ratingen score was higher in LORA than in YORA patients at inclusion (12.7 vs 5.6, P < 0.0001). The rate of radiographic progression at 5 years was similar when comparing LORA and YORA (3.3 vs 2.6, respectively, P = 0.64). The Ratingen scores at onset and during follow-up over 5 years did not clearly separate LORA and YORA into two groups, but rather, increased linearly when comparing the patients in groups per decade from 20 to 92 years of age. Our results did not show LORA as a separate subgroup of RA with a different prognosis with regard to radiographic progression.