Progression Of Structural Damage Research Articles

Potential value of cartilage and bone soluble biomarkers in evaluating joint damage in juvenile idiopathic arthritis

Serum biomarkers of bone and cartilage turnover were found to predict structural damage progression in Rheumatoid Arthritis (RA). Their potential value in Juvenile Idiopathic Arthritis (JIA) has never been explored.

Tofacitinib versus Methotrexate in Rheumatoid Arthritis

BackgroundMethotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate.MethodsWe randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (≥70% reduction in the number of both tender and swollen joints and ≥70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician).ResultsMean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as compared with 0.8 points in the methotrexate group [P<0.001 for both comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with 12.0% of patients in the methotrexate group (P<0.001 for both comparisons). Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer (including three cases of lymphoma) developed in 5 patients who received tofacitinib and in 1 patient who received methotrexate. Tofacitinib was associated with increases in creatinine levels and in low-density and high-density lipoprotein cholesterol levels.ConclusionsIn patients who had not previously received methotrexate or therapeutic doses of methotrexate, tofacitinib monotherapy was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage. The benefits of tofacitinib need to be considered in the context of the risks of adverse events. (Funded by Pfizer; ORAL Start ClinicalTrials.gov number, NCT01039688.)

Baseline serum interleukin-34 levels independently predict radiographic progression in patients with rheumatoid arthritis.

The aim of our observational study was to investigate the clinical significance of interleukin (IL)-34, a novel osteoclastogenic cytokine, for predicting structural damage in patients with rheumatoid arthritis (RA). Serum IL-34 levels were measured in 100 RA patients, 36 patients with ankylosing spondylitis (AS), and 59 gender- and age-matched healthy individuals using an enzyme-linked immunosorbent assay. We also measured IL-34 concentrations in synovial fluid (SF) samples from 18 RA patients and 19 osteoarthritis (OA) patients. Progression of structural damage was assessed in 81 patients with RA by plain radiographs using the modified Sharp/van der Heijde score (SHS) at baseline and after an average 1.6-year follow-up period. Serum IL-34 levels were significantly higher in patients with RA (p < 0.001) or AS (p < 0.001) than in healthy controls. SF IL-34 levels were also significantly higher in RA patients than in OA patients (p < 0.001). In RA, serum IL-34 levels were associated with rheumatoid factor positivity (p = 0.01), current smoking (p < 0.01), erythrocyte sedimentation rate (p = 0.01), and C-reactive protein levels (p < 0.01), but not with disease activity score 28. ΔSHS/year was positively correlated with serum IL-34 levels (r = 0.443, p < 0.001). In multivariate logistic regression analyses, serum IL-34 level was an independent risk factor for radiographic progression. These results suggest that IL-34, a novel osteoclastogenic cytokine, plays a role in RA-associated joint damage and is a potential biomarker for predicting subsequent radiographic progression in patients with RA.

SAT0431 Inflammatory Ultrasound Features Show Strong and Independent Associations with Progression of Structural Damage after 2.5 Years of Follow-Up in Hand Osteoarthritis Patients

BackgroundSeveral cross sectional studies have shown that inflammatory ultrasound (US) features are frequently found in hand osteoarthritis (OA). Up till now, no follow up studies have been performed to study...

SP0065 What is the Target for Ra? “The Imaging Target”

The best imaging target for remission is demonstration that no progression of structural damage has occurred. Radiographs are able only to show inhibition of structural damage over a 6 to...

SAT0185 Assessment of Fifth Metatarsophalangeal Joint Erosion in Rheumatoid Arthritis by Ultrasonography

BackgroundJoint erosions in RA correlate with structural damage progression and functional capacity. Therefore, detection and the follow-up of erosions are of paramount importance for RA diagnosis, monitoring and determining of...

AB0675 Infliximab in Ankylosing Spondylitis: Effect on Structural Damage Progression

BackgroundTumor necrosis factor-α (TNF-α) inhibition has been evolutionary in the treatment of ankylosing spondylitis (AS). Conventional radiography reflects chronic structural damage in AS rather than the underlying inflammatory processes that...

AB1000 Assessing the Impact of Subcutaneous Abatacept in Inhibiting Structural Damage in Rheumatoid Arthritis by Low Field Magnetic Resonance Imaging and X-Ray

BackgroundRheumatoid arthritis (RA) treatment has shifted from reducing symptoms to earlier inhibition of disease progression, thus preventing irreversible structural damage and disability. Detection of synovitis (SYN), osteitis (OST), and erosions...

SP0208 Mri Comes of AGE for Clinical Trials in Rheumatoid Arthritis

The past two decades have seen unprecedented advances in therapy for rheumatoid arthritis (RA), with several effective biologics introduced since 1998. Radiography played a central role in validating each of...

SAT0257 Clinical and Radiographic Effects after 52-Week of Adding Tocilizumab or Switching to Tocilizumab in RA Patients with Inadequate Response to Methotrexate: Results from A Prospective Randomized Controlled Study (Surprise Study)

BackgroundThe SURPRISE study is an open-label trial comparing the strategy of tocilizumab (TCZ) plus methotrexate (MTX) (ADD-ON) with the strategy of switching to TCZ (SWITCH) in Japanese rheumatoid arthritis (RA)...

SP0126 How to Treat (HOT) Spondyloarthritis?

Spondyloarthritis (SpA) can be split into axial (ax) and peripheral SpA, according to the predominant clinical presentation. Major progresses have been made over the last decade defining optimal treatment for...

SP0139 A Tool to Identify Past or Present Rheumatoid Arthritis Flare from Both Patient and Physician Perspective

Rheumatoid arthritis (RA) patients with unstable and fluctuating disease activity have been shown to be at risk of structural damage progression. Despite considerable efforts dedicated to the assessment of RA...

FRI0278 The First Early Rheumatoid Arthritis, Certolizumab Pegol, Multicenter, Double-Blind, Randomized, Parallel-Group Study: C-Opera, in Patients Fulfilling the 2010 Acr/Eular Classification Criteria, Demonstrates Inhibition of Joint Damage Progression

BackgroundAssessment of structural damage progression, clinical efficacy and safety in patients with early-stage rheumatoid arthritis (RA) naïve to methotrexate (MTX) and with poor prognostic factors with certolizumab pegol (CZP) has...

OP0079 Ustekinumab is Effective in Inhibiting Radiographic Progression in Patients with Active Psoriatic Arthritis: Integrated Data Analysis of Two Phase 3, Randomized, Placebo-Controlled Studies

ObjectivesTo evaluate the effect of ustekinumab (UST), an IL-12/23 p40 inhibitor, on inhibition of progression of structural damage in patients with active psoriatic arthritis (PsA) at wk24 and wk52 in...

Longterm safety, efficacy, and inhibition of structural damage progression over 5 years of treatment with abatacept in patients with rheumatoid arthritis in the abatacept in inadequate responders to methotrexate trial.

Evaluate the safety and efficacy of longterm abatacept (ABA) treatment over 5 years in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). Patients from the 1-year, double-blind Abatacept in Inadequate Responders to Methotrexate (AIM) study (NCT00048568) received open-label ABA (∼10 mg/kg) in the longterm extension (LTE). Safety was assessed for patients who received ≥ 1 ABA dose, and efficacy for patients randomized to ABA and treated in the LTE. Radiographs were evaluated for changes in Genant-modified Sharp scores. Out of 652 patients, 539 entered the LTE (ABA, n = 378; placebo, n = 161). At Year 5, 72.4% were ongoing; discontinuation rates declined over time. Incidence rates of serious adverse events, serious infections, malignancies, and autoimmune events were 13.87, 2.84, 1.45, and 0.99 events/100 patient-years exposure, respectively. American College of Rheumatology 20 response was 82.3% (n = 373) and 83.6% (n = 268) at years 1 and 5, respectively. Disease Activity Score 28 C-reactive protein (DAS28-CRP) < 2.6 and ≤ 3.2 were achieved by 25.4% and 44.1% of patients at Year 1 (n = 370), and 33.7% and 54.7% at Year 5 (n = 267), respectively. Mean changes in DAS28-CRP and Health Assessment Questionnaire-Disability Index at Year 1 [-2.83 (n = 365) and -0.68 (n = 369)] were maintained at Year 5 [-3.14 (n = 264) and -0.77 (n = 271)] for patients continuing treatment. Of them, 59.5% (n = 291) and 45.1% (n = 235) remained free from radiographic progression at years 1 and 5, respectively. In MTX-refractory patients with RA, longterm ABA treatment was well tolerated and provided consistent safety and sustained efficacy, with high patient retention. Radiographic progression continued to be inhibited with ongoing treatment.

Inflammatory ultrasound features show independent associations with progression of structural damage after over 2 years of follow-up in patients with hand osteoarthritis

ObjectiveTo study the development of inflammatory features and it's relation to structural damage over a 2.3-year period in patients with hand osteoarthritis (HOA).MethodsSynovial thickening, effusion and power Doppler signal (PDS)...

Micromechanical Modeling of Onset and Progression of Damage in Composite Structures

Prediction of onset and progression of damage in composite materials with the capability of dealing with complex loadings and the heterogeneity of the constituents using appropriate failure criterion is the focus of this study. The micromechanics of failure (MMF), based on a unit cell model which describes the microstructure of the composite that uses independent failure criterion for each constituent, is proposed in this exercise. As the failure has been predicted at constituent level, micromechanics-based failure criteria show more predictive capabilities in heterogeneous composite structures. A modified failure prediction model has been proposed in this work to better capture the onset of failure, constituent's failure, and damage initiation in composites. The progression of damage is predicted using the micromechanics failure criteria with progressive degradation model until complete failure of the composite structure.

Efficacy and Safety of Certolizumab Pegol in Rheumatoid Arthritis: Meeting Rheumatologists’ Requirements in Routine Clinical Practice

Certolizumab pegol, a pegylated Fab' anti-tumour necrosis factor (TNF)-α agent, has shown efficacy in patients with rheumatoid arthritis (RA) unresponsive to previous treatment. In key randomised controlled trials involving patients with moderate to severe RA and an inadequate response to methotrexate or one or more disease-modifying antirheumatic drug (DMARD), the efficacy of certolizumab pegol, as monotherapy or with methotrexate, was similar to that reported in other anti-TNF clinical studies, with 60% or fewer of patients achieving American College of Rheumatology 20% improvement in RA. Rapid clinical response was also seen, with significant differences evident at week 1, and efficacy maintained at study end and in open-label extensions. Adding certolizumab pegol to non-biological DMARDs is efficacious in other RA populations. In the CERTAIN study, certolizumab increased remission rates, prevented disease worsening and improved work productivity and daily activity in patients with low to moderate RA. In the REALISTIC study, rapid and consistent clinical responses were observed in a diverse group of anti-TNF-eligible RA patients representing those seen in clinical practice. In the RAPID studies, rapid and sustained reduction in RA signs and symptoms, inhibition of structural joint damage progression, and improved physical function were seen with certolizumab pegol plus methotrexate versus methotrexate alone in RA patients with an incomplete response to methotrexate. Certolizumab pegol was generally well-tolerated in clinical trials, although long-term observational data are not yet available. Current data suggest that certolizumab pegol suits a 'treat to target' approach, providing rapid and sustained improvements in RA signs and symptoms, and beneficial effects on workplace and home productivity in patients with RA.

Evaluation of medication treatment for Alzheimer's disease on clinical evidence

Objective To formulate the best treatment plan for Alzheimer's disease patients by evaluating the therapeutic efficacy and side effect of various evidence-based programs. Methods Alzheimer's disease, donepezil, rivastigmine, galantamine, memantine, rosiglitazone, etc. were defined as retrieval words. PubMed, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI) databases were used with applying of manual searching. Systematic reviews, randomized controlled trials (RCT), controlled clinical trials and case-observation studies were collected and evaluated by Jadad Scale. Results After screening, 33 selected resources included 14 systematic reviews, 14 randomized controlled trials, 4 controlled clinical trials and 1 case-observation study. According to Jadad Scale, total 28 articles were evaluated to be high quality (12 with score 4, 10 score 5, 6 score 7), and 5 were low quality with score 3. It was summarized as follows: 1) Alzheimer's disease is a progressive neurodegenerative disease for which no cure exists. To date, only symptomatic treatments with cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and an N-methyl-D-aspartate (NMDA) receptor noncompetitive antagonist (memantine), are effective and well tolerated to counterbalance the neurotransmitter disturbance, but cannot limit or impact on disease progression. 2) Disease modifying drug is an potential agent, with persistent effect on slowing the progression of structural damage, and can be detected even after withdrawing the treatment. Many types of disease modifying drugs are undergoing clinical trials. Conclusions Using evidence-based medicine methods can provide best clinical evidence on Alzheimer's disease treatment. doi: 10.3969/j.issn.1672-6731.2014.03.009

Inflammatory ultrasound features show strong and independent associations with progression of structural damage after 2.5 years of follow-up in hand osteoarthritis patients

Inflammatory ultrasound features show strong and independent associations with progression of structural damage after 2.5 years of follow-up in hand osteoarthritis patients