Progression Of Structural Damage Research Articles

AB0579 Abatacept in rheumatoid arthritis: Clinical and imaging considerations

ObjectivesTo investigate the efficacy and safety of abatacept in patients with rheumatoid arthritis (RA) and to describe abatacept survival rates and reasons for discontinuation. Additionally, to investigate the effectiveness of...

SAT0486 Early MRI Measures Independently Predict 1- and 2- Year X-Ray Progression: Results from a Large Clinical Trial

ObjectivesEarly predictors of progression in structural joint damage in RA are lacking. We evaluated if early MRI measures of inflammation & erosion at baseline (BL), 12 & 24wks could predict...

FRI0282 Insights into progression of structural damage of sacroiliac joints in patients with axial spondyloarthritis: Introduction of new scoring system for radiographic sacroiliitis

BackgroundThe established scoring system of radiographic sacroiliitis implemented in the mNY criteria for ankylosing spondylitis (AS) does not differentiate between different types of structural damage and does not account for...

THU0093 Clinical, radiographic, and immunogenic effects after 1 year of tocilizumab (TCZ)-based treatment strategy with and without methotrexate (MTX) in RA: The act-ray study

Background24-week data from ACT-RAY comparing an add-on strategy (TCZ+MTX) with a switch strategy (TCZ+placebo [PBO]) in MTX-IR patients have been previously reported, demonstrating relevant clinical and radiographic benefit without a...

THU0225 Tofacitinib Monotherapy is Effective in Methotrexate-NaÏVe Patients with Disease Duration Less Than 6 Months: a Post-HOC Analysis of Early Rheumatoid Arthritis Subjects in a Phase 3 Trial

BackgroundTofacitinib is a novel oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA).ObjectivesTo assess the efficacy of tofacitinib monotherapy in patients (pts) with early RA (eRA), as...

SP0188 Structural progression in RA remission: Can MRI predict it?

Remission has become in the last few years an accessible objective in the management of rheumatoid arthritis (RA) patients due to treatment improvement and the development of international guidelines. The...

FRI0177 52-week results of clinical, radiographic and pharmacokinetic assessments: Golimumab, a human anti-TNF monoclonal antibody, administered subcutaneously every four weeks in patients with active rheumatoid arthritis despite methotrexate therapy

ObjectivesTo assess the efficacy and safety of golimumab (GLM) in Japanese patients (pts) with active RA despite MTX therapy.MethodsGO-FORTH is a multicenter, randomized, double-blind, placebo (PBO)-controlled study in pts with...

FRI0199 In patients with established RA, abatacept efficacy is independent of baseline annual radiographic progression rate

BackgroundIn the Phase III, double-blind, placebo (PBO)-controlled AIM study, abatacept (ABA)+ MTX significantly inhibited structural damage progression vs PBO+MTX in pts with established RA and inadequate response to MTX.1Sustained inhibition...

AB0555 Are there differences in biomarkers of cartilage and bone turnover between patients with familial versus sporadic early spondiloarthritis?

ObjectivesOur purpose was analyze potential differences in biomarkers of cartilage and bone turnover between patients with familial early spondyloarthritis (SpA) and sporadic early EspA.MethodsA cross-sectional study of baseline visits from...

FRI0178 Five-year safety and efficacy of golimumab in methotrexate-naïve patients with rheumatoid arthritis: final study results of the phase 3, randomized, placebo-controlled go-before trial

ObjectivesFinal 5yr safety and efficacy results of subcutaneous golimumab (GLM)+/-MTX evaluated in a phase 3 trial (GO-BEFORE) of MTX-naïve pts with rheumatoid arthritis (RA) are reported.MethodsPts were randomized to PBO+MTX,...

From inhibition of radiographic progression to maintaining structural integrity: a methodological framework for radiographic progression in rheumatoid arthritis and psoriatic arthritis clinical trials

Usually, a clinical trial in rheumatoid arthritis and psoriatic arthritis aiming to demonstrate that a new antirheumatic drug treatment can inhibit progression of structural damage has a ‘superiority design’: The...

Progression of structural damage is not related to rituximab serum levels in rheumatoid arthritis patients

The most cost-effective dosing regimen for rituximab treatment in RA is currently unknown. The objective of this study is to determine whether low rituximab serum levels are associated with progression of structural damage in RA patients. Sixty-two RA patients were treated with rituximab in three different centres. Structural damage was assessed on radiographs of hands and feet before and 1 year after therapy using the Sharp-van der Heijde scoring method (SHS). Patients were divided into progressors vs non-progressors based on different cut-off values. Rituximab serum levels were measured by sandwich ELISA after 4 and 12 weeks (Leiden University Medical Center and University Medical Centre, Utrecht cohorts) or 4 and 16 weeks (Academic Medical Center/University of Amsterdam cohort). There was no difference in rituximab levels between progressors and non-progressors 4 weeks and 12 or 16 weeks after initiation of treatment in the different cohorts. There was also no correlation between rituximab levels at week 4 or week 12 or 16 and change in SHS score after 1 year. Low rituximab serum levels are not associated with progression of structural damage in RA patients. The results do not support the use of dosages higher than 2 × 1000 mg rituximab to inhibit progression of joint destruction.

Validation of damage modelling in composite fuselage structures under high velocity impact

The paper discusses finite element (FE) simulation methods in use for predicting impact damage in advanced composite structures. Before these simulation tools are accepted by the industry for design and certification of composite aircraft structures, composites damage models have to be developed, implemented in commercial FE codes and validation studies at specimen and substructure level have to be performed. For vulnerability analysis, the DLR uses meso-scale composites ply damage models with an energy-based delamination failure criteria in explicit FE codes to study damage progression in composite structures under impact. The methods developed are summarised in the paper and applied to predict impact damage in stiffened aircraft panels and novel foldcore sandwich structures from hard debris. Issues concerned with use of such computational methods for certification by analysis are discussed.

Tofacitinib (CP‐690,550) in patients with rheumatoid arthritis receiving methotrexate: Twelve‐month data from a twenty‐four–month phase III randomized radiographic study

The purpose of this 24-month phase III study was to examine structural preservation with tofacitinib in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Data from a planned 12-month interim analysis are reported. In this double-blind, parallel-group, placebo-controlled study, patients receiving background MTX were randomized 4:4:1:1 to tofacitinib at 5 mg twice daily, tofacitinib at 10 mg twice daily, placebo to tofacitinib at 5 mg twice daily, and placebo to tofacitinib at 10 mg twice daily. At month 3, nonresponder placebo-treated patients were advanced in a blinded manner to receive tofacitinib as indicated above; remaining placebo-treated patients were advanced at 6 months. Four primary efficacy end points were all analyzed in a step-down procedure. At month 6, response rates according to the American College of Rheumatology 20% improvement criteria for tofacitinib at 5 mg and 10 mg twice daily were higher than those for placebo (51.5% and 61.8%, respectively, versus 25.3%; both P < 0.0001). At month 6, least squares mean (LSM) changes in total modified Sharp/van der Heijde score for tofacitinib at 5 mg and 10 mg twice daily were 0.12 and 0.06, respectively, versus 0.47 for placebo (P = 0.0792 and P ≤ 0.05, respectively). At month 3, LSM changes in the Health Assessment Questionnaire disability index score for tofacitinib at 5 mg and 10 mg twice daily were -0.40 (significance not declared due to step-down procedure) and -0.54 (P < 0.0001), respectively, versus -0.15 for placebo. At month 6, rates of remission (defined as a value <2.6 for the 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate) for tofacitinib at 5 mg and 10 mg twice daily were 7.2% (significance not declared due to step-down procedure) and 16.0% (P < 0.0001), respectively, versus 1.6% for placebo. The safety profile was consistent with findings in previous studies. Data from this 12-month interim analysis demonstrate that tofacitinib inhibits progression of structural damage and improves disease activity in patients with RA who are receiving MTX.

MRI comes of age in RA clinical trials

The success of modern rheumatoid arthritis (RA) therapies and treatment strategies has led to extended placebo phases being unethical in RA randomised controlled trials (RCTs). Modern trials therefore increasingly involve...

Axial spondyloarthritis: is there a treatment of choice?

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the axial skeleton (sacroiliac joints and spine). Nonradiographic axSpA (axSpA without radiographic sacroiliitis) and ankylosing spondylitis (AS; radiographic form of axSpA) are considered nowadays as two consecutive stages of one disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective against the major symptoms of axSpA (pain and stiffness) and may have disease-modifying properties including retarding progression of structural damage in the spine. Therefore, NSAIDs, unless contraindicated, are the treatment of choice for the majority of patients with axSpA. Beyond NSAIDs, only tumour necrosis factor (TNF) α blockers are effective and approved for the treatment of active axSpA. Several novel drugs (i.e. monoclonal antibodies targeting interleukin-17, interleukin-12/23, inhibitors of phosphodiesterase-4 and kinases), which might be effective in axSpA, are currently under investigation. Pharmacological therapy of axSpA should always be combined with nonpharmacological treatment including education and regular exercise/physiotherapy.

Espondiloartritis

Spondyloarthritis is a group of diseases related but different clinical expression: psoriatic arthritis, arthritis of inflammatory bowel disease, reactive arthritis, a subgroup of juvenile idiopathic arthritis and ankylosing spondylitis (the prototypic and best studied). In the last five years there have been significant advances in several areas to help better recognition of spondyloarthritis as a clinical entity and its classification. A better understanding of the pathophysiological mechanisms and genetic factors related to inflammation and structural damage. In addition, new clinical and imaging results are allowing a better assessment of treatment options. These continue to highlight biological therapies, especially the blocking tumor necrosis factor alpha and therapeutic breakthrough, however the exact role of physiotherapy, treatment with NSAIDs and other biological treatments are still not known intimately.The main challenges with direct application to clinical practice for the next decade are the development of tools for early diagnosis of treatment can modulate (or inhibit) the progression of structural damage and induce long-term remissions without treatment.

Bone Effects of Biologic Drugs in Rheumatoid Arthritis

Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNFα, IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNFα, IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

&lt;b&gt;2．IL-6 標的薬&lt;/b&gt;

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates immune responses and inflammatory reactions. Deregulated over-production of IL-6 plays pathological roles in rheumatoid arthritis (RA). Therefore, blocking IL-6 actions can be a treatment for this disease. Tocilizumab is a humanized anti-human IL-6 receptor antibody and has just become available worldwide. Tocilizumab specifically blocks IL-6 binding to both membrane-bound and soluble forms of IL-6 receptor, and inhibits IL-6 signal transduction. Tocilizumab, both as monotherapy and in combination with methotrexate (MTX), has been shown to be effective in patients with RA refractory to MTX or other disease-modifying anti-rheumatic drugs. Tocilizumab also has therapeutic benefit in patients who are refractory to tumor necrosis factor inhibitors. Moreover, tocilizumab retards the progression of structural joint damage. The safety profile of tocilizumab is acceptable based on a large registry data. The agent is now approved in more than 100 countries. (Jpn J Clin Pharmacol Ther 2013; 44(1): 9-14)

IMPACT OF TOCILIZUMAB THERAPY ON STRUCTURAL JOINT DAMAGE PROGRESSION IN RHEUMATOID ARTHRITIS

Objective — to evaluate the impact of tocilizumab (TCZ) therapy on progression of joint destruction and rheumatoid arthritis (RA) inflammatory activity in 48 weeks after initiation of treatment. Material and methods. 42 RA patients who received 6 intravenous TCZ infusions at dose 8 mg/kg given once every 4 weeks alongside with stable anti-inflammatory and glucocorticoid DMARDs were evaluated. EULAR criteria, as well as SDAI and CDAI disease activity indices were used to evaluate the efficacy of TCZ therapy. Radiographs of the hand and distal feet of each patient were obtained at baseline before initiating TCZ therapy and then at 48 weeks. Absence of radiographic progression was defined as total Sharp/van der Heijde score change ≤0. Results. At Week 48 the following values of indices — DAS28 — 4,69 [3,86; 5,44], SDAI — 17,8 [10,7; 29,5], CDAI — 17,1 [7,2; 26,2] — were corresponding to moderate disease activity and were significantly lower than the baseline values. Remission by DAS28 was observed in 11,9% patients, by SDAI — in 7,1%, and by CDAI — in 9,5%. Baseline median total Sharp/van der Heijde score equaled to 78 [46; 122], the number of erosions — to 10,5 [2; 35], and the number ofjoint space narrowing — to 67 [42; 98], while at Week 48 the values of these indices were — 80 [44; 130], 13,5 [1,5; 34] and 69,5 [38; 110], respectively, with signs of radiographic progression in 9 (22,5%) patients. There were no significant differences in the number of erosions and total Sharp scores in subgroups of patients with low, moderate or high disease activity by SDAI & CDAI and sustainable remission at Week 48. Conclusion. Clinical outcomes after 24-week TCZ therapy are indicative of its' clinical effectiveness and a potential to inhibit structural joint damage progression in RA patients.