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Find video protocols related to scientific articles indexed in Pubmed.
Treatments for Nail Psoriasis: A Systematic Review by the GRAPPA Nail Psoriasis Work Group.
J. Rheumatol.
PUBLISHED: 11-03-2014
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Nail involvement in psoriatic diseases causes significant physical and functional disabilities. Evaluating, measuring, and treating nail involvement is important in improving the health outcomes and quality of life among patients with psoriasis and psoriatic arthritis (PsA). We performed a systematic analysis of the literature on nail psoriasis to help inform an update of treatment recommendations by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
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Systematic Review of Treatments for Psoriatic Arthritis: 2014 Update for the GRAPPA.
J. Rheumatol.
PUBLISHED: 11-03-2014
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Psoriatic arthritis (PsA) is a chronic systemic inflammatory disorder characterized by the association of arthritis and periarticular inflammation in patients with psoriasis. In addition to a heterogeneous and variable clinical course, PsA is complex and multifaceted and may include prominent involvement in the peripheral and axial diarthrodial joints, the skin and nails, and in periarticular structures such as entheses. Simultaneous inflammation in the skin and musculoskeletal structures in a single patient, a relatively common scenario, often leads to marked decrease in function and quality of life. Thus, it is essential for the clinician to document the extent of disease involvement and craft a therapeutic plan that addresses the different domains of disease. In an effort to update previous treatment recommendations developed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), several evidence-based, systemic reviews of therapies for PsA were completed, analyzed, and circulated for consensus.
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A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of 2 Dosing Regimens of Fostamatinib in Patients with Rheumatoid Arthritis with an Inadequate Response to a Tumor Necrosis Factor-? Antagonist.
J. Rheumatol.
PUBLISHED: 09-15-2014
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Our 24-week study (NCT01197755; OSKIRA-3) compared the efficacy and safety of fostamatinib versus placebo in patients taking background methotrexate treatment with active rheumatoid arthritis (RA) and an inadequate response to a single tumor necrosis factor-? antagonist.
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Comprehensive disease control (CDC): what does achieving CDC mean for patients with rheumatoid arthritis?
Ann. Rheum. Dis.
PUBLISHED: 08-19-2014
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This study assessed the impact of simultaneous achievement of clinical, functional and structural efficacy, herein referred to as comprehensive disease control (CDC), on short-term and long-term work-related outcomes, health-related quality of life (HRQoL), pain and fatigue.
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Psoriatic arthritis: current therapy and future approaches.
Rheumatology (Oxford)
PUBLISHED: 08-14-2014
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PsA is a systemic inflammatory condition that affects 20-30% of patients with psoriasis. It is characterized by potential involvement of diverse tissues, including peripheral and axial joints, enthesitis, dactylitis and skin and nail disease. The degree of involvement in each domain can vary over time in individual patients and can differ substantially between PsA patients. The clinical heterogeneity along with the varying extent of severity and activity can pose significant challenges to treatment. Although some studies had suggested immunopathophysiological similarities between PsA and RA, more recently important distinctions have been defined. Similarly, although some immunomodulatory therapies have proved effective for both PsA and RA, recent data suggest distinct responses to certain targeted therapies. Herein, current DMARDs and biologic agents as well as the potential role of emerging therapeutics will be reviewed.
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Can we improve the performance and reporting of investigator-initiated clinical trials? Rheumatoid arthritis as an example.
Ann. Rheum. Dis.
PUBLISHED: 08-11-2014
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Investigator-initiated trials, some of which have been referred to as comparative effectiveness trials, pragmatic trials, or strategy trials, are sometimes considered to be of greater clinical importance than industry-driven trials, because they address important but unresolved clinical questions that differ from the questions asked in industry-driven trials. Regulatory authorities have provided methodological guidance for industry-driven trials for the approval of new treatments, but such guidance is less clear for investigator-initiated trials. The European League Against Rheumatism (EULAR) task force for the update of the recommendations for the management of rheumatoid arthritis has critically looked at the methodological quality and conduct of many investigator-initiated trials, and has identified a number of concerns. In this Viewpoint paper, we highlight commonly encountered issues that are discussed using examples of well-known investigator-initiated trials. These issues cover three themes: (1) design choice (superiority vs non-inferiority designs); (2) statistical power and (3) convenience reporting. Since we acknowledge the importance of investigator-initiated research, we also propose a shortlist of points-to-consider when designing, performing and reporting investigator-initiated trials.
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A review of disease activity measures for psoriatic arthritis: what is the best approach?
Expert Rev Clin Immunol
PUBLISHED: 08-04-2014
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The measuring tools for disease activity of rheumatoid arthritis have long been adapted for assessing the disease activity of psoriatic arthritis (PsA), particularly as regards peripheral arthritis. However, because of the multifactorial aspects and multiple domains of PsA, such as axial and peripheral joints, skin and nails, enthesitis and dactylitis, must also be considered when measuring activity. After the introduction of biologic agents, it became clear that more objective measuring tools were needed to assess the varied aspects of disease activity, as well as the effect of treatment. Collaborations among international groups of rheumatologists and dermatologists have helped define key or core domains of PsA that were recommended for inclusion in clinical trials and potentially clinical practice. Groups such as the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis have tried to develop and validate new outcome measures in PsA. Several new composite measures for specific PsA have been recently developed. The domains, instruments and traditional and new composite measures for PsA are reviewed herein.
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Novel treatments with small molecules in psoriatic arthritis.
Curr Rheumatol Rep
PUBLISHED: 07-17-2014
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Current treatment options for patients with active psoriatic arthritis (PsA) include synthetic disease-modifying antirheumatic drugs and biologic agents. Propelled by increased understanding of immunopathogenesis of PsA, new therapeutic agents targeting different biologic pathways have been evaluated. This article discusses novel small-molecule, orally available treatments that are currently in clinical development for the treatment of psoriasis and PsA. This includes the phosphodiesterase 4 inhibitor apremilast and Janus kinase (JAK) inhibitors. Apremilast has demonstrated significant improvements in patients with moderate to severe psoriasis and PsA in phase II and III clinical trials and has recently been approved for the treatment of PsA. Tofacitinib, an oral inhibitor of JAK3, JAK1, and, to a lesser degree, JAK2, approved for the treatment of rheumatoid arthritis in several countries, has demonstrated positive results in psoriasis in phase II studies. Studies in PsA are ongoing. With these new developments, treatment options will continue to improve in the future.
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GRAPPA treatment recommendations: an update from the GRAPPA 2013 Annual Meeting.
J. Rheumatol.
PUBLISHED: 06-03-2014
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Psoriatic arthritis (PsA) is a chronic systemic inflammatory disorder characterized by the association of arthritis and periarticular inflammation in patients with psoriasis. In addition to a heterogeneous and variable clinical course, PsA is complex and multifaceted and may include prominent involvement in the peripheral and axial diarthrodial joints, the skin and nails, and in periarticular structures such as entheses. A central mission of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) is to develop guidelines, based upon the best scientific evidence, for the optimal treatment of patients with PsA. Guidelines were previously published in 2009 based on an evidence-based systematic review. Given important recent developments and robust ongoing research into the treatment of PsA, GRAPPA undertook to update the guidelines. Herein we outline the specific methods and procedures used both in the initial and the current evidence-based, systematic reviews of treatments for PsA. We also review the numerous discussions regarding how best to finalize and publish these new guidelines in 2014.
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Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics.
Arthritis Res. Ther.
PUBLISHED: 04-30-2014
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Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Currently, the relationship between pathogenic molecular drivers of disease in RA and therapeutic response is poorly understood.
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Benefits and risks of low-dose glucocorticoid treatment in the patient with rheumatoid arthritis.
Rheumatology (Oxford)
PUBLISHED: 04-10-2014
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Glucocorticosteroids (GCs) have been employed extensively for the treatment of rheumatoid arthritis (RA) and other autoimmune and systemic inflammatory disorders. Their use is supported by extensive literature and their utility is reflected in their incorporation into current treatment guidelines for RA and other conditions. Nevertheless, there is still some concern regarding the long-term use of GCs because of their potential for clinically important adverse events, particularly with an extended duration of treatment and the use of high doses. This article systematically reviews the efficacy for radiological and clinical outcomes for low-dose GCs (defined as ?10 mg/day prednisone equivalent) in the treatment of RA. Results reviewed indicated that low-dose GCs, usually administered in combination with synthetic DMARDs, most often MTX, significantly improve structural outcomes and decrease symptom severity in patients with RA. Safety data indicate that GC-associated adverse events are dose related, but still occur in patients receiving low doses of these agents. Concerns about side effects associated with GCs have prompted the development of new strategies aimed at improving safety without compromising efficacy. These include altering the structure of existing GCs and the development of delayed-release GC formulations so that drug delivery is timed to match greatest symptom severity. Optimal use of low-dose GCs has the potential to improve long-term outcomes for patients with RA.
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Effects of fostamatinib, an oral spleen tyrosine kinase inhibitor, in rheumatoid arthritis patients with an inadequate response to methotrexate: Results from a phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.
PUBLISHED: 04-08-2014
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Objective. This phase III, 52-week study (NCT01197521; OSKIRA-1) compared fostamatinib and placebo (for 24 weeks) in patients with active rheumatoid arthritis and an inadequate response to methotrexate (MTX) therapy. Methods. Patients taking MTX were randomized (1:1:1) to fostamatinib 100 mg bid for 52 weeks (Group A), 100 mg bid for 4 weeks then 150 mg qd (Group B), or placebo for 24 weeks then fostamatinib 100 mg bid (Group C). At Week 24, the co-primary end points were change from baseline in American College of Rheumatology 20% response rates (ACR20) and change in modified total Sharp van der Heijde score (mTSS). Results. 918 patients were randomized and received ?1 dose of study drug (placebo/fostamatinib); demographic/baseline characteristics were well balanced. Both fostamatinib regimens achieved a statistically significant difference in ACR20 at Week 24 versus placebo (49.0%, P < 0.001; 44.4%, P = 0.006 versus 34.2%), but failed to show a statistically significant difference in mTSS (P = 0.25; P = 0.17). The most common adverse events in patients in Groups A, B, and C were hypertension (15.8%, 15.1%, 3.9%) and diarrhea (13.9%, 15.1%, 3.9%). Elevated blood pressure (?140/90 mmHg) occurred in 44.2%, 41.6%, and 19.3% of patients at ?1 visit. Conclusion. Both fostamatinib regimens achieved statistically but not clinically significant improvements in ACR20 over placebo at 24 weeks and did not show a significant difference in mTSS. The overall level of response with fostamatinib was lower than observed in the phase ll program, but similar adverse events were reported. © 2014 American College of Rheumatology.
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Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor.
Ann. Rheum. Dis.
PUBLISHED: 03-04-2014
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Apremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy.
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Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey.
J. Am. Acad. Dermatol.
PUBLISHED: 02-24-2014
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Available psoriasis surveys offer valuable information about psoriasis and psoriatic arthritis (PsA), but are limited by methodology or enrollment requirements.
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Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout.
Arthritis Res. Ther.
PUBLISHED: 02-21-2014
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The efficacy of pegloticase, a polyethylene glycol (PEG)-conjugated mammalian recombinant uricase, approved for chronic refractory gout, can be limited by the development of antibodies (Ab). Analyses from 2 replicate, 6-month, randomized controlled trials were performed to characterize Ab responses to pegloticase.
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Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, dou
Ann. Rheum. Dis.
PUBLISHED: 01-30-2014
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Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents.
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Clinical, Functional, and Radiographic Implications of Time to Treatment Response in Patients With Early Rheumatoid Arthritis: a Posthoc Analysis of the PREMIER Study.
J. Rheumatol.
PUBLISHED: 12-01-2013
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Rheumatoid arthritis (RA) treatment recommendations suggest target attainment within the first 3 months of therapy, yet delayed clinical responses can occur. This analysis assessed the longterm clinical, functional, and radiographic outcomes associated with delayed responses to methotrexate (MTX) monotherapy or to the combination of adalimumab (ADA) + MTX.
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Longterm Effect of Delaying Combination Therapy with Tumor Necrosis Factor Inhibitor in Patients with Aggressive Early Rheumatoid Arthritis: 10-year Efficacy and Safety of Adalimumab from the Randomized Controlled PREMIER Trial with Open-label Extension.
J. Rheumatol.
PUBLISHED: 11-15-2013
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To evaluate the longterm safety of adalimumab administered with or without methotrexate (MTX) and compare the efficacy of combination therapy initialization to adalimumab or MTX monotherapy initialization during the open-label extension (OLE) of the PREMIER trial (ClinicalTrials.gov Identifier:NCT00195663).
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Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial.
Lancet
PUBLISHED: 10-26-2013
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Biological agents offer good control of rheumatoid arthritis, but the long-term benefits of achieving low disease activity with a biological agent plus methotrexate or methotrexate alone are unclear. The OPTIMA trial assessed different treatment adjustment strategies in patients with early rheumatoid arthritis attaining (or not) stable low disease activity with adalimumab plus methotrexate or methotrexate monotherapy.
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Adverse effects of golimumab in the treatment of rheumatologic diseases.
Expert Opin Drug Saf
PUBLISHED: 08-28-2013
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Introduction: A number of new biological immune modulators have become available as treatments for inflammatory diseases over the past two decades. Most prominent among them are TNF-? inhibitors (TNFi) which have been available in the clinic since the late 1990s. TNFi have demonstrated efficacy in various rheumatologic diseases as well as in inflammatory bowel disease and psoriasis. Golimumab is one of the most recently introduced TNFi. Areas covered: Although golimumab is generally well tolerated, as is the case with other TNFi and indeed with most of the marketed immunomodulatory drugs, potential adverse events may be associated with its use. Herein, we the potential adverse effects associated with golimumab therapy are reviewed. Adverse effects are divided into target-related and agent-related categories. Expert opinion: Golimumab has been demonstrated to be generally safe and well tolerated. Its safety profile seems to be very comparable to the other available TNFi. Long-term studies of golimumab and other TNFi will help establish the durability of response to golimumab as well as identify any potential delayed or cumulative adverse effects.
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Use of data from multiple registries in studying biologic discontinuation: challenges and opportunities.
Clin. Exp. Rheumatol.
PUBLISHED: 08-22-2013
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Many studies have been conducted concerning discontinuation of biologic disease-modifying anti-rheumatic drugs (DMARD), but mainly in trial settings which result in limited generalisability. Registry studies can complement the current literature of biologic DMARD discontinuation by providing more generalisable information. However, it may be necessary to combine registries to increase power and provide more diverse patient populations. This increased power could provide us information about risk and benefits of discontinuing biologic DMARD in typical clinical practice. However, use of multiple registries is not without challenges. In this review, we discuss the challenges to combining data across multiple registries, focusing on biologic discontinuation as an example. Challenges include: 1) generalizability of each registry; 2) new versus prevalent users designs; 3) outcome definitions; 4) different health care systems; 5) different follow up intervals; and 6) data harmonisation. The first three apply to each registry, and the last three apply to combining multiple registries. This review describes these challenges, corresponding solutions, and potential future opportunities.
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Prevalence and incidence rates of psoriatic arthritis in central Norway: data from the Nord-Trondelag Health Study (HUNT).
Ann. Rheum. Dis.
PUBLISHED: 08-22-2013
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A wide range in the prevalence (<0.01-0.25%) and incidence (0.5-23.1/100 000) of psoriatic arthritis (PsA) is reported. The main objective of this study was to examine the prevalence and incidence of PsA in central Norway.
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The when and how of biologic agent withdrawal in rheumatoid arthritis: learning from large randomised controlled trials.
Clin. Exp. Rheumatol.
PUBLISHED: 08-19-2013
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There has been great interest lately concerning the possibility that in the treatment of rheumatoid arthritis, biologic agents might be withdrawn for patients who achieve desirable targets, such as low disease activity or remission. While there are a number of reasons why such a treatment paradigm might be desirable, there is a paucity of relevant data at present to guide clinicians about embarking on such a treatment change. Data is starting to emerge, much of it from controlled trials, that can provide some guidance as to which patients might be the best candidates for such an approach. These data will provide answers to the key questions that remain concerning this important potential paradigm shift in the treatment of rheumatoid arthritis as well as other systemic inflammatory autoimmune diseases.
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Treat to Target: A Proposed New Paradigm for the Management of Crohns Disease.
Clin. Gastroenterol. Hepatol.
PUBLISHED: 07-04-2013
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The traditional management of Crohns disease, which is based on progressive, step-wise treatment intensification with re-evaluation of response according to symptoms, does not improve long-term outcomes of Crohns disease and places patients at risk for bowel damage. The introduction of novel therapies and the development of new approaches to treatment in rheumatoid arthritis led to better outcomes for patients. Prominent among these is a "treat to target" strategy that is based on regular assessment of disease activity by using objective clinical and biological outcome measures and the subsequent adjustment of treatments. This approach is complementary to the concept of early intervention in high-risk patients. This review evaluates current literature on this topic and proposes a definition for the concept of treating to targets for Crohns disease.
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Psoriatic arthritis: current therapy and future directions.
Expert Opin Pharmacother
PUBLISHED: 07-02-2013
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Psoriatic arthritis (PsA) once regarded as an auto-inflammatory arthritis that involves the skin is proving to be more complex with a different driver of disease process compared to rheumatoid arthritis. As growing differences emerge between PsA and rheumatoid arthritis so have the experiences and responses to therapeutics used in both disease processes.
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Clinical, functional, and radiographic benefits of longterm adalimumab plus methotrexate: final 10-year data in longstanding rheumatoid arthritis.
J. Rheumatol.
PUBLISHED: 07-01-2013
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To examine the longterm effectiveness and safety of adalimumab in patients with longstanding rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX), and to assess the effect of a 1-year delay in initiation of combination therapy.
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Hand bone loss in patients with psoriatic arthritis: posthoc analysis of IMPACT II data comparing infliximab and placebo.
J. Rheumatol.
PUBLISHED: 06-15-2013
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In rheumatoid arthritis (RA), anti-tumor necrosis factor (anti-TNF) treatment is shown to reduce but not to arrest the rate of hand bone loss. This has not been assessed in psoriatic arthritis (PsA). Our objective was to examine changes in cortical hand bone density in patients with PsA treated with placebo or infliximab (IFX).
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Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial.
Lancet
PUBLISHED: 06-13-2013
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Many patients with psoriasis develop psoriatic arthritis, a chronic inflammatory disease that afflicts peripheral synovial, axial, and entheseal structures. The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis. We did a randomised, placebo-controlled, phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis.
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Biologic discontinuation studies: a systematic review of methods.
Ann. Rheum. Dis.
PUBLISHED: 05-30-2013
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OBJECTIVES: We conducted a systematic review to assess the design and failure definition in studies of biologic discontinuation in rheumatoid arthritis (RA). METHODS: We found 403 studies on PubMed, and included nine published papers and five abstracts from scientific meetings. We used a structured extraction form to collect information regarding study design and outcome (failure) definition. RESULTS: Three types of studies were found: randomised controlled trials, long-term extension studies of clinical trials and prospective discontinuation studies. The largest study had 196 subjects in the discontinuation arm. Most studies allowed concomitant use of non-biologic drugs at biologic discontinuation. Heterogeneity was also found in the failure definition. Although all studies used measures of disease activity, the threshold for failure and the time point of assessment differed among studies. Few studies incorporated changing use of non-biologic drugs or glucocorticoids into the failure definition. CONCLUSIONS: Although many studies have examined the outcome of biologic discontinuation, they have all been relatively small. Typical practice studies from registries may add important information but will likely need to rely on a broader failure definition.
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Treatment of spondyloarthropathy: the potential for agents other than TNF inhibitors.
Curr Opin Rheumatol
PUBLISHED: 05-18-2013
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Inhibitors of tumor necrosis factor (TNF) have demonstrated dramatic clinical efficacy in patients with spondyloarthropathy (SpA). However, not all patients respond, and some patients who initially improve, subsequently lose response. Therefore, there is still an unmet clinical need for additional therapies. Herein we describe the recent data on newer treatments for SpA patients.
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Proceedings of the 2013 Rheumatology Winter Clinical Symposia.
Semin. Arthritis Rheum.
PUBLISHED: 04-02-2013
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Advances in rheumatology occur at a rapid pace and staying abreast of important changes is a challenge for all. Both novel drug development and enhanced understanding of conventional or historic therapies have molded current day rheumatologic practice. Rheumatology has led the way in the use of outcome measures and imaging modalities in common disorders like rheumatoid arthritis, osteoarthritis, and gout. The expertise of the rheumatologist has widened such that knowledge of economics, legal issues, related disorders and extraarticular disease is essential. In February 2013, the 6th annual Rheumatology Winter Clinical Symposium was held. At this meeting, faculty and participants held discussions and exchanged knowledge about new scientific data and how it may impact the care of rheumatology patients. Excerpts from some of the lectures from the Rheumatology Winter Clinical Symposium 2013 are included in this review. These and other presentations can be viewed in their entirety at http://www.r-w-c-s.com.
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Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial.
Lancet
PUBLISHED: 03-18-2013
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Roughly a third of patients with rheumatoid arthritis treated with biological treatments receive them as monotherapy. Tocilizumab--an inhibitor of interleukin 6 receptor signalling--has been studied as monotherapy in several clinical trials. We assessed the efficacy and safety of tocilizumab monotherapy compared with adalimumab monotherapy for patients with rheumatoid arthritis.
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The problem of choice: current biologic agents and future prospects in RA.
Nat Rev Rheumatol
PUBLISHED: 02-19-2013
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The introduction of biologic agents to clinical practice has had a major bearing on the treatment of patients with chronic inflammatory diseases such as rheumatoid arthritis. These drugs have the potential to improve the outcome of disease and the quality of life for patients. However, clinical criteria alone are inadequate for determining which therapy is most appropriate for an individual patient. Furthermore, why a particular drug is effective in a particular patient, or indeed in any patient, but is ineffective for other individuals, is often unknown. In this Review, we provide an overview of biologic therapies currently available for patients with rheumatoid arthritis, and discuss why certain immunological regulators represent potential targets for intervention. Current agents can be clustered into three major types: cytokine blockers, lymphocyte-targeting agents, and small-molecule inhibitors of signal transduction pathways. We differentiate among the modes of action of each of these types of therapy and consider the challenges associated with their use in clinical practice.
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Early effects of tocilizumab in the treatment of moderate to severe active rheumatoid arthritis: a one-week sub-study of a randomised controlled trial (Rapid Onset and Systemic Efficacy [ROSE] Study).
Clin. Exp. Rheumatol.
PUBLISHED: 01-10-2013
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Tocilizumab has demonstrated efficacy in managing rheumatoid arthritis (RA) from week 2 onward. This sub-study assessed effects of tocilizumab plus disease-modifying anti-rheumatic drugs (DMARDs) during the first week of therapy.
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Predicting low disease activity and remission using early treatment response to antitumour necrosis factor therapy in patients with rheumatoid arthritis: exploratory analyses from the TEMPO trial.
Ann. Rheum. Dis.
PUBLISHED: 10-13-2011
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To derive and validate decision trees to categorise rheumatoid arthritis (RA) patients 12 weeks after starting etanercept with or without methotrexate into three groups: patients predicted to achieve low disease activity (LDA) at 1 year; patients predicted not to achieve LDA at 1 year and patients who needed additional time on therapy to be categorised.
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Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis and a previous inadequate response to disease-modifying antirheumatic drugs: the ROSE study.
Ann. Rheum. Dis.
PUBLISHED: 09-26-2011
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To evaluate efficacy of tocilizumab in US patients with moderate to severe active rheumatoid arthritis (RA) and inadequate clinical response to disease-modifying antirheumatic drugs (DMARD). Safety-related outcomes were also analysed.
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Biologic modulators in allergic and autoinflammatory diseases.
Curr Opin Allergy Clin Immunol
PUBLISHED: 06-11-2011
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The advent of molecular techniques has resulted in the ability to tailor medications to specific protein targets. This review will emphasize several biological therapies, specifically directed toward cytokine receptors and inhibitors, and their role in the treatment of atopic and autoinflammatory diseases.
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The role of monoclonal antibodies in the treatment of severe asthma.
Ther Adv Respir Dis
PUBLISHED: 03-10-2011
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A number of therapeutic agents are available for the treatment of asthma, including inhaled corticosteroids, long- and short-acting beta-agonists, leukotriene-modifying agents, long- and short-acting anticholinergic agents, chromones, theophylline, allergen immunotherapy, and oral corticosteroid therapy. All available therapies, despite their proven efficacy, are purely symptomatic including the topical steroids. This issue has led to the development of several biologic agents to aid in asthma management and to potentially alter the course of the disease by interfering with specific aspects of inflammation which may modify remodeling in the airways. Monoclonal antibodies have offered a class of therapeutic agents that enhance treatment options for patients with moderate-to-severe persistent asthma. As such, this article provides an overview of present and future monoclonal antibody therapies for the treatment of patients with severe asthma.
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Minimally important differences of the gout impact scale in a randomized controlled trial.
Rheumatology (Oxford)
PUBLISHED: 03-03-2011
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The Gout Impact Scale (GIS) is a gout-specific quality of life instrument that assesses impact of gout during an attack and impact of overall gout. The GIS has five scales and each is scored from 0 to 100 (worse health). Our objective was to assess minimally important differences (MIDs) for the GIS administered in a randomized controlled trial (RCT) assessing rilonacept vs placebo for prevention of gout flares during initiation of allopurinol therapy.
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Adalimumab reduces hand bone loss in rheumatoid arthritis independent of clinical response: subanalysis of the PREMIER study.
BMC Musculoskelet Disord
PUBLISHED: 02-27-2011
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Anti-TNF therapy has been shown to reduce radiographic joint damage in rheumatoid arthritis (RA) independent of clinical response. This has previously not been examined for periarticular bone loss, the other characteristic feature of bone involvement in RA.The objective of this study was to examine if treatment with the TNF-? inhibitor adalimumab also could reduce periarticular bone loss in RA patients independent of disease activity.
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Clinical consequences of delayed addition of adalimumab to methotrexate therapy over 5 years in patients with rheumatoid arthritis.
J. Rheumatol.
PUBLISHED: 02-01-2011
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This Year 5 analysis of an open-label extension (OLE) study assessed radiographic progression, clinical efficacy, and safety of adalimumab with concomitant methotrexate (MTX) for patients with active rheumatoid arthritis.
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An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: a three-month randomized, placebo-controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents.
Arthritis Rheum.
PUBLISHED: 02-01-2011
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To assess the efficacy and safety of R788 (fostamatinib disodium), an inhibitor of spleen tyrosine kinase (Syk), in patients with active rheumatoid arthritis (RA) that did not respond to biologic therapies.
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Inhibition of IL6 in rheumatoid arthritis and juvenile idiopathic arthritis.
Exp. Cell Res.
PUBLISHED: 01-04-2011
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A number of clinical trials have been done to investigate the role of interleukin-6 (IL-6) as a potential therapeutic target in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Most of the data testing this comes from trials of the humanized anti Il-6 receptor antibody tocilizumab. Results from clinical trials worldwide have been promising so far. Additional study will define the ultimate role of tocilizumab and Il6 inhibitors in the treatment paradigms for RA and JIA.
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CXCL13: a novel biomarker of B-cell return following rituximab treatment and synovitis in patients with rheumatoid arthritis.
Rheumatology (Oxford)
PUBLISHED: 11-23-2010
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The B-cell chemokine, CXCL13, is a proposed serum biomarker of synovitis in RA. Its behaviour in the context of B-cell depletion therapy and reconstitution was studied during treatment of RA with rituximab.
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Disease activity, physical function, and radiographic progression after longterm therapy with adalimumab plus methotrexate: 5-year results of PREMIER.
J. Rheumatol.
PUBLISHED: 10-01-2010
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To evaluate the efficacy and safety of initial combination treatment with adalimumab (ADA) and methotrexate (MTX) versus monotherapy with ADA or MTX during an open-label extension of PREMIER.
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An oral spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis.
N. Engl. J. Med.
PUBLISHED: 10-01-2010
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Spleen tyrosine kinase (Syk) is an important modulator of immune signaling. The objective of this phase 2 study was to evaluate the efficacy and safety of R788, an oral inhibitor of Syk, in patients with active rheumatoid arthritis despite methotrexate therapy.
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Effect of ustekinumab on physical function and health-related quality of life in patients with psoriatic arthritis: a randomized, placebo-controlled, phase II trial.
Curr Med Res Opin
PUBLISHED: 09-14-2010
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To use data from a phase II clinical trial to evaluate the effect of ustekinumab, a human immunoglobulin monoclonal antibody that binds with high affinity to the shared p40 subunit of human interleukins-12 and -23, on physical disability and health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA).
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Predictors of doctor-rated and patient-rated gout severity: gout impact scales improve assessment.
J Eval Clin Pract
PUBLISHED: 08-15-2010
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RatIONALE, AIMS AND OBJECTIVES: Our objective was to describe the factors associated with doctor-rated and patient-rated gout severity to explain how doctor assessment involving patient-reported outcomes can improve the clinical management of gout.
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A pilot study of rituximab in immune-mediated inner ear disease.
Audiol. Neurootol.
PUBLISHED: 07-13-2010
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Immune-mediated inner ear disease (IMED) is a cause of rapidly progressive auditory dysfunction. Patients are often responsive to high-dose corticosteroids and the disease is believed to be mediated by an antibody to inner ear proteins. To date, no therapies have proven effective as corticosteroid-sparing agents. Rituximab is a monoclonal antibody that depletes B cells, resulting in a reduction in autoantibody production. For that reason, rituximab was evaluated in a small pilot study in patients with IMED to see if there was a signal suggesting benefit. In all, 5/7 patients met the primary endpoint of an improvement in pure tone average (500-3000 Hz) by 10 dB in at least one ear, or an improvement in word identification score by at least 12% at 24 weeks, both relative to screening precorticosteroid values after 1 course of treatment. No significant adverse events were reported. The results of this study suggest further evaluation of rituximab as a treatment for IMED is indicated.
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Application of the DAREA/DAPSA score for assessment of disease activity in psoriatic arthritis.
Ann. Rheum. Dis.
PUBLISHED: 06-04-2010
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Instruments for measuring disease activity in psoriatic arthritis (PsA) are not yet firmly established, and most of the currently employed ones have been derived for rheumatoid arthritis. Some of these instruments are based on 28 joint counts, which do not capture joints frequently affected in PsA. Therefore, the reliability and validity of DAREA (for Disease Activity index for REactive Arthritis), which was originally developed for reactive arthritis and employs a 66/68 joint count, was tested in patients with PsA.
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Risk of elevated liver enzymes associated with TNF inhibitor utilisation in patients with rheumatoid arthritis.
Ann. Rheum. Dis.
PUBLISHED: 05-06-2010
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Liver function test (LFT) elevations are reported with the use of tumour necrosis factor inhibitors (TNF-Is). The aim of this study was to compare LFT elevations in patients with rheumatoid arthritis receiving adalimumab (ADA), etanercept (ETN) or infliximab (INF) enrolled in the Consortium of Rheumatology Researchers of North America from October 2001 to March 2007.
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Treatment of psoriatic arthritis with biological agents.
Semin Cutan Med Surg
PUBLISHED: 05-01-2010
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Psoriatic arthritis (PsA) is an inflammatory arthritis that occurs in individuals with psoriasis. The primary goals in the treatment of PsA are reduction of pain; improvement in the other signs and symptoms of disease, including skin and nail involvement; optimization of functional capacity and quality of life; and inhibition of the progression of joint damage. These goals should be achieved while minimizing potential toxicities from treatment. The management of PsA should simultaneously target arthritis, skin disease, and other manifestations of PsA, including involvement of the axial skeleton, dactylitis, enthesitis, and eye inflammation. In this respect targeted biological agents, primarily tumor necrosis factor inhibitors, have emerged as generally well tolerated and highly effective alternatives to traditional disease modifying antirheumatic drugs. Herein we review the evidence regarding the treatment of PsA arthritis with biological agents.
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Gout disease-specific quality of life and the association with gout characteristics.
Patient Relat Outcome Meas
PUBLISHED: 03-01-2010
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PURPOSE: Assess the association of gout characteristics with health-related quality of life (HRQoL) using a new gout-specific HRQoL instrument, the Gout Impact Scale (GIS). PATIENTS AND METHODS: Gout patients completed the GIS (five scales [0-100 score each] representing impact of gout overall [three scales] and during an attack [two scales]) and other questions describing recent gout attacks, treatment, gout history, comorbidities, and demographics. Physicians confirmed gout diagnosis, presence of tophi, and most recent serum uric acid (sUA) level. Relationships between gout characteristics and GIS scores were examined using analysis of variance and correlation analyses. RESULTS: The majority of patients were male (90.2%) with a mean age of 62.2 (±11.8) years. Approximately one-half (49.7%) reported ?3 gout attacks in the past year and the majority (57.9%) reported experiencing gout-related pain between attacks. Patients had appreciable concern about their gout ("gout concern overall" scale, 63.1 ± 28.0) but believed their treatment was adequate ("unmet gout treatment need" scale (38.2 ± 21.4) below scale mid-point). Significantly worse GIS scores were associated with increasing attack frequency and greater amount of time with pain between attacks (most scales, P < 0.001). Common objective measures such as sUA level, presence of tophi and the number of joints involved in a typical attack did not appear to be good indicators of the impact of gout on the patients HRQoL. CONCLUSION: Attack frequency and gout pain between attacks were important correlates of patients ratings of gout impact on their HRQoL. Further studies are needed to determine the minimal important difference for each GIS scale and interpret our results relative to other patient populations with gout.
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Standardization of joint examination technique leads to a significant decrease in variability among different examiners.
J. Rheumatol.
PUBLISHED: 02-15-2010
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To reduce the amount of variability among assessors, we conducted joint examination standardization seminars in conjunction with multicenter clinical trials for patients with rheumatoid arthritis (RA). The examination techniques used were based on the recommendations of the European League Against Rheumatism (EULAR).
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Patient-derived joint counts are a potential alternative for determining Disease Activity Score.
J. Rheumatol.
PUBLISHED: 02-15-2010
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To investigate the correlation between the Disease Activity Score using a 28-joint count (DAS28) based on physician-derived joint counts and the DAS28 based on patient-derived joint counts (Pt-DAS28) in rheumatoid arthritis (RA).
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Biomarkers in psoriasis and psoriatic arthritis: GRAPPA 2008.
J. Rheumatol.
PUBLISHED: 02-12-2010
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Biomarkers can provide valuable insights into disease susceptibility and natural history and may serve as surrogate endpoints for a variety of different outcomes. At the 2008 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), members were updated on the development of biomarkers in psoriatic arthritis (PsA). Plenary presentations included a translational approach to biomarker development (Christopher Ritchlin, University of Rochester, NY, USA), biomarkers for psoriasis (Abrar Qureshi, Harvard Medical School, MA, USA), new data on biomarkers for damage in PsA (Kurt de Vlam, University Hospitals Leuven, Belgium), and design considerations for a longitudinal study of joint damage being undertaken under the OMERACT umbrella with colleagues working on rheumatoid arthritis and ankylosing spondylitis (Costantino Pitzalis, Barts and the London School of Medicine, London, UK; Oliver FitzGerald, St. Vincents Hospital, Dublin, Ireland). At the conclusion of this session, the meeting attendees discussed specific design issues of the proposed longitudinal study, including study duration, disease process core domains, and the instruments to be used in recording enthesitis, dactylitis, nail involvement, quality of life and structural damage. The appearance of new therapeutic options in PsA raises the need for sensitive biomarkers for both disease activity and outcome.
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Composite measures in psoriatic arthritis: GRAPPA 2008.
J. Rheumatol.
PUBLISHED: 02-12-2010
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At the 2008 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) in Leeds, UK, members discussed the value and current status of composite measures for the assessment of psoriatic arthritis (PsA). In plenary presentations, examples of composite measures developed for rheumatoid arthritis (RA) and ankylosing spondylitis (AS) were reviewed, followed by a presentation of the assessment of disease activity in systemic lupus erythematosus. Three recently devised composite methods of assessing activity or response in PsA also were presented. Considerable discussion followed in breakout groups, and members agreed that a new composite measure specifically for PsA is necessary. The composite measure should include components that encompass the spectrum of psoriatic disease, i.e., in addition to assessment of peripheral joints, it should include assessment of sacroiliitis, spondylitis, enthesitis, and dactylitis, as well as skin and nail disease.
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Imaging in psoriasis and psoriatic arthritis: GRAPPA 2008.
J. Rheumatol.
PUBLISHED: 02-12-2010
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At the 2008 meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), the primary focus of the imaging session was the enthesis. Presentations from Dennis McGonagle (Leeds, UK), Richard Hodgson (Leeds, UK), and Paolo Gisondi (Verona, Italy) elaborated on this theme and prepared the meeting attendees for group discussions of further work in this area. Imaging, notably magnetic resonance imaging (MRI) and ultrasonography, provides evidence of pathological change at the enthesis in psoriatic arthritis (PsA). Further, imaging abnormalities are found at sites that are asymptomatic in both PsA and psoriasis. The role of newer imaging modalities, such as ultra-short echo time (UTE) MRI, is promising but remains to be fully elucidated. The implication of these findings in relation to subclinical and predisease status is intriguing and requires further study in longitudinal studies. Further work is also required to examine the proposed common biomechanical basis between joint and skin, the mechanism of the resulting inflammation, and how these mechanisms differ from those seen in rheumatoid arthritis.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.