Rheumatoid Arthritis: Emery P

Emery P. · Academic Unit of Musculoskeletal Disease, Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds LS7 4SA. · BMJ. · Pubmed #16424492 links to  free full text

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Conaghan PG, McQueen FM, Peterfy CG, Lassere MN, Ejbjerg B, Bird P, O'Connor PJ, Haavardsholm E, Edmonds JP, Emery P, Genant HK, Ostergaard M, Anonymous00379. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · J Rheumatol. · Pubmed #16331788 No free full text.

Abstract: Magnetic resonance imaging (MRI) has now been used extensively in cross-sectional and observational studies as well as in controlled clinical trials to assess disease activity and joint damage in rheumatoid arthritis (RA). MRI measurements or scores for erosions, bone edema, and synovitis have been developed and validated by several groups. The OMERACT criteria require that outcome measures demonstrate adequate validity, discriminative power, and feasibility if they are to be useful in clinical trials. Specific performance targets for these criteria depend on the scientific, regulatory, logistical, and financial context of the study in question. We review the extent to which MRI assessments of joint erosion, bone edema, and synovitis fulfil these criteria, particularly as they relate to proof-of-concept RA clinical trials.

Quinn MA, Emery P. · Academic Unit of Musculoskeletal Disease, Department of Rheumatology, Chapel Allerton Hospital, 2nd Floor, Chapel Town Road, Leeds LS7 4SA, UK. · Rheum Dis Clin North Am. · Pubmed #16287596 No free full text.

Abstract: The potential for disproportionately altering outcome in the early stages of rheumatoid arthritis (RA) was first hypothesized in the early 1990s. This window of opportunity hypothesis for therapeutic intervention in RA is based on the existence of a time frame within which there is a potential for a greater response to therapy, resulting in sustained benefits or, perhaps most important, a chance of cure. Given the persistent, progressive, damaging, inflammatory nature of RA, this approach to altering outcome in the early stages seems attractive.

Haugeberg G, Emery P. · Department of Rheumatology, Sørlandet Hospital, Kristiansand, Norway. · Rheum Dis Clin North Am. · Pubmed #16287593 No free full text.

Abstract: New research has revealed common pathophysiologic and cellular mechanisms behind the development of osteoporosis and joint damage in rheumatoid arthritis (RA). Because osteoporosis is a direct consequence of the inflammatory disease process, bone mass measurements in principle could be an outcome marker of inflammation, of damage, and of response to therapeutic intervention. Several devices have been developed for quantitative bone mass assessment including dual energy x-ray absorptiometry (DXA), which is considered the reference standard. This article based on current data and understanding discusses the use of DXA as a diagnostic and assessment tool especially in early RA.

Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Bijlsma JW, Dougados M, Emery P, Keystone EC, Klareskog L, Mease PJ. · 1000 Veteran Avenue Rehabilitation Centre, Room 32-59, Los Angeles, CA 90024, USA. · Ann Rheum Dis. · Pubmed #16239380 links to  free full text

This publication has no abstract.

Mackie SL, Vital EM, Ponchel F, Emery P. · Academic Unit of Musculoskeletal Disease, University of Leeds, Chapel Allerton Hospital, Leeds, LS7 4SA, UK. · Curr Rheumatol Rep. · Pubmed #16174492 No free full text.

Abstract: There is substantial evidence that rheumatoid arthritis is an autoimmune disease in which T cells are aberrantly activated. Existing therapies, including anti-tumor necrosis factor therapies, are successful for many patients, but the goal of lasting remission still frequently proves elusive. One novel therapeutic strategy is the blockade of T-cell co-stimulation to modulate T-cell activation. The first co-stimulation blocker to reach clinical trials is abatacept (CTLA4Ig). Initial abatacept trials have shown promise and further phase III trials are underway.

Kalden JR, Antoni C, Alvaro-Gracia JM, Combe B, Emery P, Kremer JM, Strand CV, Van Riel P, Smolen JS. · Medizinische Klinik III, Institute for Clinical Immunology, Erlangen, Germany. · J Rheumatol. · Pubmed #16078347 No free full text.

Abstract: An Expert Panel Meeting was held in May 2004 to assess experience with combination therapy with leflunomide and biological agents in the treatment of rheumatoid arthritis (RA), to identify both optimal use of such combinations and precautions for use. Eleven published prospective or retrospective studies were reviewed, principally evaluating combination of leflunomide with infliximab, as well as patient registry data. Available data suggest that combination therapies are more efficacious than monotherapies, reflecting the complementarity of mechanisms of action. Information on side effects remains contradictory, and tolerability of these combinations may vary between different patient groups. In some studies, tolerability is equivalent to that seen with monotherapy; in others a high rate of adverse events has led to frequent treatment discontinuation. Dermatological reactions may be a specific side effect of these combination therapies. Combination therapy is considered justified for treatment of patients diagnosed early who are at risk for rapid progression and for patients who fail to respond to monotherapy. The majority of participants favored adding biological agents to a previously established leflunomide monotherapy rather than starting both treatments simultaneously. On the other hand, combination therapy should be considered with caution in patients with a history of treatment failure, with hepatic comorbidity, or with other autoimmune disease, and in immunocompromised patients. When considering initiation of combination therapy, it is important to provide full information to the patient on the potential benefits and risks of such treatment and to integrate patients as far as possible into the decision-making process.

Emery P. · Leeds Teaching Hospital Trust, University of Leeds, Leeds, UK. · Drugs Today (Barc). · Pubmed #15883612 No free full text.

Abstract: Adalimumab (Humira) is the first fully human monoclonal anti-tumor necrosis factor (TNF) antibody available. Similar to the other TNF-alpha blockers, adalimumab has been shown to effectively reduce the symptoms and signs of rheumatoid arthritis and prevent the progression of erosive joint changes seen on radiological examination, which would lead to disabling joint damage. Clinical guidelines recommend the use of TNF blockers, specifically etanercept and infliximab (the only two available when the guidelines were issued) as treatment options for adults with rheumatoid arthritis who continue to have clinically active disease that has not responded adequately to two conventional disease-modifying antirheumatic drugs (DMARDs). The clinical results available using adalimumab, and summarized in this review, reveal a clinical profile similar to etanercept and infliximab, achieving similarly high response rates, suppression of joint damage, and improvements in quality of life and disability, together with a good safety profile. Being a fully human monoclonal antibody, adalimumab may induce less antigenicity than these other agents, which might also be advantageous in maintaining the level of effectiveness. However, direct comparisons in controlled, long-term trials are needed to draw conclusions about which agent to try first in the sequence of DMARDs considered for patients.

Keen HI, Emery P. · Academic Unit of Musculoskeletal Disease, Department of Rheumatology, Leeds General Infirmary, Leeds, UK. · Curr Opin Rheumatol. · Pubmed #15838237 No free full text.

Abstract: PURPOSE OF REVIEW: Rheumatoid arthritis is a chronic systemic and progressive inflammatory disorder of the synovium characterised by destruction of bone and cartilage. It is associated with significant morbidity and economic costs. Recent advances have shown that early diagnosis and timely, intensive therapy of rheumatoid arthritis can modify disease outcomes. RECENT FINDINGS: Current investigations into the role of ultrasonography and magnetic resonance imaging in early rheumatoid arthritis suggest these modalities will provide information to assist in the early diagnosis of rheumatoid arthritis, identify poor prognostic factors, and aid in the monitoring of response to therapy. New developments in pharmacologic therapy, particularly the development of biologic agents, allow better disease control than was previously achievable, and the early application of these drugs in combination with conventional disease-modifying antirheumatic drugs seems to produce the best outcomes. SUMMARY: The application of novel imaging techniques will aid the target application of biologic therapy within the window of opportunity and aid in the monitoring of response to therapy. This is likely to significantly decrease the rate of structural damage and offers hope of a future when the normal outcome for rheumatoid arthritis will be remission.

Bird P, Conaghan P, Ejbjerg B, McQueen F, Lassere M, Peterfy C, Edmonds J, Shnier R, O'Connor P, Haavardsholm E, Emery P, Genant H, Østergaard M. · Department of Rheumatology, St. George Hospital, University of NSW, Sydney, Australia. · Ann Rheum Dis. · Pubmed #15647422 links to  free full text

Abstract: Based on a previously developed rheumatoid arthritis MRI scoring system (OMERACT 2002 RAMRIS), the development team agreed which joints, MRI features, MRI sequences, and image planes would best illustrate the scoring system in an atlas. After collecting representative examples for all grades for each abnormality (synovitis, bone oedema, and bone erosion), the team met for a three day period to review the images and choose by consensus the most illustrative set for each feature, site, and grade. A predefined subset of images (for example, for erosion--all coronal slices through the bone) was extracted. These images were then re-read by the group at a different time point to confirm the scores originally assigned. Finally, all selected images were photographed and formatted by one centre and distributed to all readers for final approval.

Quinn MA, Emery P. · Academic Unit of Musculoskeletal Disease, Department of Rheumatology, Leeds General Infirmary, 1st Floor, Great George Street, Leeds LS13EX, UK. · Best Pract Res Clin Rheumatol. · Pubmed #15588968 No free full text.

Abstract: Landmark studies published in the 1980s were the first to reveal the long-term consequences of rheumatoid arthritis (RA). Instead of the benign outcomes previously reported from early population studies, disability, deformity and excess mortality were evident. At this time, the conventional pyramid approach was the standard for therapeutic intervention. Patients were initially treated with non-steroidal anti-inflammatory drug with rest and splinting a approach. Disease-modifying anti-rheumatic drugs and corticosteroids were reserved for patients with joint damage and disability, who had 'earned their treatment' and the perceived risk of toxicity. Thus irreversible damage and disability occurred prior to effective therapy being instituted, with the consequences of poor outcomes. The late 1980s saw the introduction of the concept of early intervention in RA and, shortly after, the introduction of specialist clinics for early assessment of patients with inflammatory arthritis (IA), so-called 'early arthritis clinics' (EACs). Such clinics, initially in large research units, targeted patients with early RA or IA with the potential to evolve to RA, with the aim of early case definition and treatment. After all, the common sense approach to treatment of a chronic inflammatory, destructive condition would be to treat it effectively from its onset, prior to the development of irreversible damage. The detailed documentation undertaken in these clinics subsequently provided much information regarding persistence and prognosis in early IA. Since their initial introduction, EACs have become commonplace, not only in academic units, but also kas part of clinical service provision in many institutions. This review details what an EAC is, who should be referred and when, and the benefits and potential future benefits of their introduction.

Brown AK, Wakefield RJ, Conaghan PG, Karim Z, O'Connor PJ, Emery P. · Academic Unit of Musculoskeletal Disease, Department of Rheumatology, University of Leeds, Leeds General Infirmary, UK. · Clin Exp Rheumatol. · Pubmed #15552510 No free full text.

Abstract: Imaging techniques such as musculoskeletal ultrasonography (MUS) and magnetic resonance imaging (MRI) are playing an increasingly important role in the assessment of patients with inflammatory arthritis. Such modalities are now used routinely in the evaluation of joint, tendon and soft tissue inflammation and bone damage in many early arthritis clinics. They have the ability to directly visualise, characterise and quantify the earliest inflammatory changes and have proved not only to be useful additional complimentary clinical tools to improve the speed and accuracy of diagnosis, direct appropriate treatment, monitor response to therapy, measure disease progression and outcome but also continue to contribute to our understanding of disease pathogenesis. These imaging methods may therefore offer a significant advantage as they endorse the principles of early diagnosis and optimal targeted therapy essential to providing the most favourable long term outcome for patients with inflammatory arthritis. This article reviews the current evidence supporting the role of MUS and MRI in the assessment of patients with inflammatory arthritis.

Evangelisto A, Wakefield R, Emery P. · Academic Department of Musculoskeletal Medicine, First Floor, Old Nurses Home, Leeds General Infirmary, Great George Street, Leeds LSI 3EX, UK. · Best Pract Res Clin Rheumatol. · Pubmed #15501190 No free full text.

Abstract: Imaging can play a vital role in the evaluation of patients with early arthritis. Various imaging methods can be utilized to aid with diagnosis, predict prognosis and follow disease progression and treatment response. Previously, conventional radiography was the principal method used to evaluate and follow bone damage in patients with inflammatory arthritis. More recently the use of magnetic resonance imaging and ultrasonography has gained wider acceptance and popularity due to the ability of these multiplanar techniques to image both bone changes and soft tissue abnormalities, including synovitis. This chapter discusses the current imaging modalities used in the evaluation of patients with early arthritis, as well as the use of imaging in establishing the extent of disease, in prognosis and in monitoring disease course. Current data on imaging of patients with early arthritis due to rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis is reviewed.

Emery P, Suarez-Almazor M. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · Clin Evid. · Pubmed #15366179 No free full text.

This publication has no abstract.

Wakefield RJ, Conaghan PG, Jarrett S, Emery P. · Academic Department of Musculoskeletal Medicine, Leeds General Infirmary, UK. · Curr Opin Rheumatol. · Pubmed #15201608 No free full text.

Abstract: New imaging techniques such as ultrasound and MRI are likely to play increasing roles in the future management of patients with inflammatory arthritis, particularly those with rheumatoid arthritis and spondyloarthropathies. Ultrasound has a number of distinct advantages including its ability to scan multiple joints, safety, and immediately availability in clinic. MRI, however, is more sensitive and has a greater field of view because of its tomographic nature. Both modalities have the added advantage over radiography in that they can image soft tissue as well as bone. Dual X-ray absorptiometry already has an established role to play in the assessment of osteoporosis, but new techniques such as digital radiogrametry, quantitative CT, and ultrasound potentially will have a more important role to play in the future.

Kalden JR, Smolen JS, Emery P, van Riel PL, Dougados M, Strand CV, Breedveld FC. · Department of Internal Medicine III, Universitaet Erlangen-Nuremberg, Erlangen, Germany. · J Rheumatol Suppl. · Pubmed #15170905 No free full text.

Abstract: In most studies of disease modifying antirheumatic drug therapy, in combination with either leflunomide or biological agents, patients are given an additional agent after they have failed treatment with methotrexate (MTX). This review of clinical studies shows that leflunomide is clinically efficacious and well tolerated when added to either sulfasalazine or MTX, as both an initial and ongoing treatment for rheumatoid arthritis (RA). Experience in combining leflunomide with biological agents is limited to a small number of open-label studies with infliximab. According to the opinion obtained at an International Expert Panel Meeting held in Paris in May 2003, leflunomide can be used in combination therapy: 61% of the Expert Panel would use leflunomide with MTX, 71% with sulfasalazine, 43% with infliximab, 33% with adalimumab, 19% with etanercept, and 38% with anakinra. The Expert Panel stated that the combination of leflunomide and infliximab warrants a prospective, randomized, controlled trial in patients with incomplete clinical responses to leflunomide monotherapy, provided leflunomide is started first, without a loading dose, and infliximab is added after good tolerability to leflunomide has been established. The Expert Panel concluded that combination therapy with leflunomide has a place in the treatment of RA. Caution is advised, however, when using combination treatments and, therefore, the patient's safety should be carefully monitored.

van Riel PL, Smolen JS, Emery P, Kalden JR, Dougados M, Strand CV, Breedveld FC. · Department of Rheumatology, University Medical Centre Nijmegen, Nijmegen, The Netherlands. · J Rheumatol Suppl. · Pubmed #15170904 No free full text.

Abstract: The safety profile of leflunomide in the treatment of rheumatoid arthritis has been well documented in clinical trials, postmarketing surveillance, and epidemiological studies. Both postmarketing surveillance and epidemiological study results are consistent with the safety profile of leflunomide reported in clinical trials, and no increased risk was observed with leflunomide, compared with other disease modifying antirheumatic drugs; these studies have allowed a more precise representation of the incidence of adverse events occurring with leflunomide under normal conditions of care. The most common leflunomide-associated adverse events include diarrhea, elevated liver enzymes, alopecia, and rash. Ninety-five percent of the Expert Panel considered the adverse events associated with leflunomide to be manageable. If an adverse event required treatment to be stopped, many of the experts would consider subsequently restarting leflunomide. For minor adverse events, it was suggested that the physician might also consider using cholestyramine or charcoal to determine if the side effect is dose-related and, if it was, reduce the leflunomide dose accordingly. In addition to informing patients about the likelihood of side effects, it is important to emphasize that their incidence appears to diminish with continued treatment. It is also important to adequately support patients who are experiencing side effects and involve them in their disease management, for example, by offering the choice of reducing the leflunomide dose and/or having symptomatic treatment. Other patient management recommendations in this review reflect the views of the majority of participants as expressed in the meeting.

Smolen JS, Emery P, Kalden JR, Van Riel PL, Dougados M, Strand CV, Breedveld FC. · Division of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · J Rheumatol Suppl. · Pubmed #15170903 No free full text.

Abstract: This expert review of results from the leflunomide phase II and III clinical trials database demonstrates that leflunomide meets all 3 goals desired of disease modifying antirheumatic drug (DMARD) therapy: reducing the signs and symptoms of the disease; inhibiting structural damage; and improving physical function. Further, leflunomide has a rapid onset of action, sustained efficacy, and is effective in early and late disease, regardless of whether patients have received other DMARD previously. The consistent efficacy of leflunomide across phase III clinical trials is confirmed by the findings from clinical practice. Experts agreed that it is important to observe a patient under leflunomide monotherapy for at least 3-4 months before assessing efficacy. It is possible to start maintenance therapy, with either a daily dose of leflunomide 10 mg, subsequently changing to 20 mg, or the reverse. The decision to use a loading dose when initiating leflunomide therapy depends primarily on the balance between the tolerability and rapid efficacy associated with a loading dose, and the balance desired for an individual patient. In general, the use of both maintenance and loading doses requires a flexible approach to the treatment of rheumatoid arthritis. During the first few weeks of leflunomide therapy, patient dropout can be avoided by using prednisolone rather than a loading dose. Moreover, to ensure good tolerability and compliance in patients receiving a loading dose, information and adequate support should be provided throughout treatment.

Emery P. · Department of Rheumatology, Leeds General Infirmary, Leeds, England. · Pharmacoeconomics. · Pubmed #15157004 No free full text.

Abstract: As the cost of drug treatment for rheumatoid arthritis (RA) constitutes only a small proportion of total costs of the disease to individuals and society, therapeutic interventions have the potential for significant economic benefit. To take advantage of this potential, clinicians need to gain a global, long-term perspective on patient care. Economic evaluations of RA therapies are critically important in influencing decisions regarding the role of costly, but highly effective new therapies, particularly in settings where there are financial constraints on healthcare provisions. Such evaluations, therefore, need to be methodologically similar with valid results to enhance their value to clinicians and policy decision-makers. This requires the use of appropriate elements in the numerator (i.e. total number of dollars spent on healthcare as a result of the intervention) and the denominator (net health effectiveness) components of the cost-effectiveness equation. Other important design factors also need to be managed properly to ensure validity of the evaluation. In this regard, the guidelines proposed by the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Task Force represent a useful approach to help create common standards for economic evaluations in RA. Recently, the development of a number of decision analysis models in RA has helped predict the likely cost-effectiveness of new interventions such as the anti-tumour necrosis factor (TNF)-alpha agents, etanercept and infliximab, both of which have been found to be cost-effective relative to other disease-modifying anti-rheumatic drugs (DMARDs) using short-term efficacy endpoints. In comparisons of these two agents in patients with DMARD-resistant RA, etanercept has been shown to be more cost-effective than the combination of methotrexate and infliximab, administered in various dosages, over a period of 1 year using American College of Rheumatology (ACR) response rates as the primary efficacy measure. However, the criteria for determining clinical efficacy is paramount and other studies that use radiographic progression as a measure of clinical effectiveness show no difference between etanercept and infliximab in clinical efficacy. Important issues that need to be considered in developing economic models in RA include consideration of the connection between the prevention of radiographic progression and downstream economic consequences, and the need to employ lifetime models wherever possible because a long time period is necessary to determine the true cost-effectiveness of agents that modify radiographic progression of RA, such as etanercept, infliximab, and adalimumab. In doing so, it is hoped that such studies will provide optimal information to facilitate important decisions on resource allocation.

Emery P, Seto Y. · Academic Unit of Musculoskeletal Disease, Department of Rheumatology, 1st Floor, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, United Kingdom. · Clin Exp Rheumatol. · Pubmed #14969075 No free full text.

Abstract: Recent advances in the management and treatment of rheumatoid arthritis (RA) have provided evidence for the importance of early diagnosis and treatment of the disease. Biological therapy with monoclonal antibodies, including anti-tumor necrosis factor (TNF) agents have shown major efficacy in terms of disease activity and outcome of inflammatory arthritis in trials. Interest has focused on the treatment of early rheumatoid arthritis with anti-TNF agents to induce long-term impact on outcome. A major study of etanercept versus methotrexate (MTX) showed some benefit at one year for the etanercept group, but long-term data have shown greater benefit. Two double-blind placebo-controlled studies of infliximab in patients with early RA yielded promising data, showing the possibility of a true 'window of opportunity' with long-term benefit from a short term treatment period. Aggressive treatment by anti-TNF agents as well as combination therapies of disease modifying anti-rheumatic drugs (DMARDs) in patients with very early disease would be a logical approach to be investigated in the future.

Quinn MA, Emery P. · Academic Unit of Musculoskeletal Disease, Department of Rheumatology, Leeds General Infirmary, Leeds, United Kingdom. · Clin Exp Rheumatol. · Pubmed #14969068 No free full text.

Abstract: Therapeutic strategies for the treatment of rheumatoid arthritis (RA) have changed significantly in the last decade. The emphasis is now on early intervention with the aim of preventing disability and irreversible damage. Advocates of early intervention would suggest an alteration in the disease process, not just debulking of inflammatory disease. The data would at least support attenuation of the disease process with aggressive early therapy. Further research is required to elucidate the scientific mechanisms involved and their impact on the pathological progress of RA.

Wakefield RJ, Kong KO, Conaghan PG, Brown AK, O'Connor PJ, Emery P. · Academic Department of Musculoskeletal Medicine, General Infirmary at Leeds, Leeds, United Kingdom. · Clin Exp Rheumatol. · Pubmed #14969049 No free full text.

Abstract: Advances in ultrasound (US) and magnetic resonance imaging (MRI) techniques have provided new methods for evaluating early rheumatoid arthritis (RA). Their diagnostic properties in terms of detecting primary pathology of RA (i.e., erosions, bone changes, synovitis, tenosynovitis, and effusion) are reviewed. High-resolution US plays a significant role in therapeutic and diagnostic procedures. MRI also assists in the understanding of RA pathogenesis and joint mechanics.

Emery P. · Rheumatology and Rehabilitation Research Unit, University of Leeds, Leeds, United Kingdom. · Drugs Today (Barc). · Pubmed #14668929 No free full text.

Abstract: Adalimumab was approved by the U.S. Food and Drug Administration in 2002 for the treatment of moderate to severe rheumatoid arthritis and was granted approval from the European Medicines Evaluation Agency (EMEA) in September 2003. The standard dose is 40 mg given subcutaneously every other week, and the drug can be used alone or in combination with disease-modifying antirheumatic drugs such as methotrexate. The efficacy of adalimumab has been demonstrated in clinical trials with more than 2400 patients. In these trials, adalimumab has acted rapidly to reduce the signs and symptoms of disease, with responses sustained over the long term. The significant inhibition of disease progression seen with adalimumab has led to significant improvements in physical function and health-related quality of life. Data from the clinical safety database in nearly 2500 patients have also shown that the drug is generally safe and well-tolerated.

Emery P, Suarez-Almazor ME. · University of Leeds, Leeds, United Kingdom. · Am Fam Physician. · Pubmed #14620602 links to  free full text

This publication has no abstract.

Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Dougados M, Emery P, Gibofsky A, Kavanaugh AF, Keystone EC, Klareskog L, Russell AS, van de Putte LB, Weisman MH, Kavenaugh AF. · University of California, UCLA, Rheumatology, Division Los Angeles, USA. · Ann Rheum Dis. · Pubmed #14532138 links to  free full text

This publication has no abstract.