Rheumatoid Arthritis: Choy E

Choy E, Sattar N. · Sir Alfred Baring Garrod Clinical Trials Unit, Academic Department of Rheumatology, King's College, London, UK. · Ann Rheum Dis. · Pubmed #19286905 No free full text.

Abstract: In severe untreated rheumatoid arthritis (RA), reductions in high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and total cholesterol have been noted; this is in line with findings in other pathologies/conditions associated with inflammation or infection, such as sepsis, cancer, trauma or the postoperative period. Although the precise mechanisms remain to be established, cytokine-induced activation of the reticuloendothelial system is potentially critical to such changes. Consequently, dampening of inflammation in severe RA-as occurs with several biologics-may lead to increases, not only in high-density lipoprotein-cholesterol, but also with other lipid moieties, including total and low-density lipoprotein-cholesterol and, perhaps, triglycerides. This concept is consistent with findings following antitumour necrosis factor treatment and interleukin-6 receptor inhibition in patients with RA. At the same time, it is increasingly apparent that potent dampening of inflammation, however achieved, broadly reduces the risk of cardiovascular disease in RA. Therefore, changes in lipid profiles, particularly increases in cholesterol and triglycerides that occur with treatments for severe inflammation, may not represent increased cardiovascular risk as in the usual understanding of lipid-level elevations in individuals without significant inflammation. Rather, changes in lipid levels, in part or largely, may represent a predictable response to attenuation of inflammation. These observations are increasingly important clinically and should aid in the understanding and interpretation of lipid changes under inflammatory conditions, as well as in the context of potent anti-inflammatory interventions.

Pollard L, Choy E. · Sir Alfred Baring Garrod Clinical Trials Unit, Department of Academic Rheumatology, King's College, London Weston Education Centre, London, UK. · Curr Opin Rheumatol. · Pubmed #15838231 No free full text.

Abstract: PURPOSE OF REVIEW: The treatment of rheumatoid arthritis has been revolutionised in recent years with the advent of biologic treatments. The purpose of this review is to outline new treatments that target the inflammatory pathway in rheumatoid arthritis other than tumor necrosis factor-alpha. RECENT FINDINGS: As the use of anti-tumor necrosis factor-alpha treatment has become more widespread, the number of patients in whom this treatment is unsuccessful has also accumulated. Contraindications such as infection and cardiac failure further add to the number of patients who need alternative treatment. A better understanding of the inflammatory pathway in rheumatoid arthritis has led to interest in other therapeutic targets. Promising treatments such as interleukin-6 antagonists (MRA), CTLA4Ig (abatacept), and anti-B cell therapy (rituximab) have already been tested in randomized controlled trials over the past year. Other cytokines have been identified and have been shown to be of benefit in animal models, including interleukin-15, interleukin-17, and interleukin-18, and clinical trials of these agents are currently under way. SUMMARY: For patients with rheumatoid arthritis that does not respond to anti-tumor necrosis factor-alpha treatment, the promising alternatives MRA, abatacept, and rituximab have been tested. It is hoped that these agents will become available shortly.

Choy E. · Sir Alfred Baring Garrod Clinical Trials Unit, Academic Department of Rheumatology, 2nd Floor, Weston Education Centre, GKT School of Medicine, King's College Hospital, Cutcombe Road, London SE5 9PJ, UK. · Cytokine. · Pubmed #15588689 No free full text.

Abstract: Rheumatoid arthritis is a common debilitating disease. Chronic joint inflammation leads to irreversible joint damage. Disability is a common sequel, therefore it is a major healthcare burden. Treatment by convention disease modifying anti-rheumatic drugs improves symptoms and signs but does not improve long-term prognosis. Tumour necrosis factor alpha is a powerful pro-inflammatory cytokine. Blocking this cytokine by either monoclonal antibody or soluble receptor reduces inflammation, improves symptoms and significantly reduces joint damage. Tumour necrosis factor alpha antagonists are major breakthroughs in the treatment of rheumatoid arthritis. In the UK, they are approved for the treatment of rheumatoid arthritis in patients with active disease who have failed at least two disease modifying anti-rheumatic drugs.

Choy E. · Sir Alfred Baring Garrod Clinical Trials Unit, Department of Rheumatology, GKT School of Medicine, 2nd Floor, Weston Education Centre, King's College London, Cutcombe Road, London, UK SE5 9PJ. · Rheum Dis Clin North Am. · Pubmed #15172049 No free full text.

Abstract: Rheumatoid arthritis (RA) is a systemic disease that is associated with increased mortality and morbidity. Prognosis depends on disease severity and response to treatment. Those patients whose diseases are refractory to treatment with disease-modifying antirheumatic drugs (DMARDs) and have persistent inflammation have reduced survival similar to patients with triple-vessel coronary artery disease and Hodgkin's lymphoma. Although DMARDs reduce inflammation and improve symptoms, they do not improve long-term prognosis. Chronic synovial inflammation results in damage to the articular cartilage and adjacent bone. Consequently,after 10 years of disease most patients develop significant disability due to joint damage. Interleukin-6 (IL-6) is a key mediator of inflammation in RA. Inhibition of IL-6 reduces synovitis and improves symptoms. Therapies targeting IL-6 are promising new treatments for RA.

Choy E, Panayi G. · Department of Rheumatology, GKT School of Medicine, King's College, London. · Clin Exp Rheumatol. · Pubmed #10589353 No free full text.

Abstract: Second-line agents are used commonly for the treatment of rheumatoid arthritis (RA). They suppress inflammation and ameliorate symptoms but often fail to substantially improve long-term disease outcome. Their use in RA was discovered serendipitously and their modes of action were largely unknown. Recent researches have identified some of their mechanisms of action. Most of them have antiinflammatory properties and some are immunomodulators. Traditionally, second-line agents are used as monotherapy, but recent evidence suggests that combination treatment with two or more drugs may be more efficacious. However, the choice of agents in combination therapy is not based on their mechanisms of action. We review current knowledge on the modes of action of second-line agents and assess whether such understanding may offer a rational basis for combination therapy.

Emery P, Van Vollenhoven R, Ostergaard M, Choy E, Combe B, Graninger W, Krueger K, Matucci-Cerinic M, Navarro F, van Riel P, Settas L, Steinfeld S. · University of Leeds, Leeds, UK. · Ann Rheum Dis. · Pubmed #19286904 No free full text.

This publication has no abstract.

Fonseca JE, Santos MJ, Canhão H, Choy E. · Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. · Autoimmun Rev. · Pubmed #19189867 No free full text.

Abstract: Interleukin-6 (IL-6) is a cytokine that can facilitate autoimmune phenomena, amplify acute inflammation and promote the evolution into a chronic inflammatory state. In addition, it is a major promoter of bone resorption in pathological conditions. In particular, IL-6 has a pivotal role in synovitis, bone erosions and in the systemic features of inflammation. This cytokine specifically binds to IL-6 receptor (IL-6R), forming the IL-6/IL-6R complex that binds to gp130, a membrane-bound protein, which is involved in non-ligand-binding signal transduction. Targeting IL-6R in both animal models of arthritis and in rheumatoid arthritis patients with a humanized anti IL-6R monoclonal antibody (tocilizumab) effectively controls local and systemic inflammatory manifestations and blocks cartilage and bone destruction. Given the pleiotropic function of IL-6 it can be anticipated that other inflammatory diseases and bone metabolic conditions might benefit from selective IL-6 signaling inhibition.

Choy E. · Academic Department of Rheumatology, King's College London, London, UK. · Nat Clin Pract Rheumatol. · Pubmed #19107112 No free full text.

Abstract: Over the last decade, the use of tumor necrosis factor (TNF) inhibitors has improved the prognosis of patients with rheumatoid arthritis. Although these agents are more efficacious than traditional DMARDs, a substantial proportion of patients discontinue anti-TNF therapy because of adverse effects or lack of efficacy. Therapeutic options for these patients include dose increases, switching to an alternative TNF antagonist, or switching to a biologic of a different class, such as rituximab or abatacept. The recently published results of the RADIATE study by Emery et al. suggest that the interleukin-6 inhibitor tocilizumab is a safe and effective alternative for patients who fail to respond to anti-TNF therapy. Randomized controlled trials and the study of biomarkers are needed to help clinicians select the most suitable of these options for their patients.

Choy E. · Academic Department of Rheumatology, 2nd Floor, Weston Education Centre, King's College London, Cutcombe Road, London, SE5 9PJ, United Kingdom. · Curr Rheumatol Rep. · Pubmed #18817647 No free full text.

Abstract: Interleukin (IL)-6 is the most abundant proinflammatory cytokine in the circulation and synovial joints of patients with active rheumatoid arthritis. It has pivotal roles in the immune response and inflammation. In rheumatoid arthritis, it causes synovitis, joint destruction, and many systemic manifestations. Clinical trials of tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody that blocks IL-6 signaling, have demonstrated therapeutic benefit. It heralds a new era of anticytokine therapy in rheumatoid arthritis.

Sokka T, Hetland ML, Mäkinen H, Kautiainen H, Hørslev-Petersen K, Luukkainen RK, Combe B, Badsha H, Drosos AA, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Burmester GR, Tunc R, Dimić A, Nedović J, Stanković A, Bergman M, Toloza S, Pincus T, Anonymous00028. · Jyväskylä Central Hospital, Jyväskylä, Finland, and Medcare Oy, Aänekoski, Finland. · Arthritis Rheum. · Pubmed #18759292 No free full text.

Abstract: OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >/=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Naranjo A, Sokka T, Descalzo MA, Calvo-Alén J, Hørslev-Petersen K, Luukkainen RK, Combe B, Burmester GR, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Tunc R, Dimic A, Bergman M, Toloza S, Pincus T, Anonymous00244. · Hospital de Gran Canaria Dr, Negrin, University of Las Palmas de Gran Canaria, Barranco de la Ballena s/n 35011, Spain. · Arthritis Res Ther. · Pubmed #18325087 links to  free full text

Abstract: INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. RESULTS: Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries. CONCLUSION: In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.

Choy E. · Academic Department of Rheumatology, GKT School of Medicine, King's College Hospital, London, UK. · Ann Rheum Dis. · Pubmed #14532153 links to  free full text

This publication has no abstract.

Kirwan JR, Minnock P, Adebajo A, Bresnihan B, Choy E, de Wit M, Hazes M, Richards P, Saag K, Suarez-Almazor M, Wells G, Hewlett S. · University of Bristol Academic Rheumatology Unit, and United Bristol Healthcare NHS Trust, Bristol, UK. · J Rheumatol. · Pubmed #17477482 No free full text.

Abstract: The Patient Perspective Workshop at OMERACT 8 considered evidence for the importance of fatigue to patients with rheumatoid arthritis (RA) and whether measurement of fatigue meets the requirements of the OMERACT filter. The workshop participants included 20 patients from 10 countries and 60 other OMERACT participants. Introductory papers and detailed notes for discussion group members set out the evidence from the literature and from recent analyses of clinical study data available to several participants. The workshop concluded that fatigue is a symptom that is important to patients, is commonly reported by patients, is often severe, can be measured by several current instruments that pass the OMERACT filter, is responsive to some interventions, and provides information additional to that commonly obtained from currently used outcomes. The final OMERACT plenary session endorsed by a very large majority (89%) the proposal that, in addition to the "core set" of outcome measures currently in widespread use, fatigue should be measured in future studies of RA whenever possible.