Rheumatoid Arthritis: Ostör AJ

Kuek A, Hazleman BL, Ostör AJ. · Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, UK. · Postgrad Med J. · Pubmed #17403952 No free full text.

Abstract: Targeted biologic therapies have revolutionised treatment of immune-mediated inflammatory diseases (IMIDs) due to their efficacy, speed of onset and tolerability. The discovery that clinically unrelated conditions, such as rheumatoid arthritis and Crohn's disease, share similar immune dysregulation has led to a shift in the management of IMIDs from one of organ-based symptom relief to mechanism-based treatment. The fact that anticytokine therapy has been effective in treating multiple orphan inflammatory conditions confirms the IMID paradigm. In this review we examine the biologic agents currently licensed for use in the US and Europe: infliximab, etanercept, adalimumab, rituximab, abatacept, anakinra, alefacept and efalizumab. We also discuss the rationale behind the management of IMIDs using rheumatoid arthritis, Crohn's disease, psoriasis and psoriatic arthritis as examples. For the medical profession, IMID represents a breakthrough in the way pathology is classified. In this burgeoning era of biologic therapy the prospect of complete disease remission is conceivable.

Ostör AJ. · Department of Rheumatology, Addenbrooke's Hospital, Cambridge. · Clin Med. · Pubmed #16011212 No free full text.

Abstract: Biologics have revolutionised the treatment of RA due to their efficacy, speed of onset and tolerability. Increasing evidence suggests that early intervention is the key to combating RA. The future challenge is to find the best time to introduce biologics into the treatment paradigm in the hope of inducing disease remission--something unthinkable even a decade ago.

Ostör AJ. · Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. · Clin Rheumatol. · Pubmed #18670735 No free full text.

Abstract: Rheumatoid arthritis (RA) is a debilitating autoimmune disease that has traditionally been treated with disease-modifying anti-rheumatic drugs (DMARDs). In the European Union (EU), patients who fail to respond to traditional DMARDs may receive tumor necrosis factor-alpha (TNF-alpha) antagonists. However, approximately one-third of patients fail TNF-alpha antagonists due to adverse effects or lack of efficacy, and there are limited treatment options available to these patients. As knowledge of the underlying immunopathology of RA evolves, new strategies for inhibiting the inflammatory process have emerged. It is well known that activated T cells play a key role in orchestrating the immunopathological mechanisms of RA. Inhibiting the full activation of T cells is a rational strategy in the treatment of RA and represents a novel method of inhibiting disease activity, distinct from inflammatory cytokine blockade. Here, the safety and efficacy of abatacept, a selective T-cell co-stimulation modulator recently approved in the EU, is reviewed in patients with RA who have shown an inadequate response to TNF-alpha antagonists. In a randomized, placebo-controlled, double-blind, phase III trial of patients with an inadequate response to TNF-alpha antagonism, abatacept was effective in improving the signs and symptoms of RA, as well as patient-centered outcomes, such as fatigue, disability, and other mental and physical aspects of health-related quality of life. These improvements were sustained through 2 years during the open-label, long-term extension period. In this trial, abatacept demonstrated a safety and tolerability profile similar to placebo. Taken together, these data suggest that selective co-stimulation modulation with abatacept may be a viable option for patients who are refractory to both traditional therapies and TNF-alpha antagonists.

Ostör AJ, Conaghan PG. · School of Clinical Medicine, University of Cambridge, Clinical Research Unit. · Practitioner. · Pubmed #19418700 No free full text.

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Kiely PD, Brown AK, Edwards CJ, O'Reilly DT, Ostör AJ, Quinn M, Taggart A, Taylor PC, Wakefield RJ, Conaghan PG. · Department of Rheumatology, St Georges Healthcare NHS Trust, London, UK. · Rheumatology (Oxford). · Pubmed #19401359 No free full text.

Abstract: OBJECTIVE: RA has a substantial impact on both patients and healthcare systems. Our objective is to advance the understanding of modern management principles in light of recent evidence concerning the condition's diagnosis and treatment. METHODS: A group of practicing UK rheumatologists formulated contemporary management principles and clinical practice recommendations concerning both diagnosis and treatment. Areas of clinical uncertainty were documented, leading to research recommendations. RESULTS: A fundamental concept governing treatment of RA is minimization of cumulative inflammation, referred to as the inflammation-time area under the curve (AUC). To achieve this, four core principles of management were identified: (i) detect and refer patients early, even if the diagnosis is uncertain: patients should be referred at the first suspicion of persistent inflammatory polyarthritis and rheumatology departments should provide rapid access to a diagnostic and prognostic service; (ii) treat RA immediately: optimizing outcomes with conventional DMARDs and biologics requires that effective treatment be started early-ideally within 3 months of symptom onset; (iii) tight control of inflammation in RA improves outcome: frequent assessments and an objective protocol should be used to make treatment changes that maintain low-disease activity/remission at an agreed target; (iv) consider the risk-benefit ratio and tailor treatment to each patient: differing patient, disease and drug characteristics require long-term monitoring of risks and benefits with adaptations of treatments to suit individual circumstances. CONCLUSION: These principles focus on effective control of the inflammatory process in RA, but optimal uptake may require changes in service provision to accommodate appropriate care pathways.

Pocock JM, Vasconcelos JC, Ostör AJ. · Department of Rheumatology, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. · Rheumatology (Oxford). · Pubmed #18503089 No free full text.

Abstract: OBJECTIVES: The optimal therapeutic trial duration of anti-TNF-alpha therapy is currently unknown. The British Society for Rheumatology (BSR) guidance states that non-response at 3 months warrants re-evaluation of treatment and recommends not to persist beyond 6 months. The National Institute for Health and Clinical Excellence (NICE) specifies treatment continuation if response is achieved by 6 months, yet the European League against Rheumatism (EULAR) and the American College of Rheumatology (ACR) maintain a 3 month cut-off. No evidence exists to support a 6 month therapeutic trial over 3 months. Thus, we undertook a study to evaluate the proportion of patients who failed to meet NICE response criteria at 3 months but obtained this by 6 months, and to identify predictive factors for this. METHODS: Patients who commenced anti-TNF-alpha therapy for RA were studied, counting those who switched to a second or third agent separately for each instigation of therapy (n = 244). Response at 3 and 6 months was defined according to NICE criteria as a >or=1.2 reduction in Disease Activity Score (DAS28). RESULTS: Of the 189 patients with available 3 month DAS28 responses, 149 fulfilled response criteria. Of the 40 who failed, 27 continued treatment, of whom 21 were available for follow-up at 6 months. Out of the 21 patients, 12 (57%; 95% CI 36, 78) achieved a response at this time. This data set was too small to investigate predictors of response at 6 months. CONCLUSIONS: A substantial proportion of patients who fail NICE response criteria at 3 months and continue on treatment to 6 months achieve a response. These results support a 6 month therapeutic trial over 3 months.

Kuek A, Hazleman BL, Gaston JH, Ostör AJ. · No affiliation provided · Rheumatology (Oxford). · Pubmed #16920752 links to  free full text

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Ostör AJ, Chilvers ER, Somerville MF, Lim AY, Lane SE, Crisp AJ, Scott DG. · Rheumatology Department, Addenbrooke's Hospital, Cambridge, UK. · J Rheumatol. · Pubmed #16511933 No free full text.

Abstract: We describe 5 patients with rheumatoid arthritis (RA) who developed pulmonary complications following infliximab therapy; 4 patients had preexisting usual interstitial pneumonia. As the pathophysiology of the pulmonary insult is unknown, we advise caution in the use of anti-tumor necrosis factor-alpha therapy in patients with RA with underlying lung disease of sufficient severity to withhold methotrexate treatment.

Burr ML, Malaviya AP, Gaston JH, Carmichael AJ, Ostör AJ. · No affiliation provided · Rheumatology (Oxford). · Pubmed #18375402 No free full text.

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Kuek A, Weerakoon A, Ahmed K, Ostör AJ. · No affiliation provided · Rheumatology (Oxford). · Pubmed #17449487 links to  free full text

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Kuek A, Ostör AJ. · No affiliation provided · Joint Bone Spine. · Pubmed #17350310 No free full text.

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Clement SA, Burrows NP, Sansome A, Hazleman BL, Ostör AJ. · No affiliation provided · Clin Rheumatol. · Pubmed #17119860 No free full text.

This publication has no abstract.