Rheumatoid Arthritis: Moots R

Goodacre J, Moots R. · No affiliation provided · Cytokine. · Pubmed #15588687 No free full text.

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Moots R, Taggart A, Walker D. · No affiliation provided · Rheumatology (Oxford). · Pubmed #12709535 links to  free full text

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Chitale S, Moots R. · University of Liverpool, Academic Rheumatology Unit, School of Clinical Sciences, University Hospital Aintree, Longmoor Lane, Liverpool L9 7AL, UK. · Expert Opin Biol Ther. · Pubmed #18081541 No free full text.

Abstract: Rheumatoid arthritis (RA) is a multisystem autoimmune disease, of unknown aetiology with high morbidity and significantly increased mortality. Over recent years, the introduction of targeted therapies with biologic agents have made major inroads to the outcomes in RA.The first such agents developed were TNF-alpha inhibitors. However, despite their high efficacy, up to 30% patients fail to respond adequately, or develop adverse reaction to TNF-alpha inhibitors. This suggests that other pathological mechanisms are involved, in addition to those mediated by TNF-alpha. Abnormal T-cell function has long been thought to play a key role in the pathogenesis of RA, stimulating both the production of pro-inflammatory cytokines and recruitment of other inflammatory cells, resulting in joint destruction and systemic disease. Abatacept, the first of a group of T-cell co-stimulation modulators, targeting T-cell activation, has recently been licensed for use in RA and shows promise as a useful drug to treat this major disabling disease.

Hodgson RJ, O'Connor P, Moots R. · MARIARC, Pembroke Place, Liverpool L69 3GE, UK. · Rheumatology (Oxford). · Pubmed #18045811 No free full text.

Abstract: Magnetic resonance imaging (MRI) allows the direct visualization of many bone and soft tissue changes in rheumatoid arthritis. Synovitis volume, bone marrow oedema and bone erosions are suitable for serial measurement. The outcome measures in rheumatoid arthritis clinical trials (OMERACT) rheumatoid arthritis magnetic resonance imaging (RAMRIS) system is designed to allow straightforward, reproducible scoring of all these features. Alternatively, synovial volumes may be directly and quickly measured using semi-automated techniques. There is the potential for similar systems for measuring erosions. Dynamic contrast enhanced MRI depends on the rate of enhancement of the synovium after intravenous contrast agent. Measurements depend on the underlying physiology of the inflamed synovium, in particular the vascularity and capillary permeability which are expected to closely mirror inflammatory activity in the joint. Measurements from MRI have been shown to correlate with clinical, laboratory, imaging and histological measures of inflammation, predict erosive progression and respond rapidly to various types of treatment. They are, therefore, expected to be good measures of disease activity, progression and response to therapy.

Barnes T, Moots R. · Academic Rheumatology, University of Liverpool, UK. · Int J Nanomedicine. · Pubmed #17722505 links to  free full text

Abstract: Anti-TNFalpha therapy has revolutionized the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. These drugs are powerful and expensive. A new anti-TNFalpha agent, a nanomolecule comprising a humanized Fab' antibody fragment against TNFalpha with a polyethylene glycol tail, is shortly to complete phase III trials in RA. In this review we will discuss the construct of this new molecule, data from trials so far, and its potential place in the market place.

Maddison P, Kiely P, Kirkham B, Lawson T, Moots R, Proudfoot D, Reece R, Scott D, Sword R, Taggart A, Thwaites C, Williams E. · Department of Rheumatology, Ysbyty Gwynedd Hospital, University of Wales, Bangor LL57 2PW, UK. · Rheumatology (Oxford). · Pubmed #15657072 links to  free full text

Abstract: OBJECTIVES: To determine, by consensus, the optimal use of leflunomide in rheumatoid arthritis (RA), using a multidisciplinary panel of experts and performing meta-analyses of available data. METHODS: A multidisciplinary panel of experts in RA was convened. Important questions, pertinent to the use of leflunomide in the treatment of RA, were defined by consensus at an initial meeting. Each question was allocated to subgroups of two or three members, who worked separately to prepare a balanced opinion, based on published literature, data from individual patients taking part in phase II and phase III clinical trials provided by Aventis, and data from a USA-based medical claims database (AETNA). The full group then reconvened to agree on an overall consensus statement. Recommendations concerning efficacy and tolerability versus comparator drugs and placebo were derived from two new meta-analyses. RESULTS: Leflunomide was at least as effective as sulphasalazine and methotrexate, and equally well tolerated on meta-analysis of trial data. Overall withdrawal rates for all adverse events were similar for all three drugs. Avoidance of the loading dose reduces 'nuisance' side-effects (e.g. nausea), but probably delays the onset of action. Adverse events could usually be managed by dose reduction and/or symptomatic therapy. CONCLUSIONS: On the basis of efficacy, safety and cost, leflunomide should be considered in patients with RA who have failed first-line DMARD drug therapy. In refractory cases, leflunomide may be used in combination with, for example, methotrexate before biological agents. Therapy should be initiated by a specialist, but repeat prescribing in general practice on a shared care basis is acceptable using agreed protocols. Clear mechanisms are required to monitor toxicity, with good communication between the patient and rheumatologist to manage nuisance side-effects and avoid unnecessary discontinuation of leflunomide.

Hodgson RJ, Barnes T, Connolly S, Eyes B, Campbell RS, Moots R. · MARIARC, University of Liverpool, Pembroke Place, Liverpool, L69 3GE, UK. · Skeletal Radiol. · Pubmed #18058095 No free full text.

Abstract: OBJECTIVE: Dynamic contrast-enhanced MRI of patients with rheumatoid arthritis has shown a decrease in the early enhancement rate (EER) of synovitis after treatment. The purpose of this work was to investigate the underlying changes. METHODS: 3D dynamic contrast-enhanced images were acquired from 13 patients before and 1-2 weeks after anti-TNF alpha treatment. The EER of the inflamed synovium was measured. The T1 relaxation time of the synovitis was calculated from images at different flip angles. The time course of the arrival of gadolinium at the radial artery was determined. The gadolinium enhancement of the inflamed synovium was modeled to calculate the fractional plasma volume (vp), the fractional extravascular, extracellular fluid volume (ve), and the volume transfer constant (Ktrans). Pre- and post-treatment values were compared and the dependence of the EER on each parameter was assessed. RESULTS: There was a decrease in the EER measured over 26 s after treatment (29%, p = 0.002). Reductions in T1 (12%, p = 0.001), Ktrans (31%, p = 0.002), and vp (43%, p = 0.01) contributed to this; however, the EER was relatively insensitive to changes in ve. CONCLUSIONS: The decrease in EER after anti-TNF alpha treatment is largely caused by reductions in the volume transfer constant Ktrans, the fractional plasma volume vp, and the T1 relaxation time. Only the contributions from Ktrans and vp directly reflect synovial vascularity.

Hodgson R, Grainger A, O'Connor P, Barnes T, Connolly S, Moots R. · MARIARC, Pembroke Place, Liverpool L69 3GE, UK. · Ann Rheum Dis. · Pubmed #17965120 No free full text.

Abstract: AIMS: The aim of this work was to assess the feasibility of using dynamic contrast enhanced (DCE) MRI of bone marrow oedema, to compare it with conventional marrow oedema scoring systems, and to determine the effects of anti-tumour necrosis factor (TNF)alpha therapy. METHODS: The wrist and metacarpophalangeal (MCP) joints of 25 patients with rheumatoid arthritis were studied. A total of 14 were imaged before and 1-2 weeks after anti-TNFalpha therapy. T2-weighted fat-suppressed images were collected. A dynamic series of 24 3D spoiled gradient-echo images were acquired before, during and after the intravenous administration of gadolinium-based contrast medium. Oedema was scored using the conventional Rheumatoid Arthritis MRI Scoring (RAMRIS) system from T2-weighted images. The relative enhancement rate (RER) was calculated using the dynamic series from oedematous bone, bone adjacent to oedema and from an uninvolved bone. RESULTS: A total of 56% of patients showed bone marrow oedema. The RER was significantly increased in and adjacent to areas of marrow oedema. There was a significant reduction in the RER after treatment, but not in the RAMRIS score. CONCLUSIONS: Dynamic contrast enhanced MRI of bone marrow oedema yields additional information to RAMRIS scoring and may be a more sensitive marker of inflammatory activity and response to treatment.

Hodgson RJ, Connolly S, Barnes T, Eyes B, Campbell RS, Moots R. · Magnetic Resonance and Image Analysis Research Centre, and School of Clinical Sciences, University of Liverpool, Liverpool, and Whiston Hospital, Merseyside, UK. · Magn Reson Med. · Pubmed #17763341 No free full text.

Abstract: Dynamic contrast-enhanced MRI (DCE-MRI) of the hand and wrist was performed in 11 patients with rheumatoid arthritis twice before and once 2 weeks after treatment with anti-tumor necrosis factor (TNF)-alpha therapy. A rapid, T1-weighted 3D spoiled gradient echo (SPGR) sequence was used for the dynamic imaging. T1 estimation was performed using similar images obtained at different flip angles. The relative radiofrequency field was estimated from the known T1 of the periarticular fatty marrow. The arterial input function (AIF) was measured at each examination, and normalized to the expected plasma concentration to reduce partial volume effects. Synovial enhancement was modeled to yield values for Ktrans, ve, and vp. Ktrans and ve showed good reproducibility. There was a significant decrease of about 20% in Ktrans after 2 weeks of treatment. This study demonstrates the potential of DCE-MRI and pharmacokinetic modeling to study early changes in inflammatory activity in rheumatoid arthritis following treatment.

Hutchinson D, Shepstone L, Moots R, Lear JT, Lynch MP. · Rheumatology Research Group, University Hospital Aintree, Liverpool, UK. · Ann Rheum Dis. · Pubmed #11171682 links to  free full text

Abstract: OBJECTIVES: To investigate the potential relation between cumulative exposure to cigarette smoking in patients with or without rheumatoid arthritis (RA) and a positive family history of the disease. METHODS: 239 outpatient based patients with RA were compared with 239 controls matched for age, sex, and social class. A detailed smoking history was recorded and expressed as pack years smoked. Conditional logistic regression was used to calculate the association between RA and pack years smoked. The patients with RA were also interviewed about a family history of disease and recorded as positive if a first or second degree relative had RA. The smoking history at the time of the study of the patients with RA with or without a family history of the disease was compared directly with that of their respective controls. Patients with RA with or without a family history of the disease were also compared retrospectively for current smoking at the time of disease onset. RESULTS: An increasing association between increased pack years smoked and RA was found. There was a striking association between heavy cigarette smoking and RA. A history for 41-50 pack years smoked was associated with RA (odds ratio (OR) 13.54, 95% confidence interval (95% CI) 2.89 to 63.38; p<0.001). The association between ever having smoked and RA was modest (OR 1.81, CI 1.22 to 2.19; p=0.002). Furthermore, cigarette smoking in the patients with RA without a positive family history of RA was more prevalent than in the patients with a positive family history of RA for ever having smoked (72% v 54%; p=0.006), the number of pack years smoked (median 25.0 v 4.0; p<0.001), and for smoking at the time of disease onset (58% v 39%; p=0.003). CONCLUSIONS: Heavy cigarette smoking, but not smoking itself, is strongly associated with RA requiring hospital follow up and is markedly more prevalent in patients with RA without a family history of RA.

Hutchinson D, Moots R. · No affiliation provided · Rheumatology (Oxford). · Pubmed #11752525 links to  free full text

This publication has no abstract.

Hutchinson D, Moots R. · No affiliation provided · Ann Rheum Dis. · Pubmed #11345081 links to  free full text

This publication has no abstract.