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P Emery

Publications and source records attributed to P Emery.

At least 19 recordsLinked to original sources
PubMed2007

Microdamage and altered vascularity at the enthesis-bone interface provides an anatomic explanation for bone involvement in the HLA-B27-associated spondylarthritides and allied disorders.

OBJECTIVE: To describe the basis for entheseal-associated bone disease in the spondylarthritides, by analyzing microanatomic and histopathologic relationships between soft tissue, bone cortex, and adjacent trabeculae. METHODS: Serial sections from 52 entheses were examined; these entheses encompassed small and large insertions in the upper limb (n = 21), lower limb (n = 27), and spine (n = 4) from 60 cadavers. Enthesis microdamage (fissuring) as well as vascular and reparative changes were evaluated. Contact radiographs were used to ascertain the relationship between entheses and the trabecular network. RESULTS: At virtually all fibrocartilaginous entheses, the deep cortical boundary was extremely thin (typically 50-600 microm) or indistinguishable, and 96% of entheses had small holes in the cortical shell (typically 100-400 microm wide). Such regions were frequent sites of bone formation and renewal (96%) and microdamage (31%); these changes were more common in the lower limb. The presence of blood vessels near holes in the cortical shell was common; in 85% of attachments, blood vessels were present on the soft tissue side of the enthesis. Highly orientated trabeculae were more obvious in the lower limb than the upper limb (59% versus 29%). CONCLUSION: The trabecular network supporting the cortical shell is an integral part of the enthesis, transferring load to an extensive skeletal region. In many cases, tendons/ligaments are anchored directly to such networks. This functional integration is associated with microdamage and repair at the hard tissue-soft tissue interface. These findings have implications for understanding bone involvement in SpA and for the SpA concept in general, especially the hypothesis that enthesis-bone architecture may be important in disease initiation.

Aged↗
PubMed2006

Consensus statement on the use of rituximab in patients with rheumatoid arthritis.

A large number of experts experienced in the treatment of rheumatoid arthritis were involved in formulating a consensus statement on the use of B cell-targeted treatment with rituximab in patients with rheumatoid arthritis. The statement was supported by data from randomised controlled clinical trials and the substantial literature on oncology. The statement underwent three rounds of discussions until its ultimate formulation. It should guide clinicians in the use of this newly approved biological agent in treating patients with rheumatoid arthritis.

Antibodies, Monoclonal↗
PubMed2006

Sustained benefit in rheumatoid arthritis following one course of rituximab: improvements in physical function over 2 years.

OBJECTIVES: To evaluate the long-term impact on physical function of a single course of rituximab in rheumatoid factor, seropositive patients with active rheumatoid arthritis (RA) despite ongoing methotrexate treatment. METHODS: A randomized, controlled trial comparing rituximab alone [1,000 mg intravenously (iv) on days 1 and 15, n= 40], or in combination with cyclophosphamide (750 mg iv on days 3 and 7, n= 41) or oral methotrexate (> or =10 mg/week, n= 40) with placebo + methotrexate (> or =10 mg/week, n= 40), resulted in significant reductions in disease activity at weeks 24 and 48. Sustained improvements in physical function and standard effect sizes (SES) for changes in components of ACR and EULAR criteria were evaluated over 2 yrs. RESULTS: More patients receiving rituximab + methotrexate completed a 2-yr follow-up without further treatment than those receiving placebo + methotrexate (45% vs 15%, respectively), rituximab alone (10%) or rituximab + cyclophosphamide (22%). This reflected a higher percentage of patients receiving rituximab + methotrexate reporting improvements in Health Assessment Questionnaire Disability Index > or = minimum clinically important difference at 1 and 2 yrs (68% and 30%, respectively) compared with placebo + methotrexate (28% and 15%), rituximab monotherapy (43% and 10%) or rituximab + cyclophosphamide (39% and 12%). SES were high in all rituximab groups and revealed differing patterns of response over time. CONCLUSION: A single course of rituximab with continuing methotrexate in patients with active RA provided clinically meaningful improvements in physical function over 2 yrs, with lower discontinuation rates and larger SES for improvements in ACR and EULAR criteria components.

Adult↗
PubMed2006

Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment.

OBJECTIVE: To examine the impact of added abatacept treatment on health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX). METHODS: The impact of abatacept treatment on HRQoL was examined in a longitudinal, randomised double blind, placebo controlled clinical trial. Effects of treatment on HRQoL were examined using repeated measures analysis of covariance and comparing rates of change in HRQoL across treatment groups. The relationship between American College of Rheumatology (ACR) clinical markers and disease duration with changes in HRQoL indicators was also examined. Finally, a responder analysis was used to examine the percentage of patients who improved by 0.5 SD in 12 months or who reached the normative levels seen in the US general population. RESULTS: Statistically significant improvements in the abatacept group relative to controls were observed across a range of HRQoL measures, including physical function, fatigue, all eight domains of the SF-36, and the physical and mental component summaries (PCS and MCS). Improvements were seen as early as day 29 for fatigue and for five out of eight SF-36 domains. By day 169, all HRQoL measures were significantly better with abatacept than with placebo. HRQoL gains were associated with greater ACR clinical improvement, and the effects were consistent for patients with different disease duration. A significantly greater percentage of patients treated with abatacept reached normative levels of PCS, MCS, physical functioning, and fatigue compared with patients treated with MTX alone. CONCLUSION: Combined abatacept and MTX treatment produces significant improvements across a wide range of HRQoL domains in patients with RA.

Abatacept↗
PubMed2006

Submaximal exercise testing in the assessment of interstitial lung disease secondary to systemic sclerosis: reproducibility and correlations of the 6-min walk test.

BACKGROUND: The 6-min walk test (6MWT) is increasingly used as an outcome measure in interstitial lung disease (ILD). AIM: To evaluate the usefulness of the 6MWT in a cohort of patients with ILD secondary to systemic sclerosis (SSc) and to correlate with established physiological parameters. METHODS: 163 patients with SSc-ILD were recruited for a multicentre, randomised, double-blind clinical trial. Available data at protocol screening included repeated 6MWTs, pulmonary function testing with diffusing capacity, Doppler echocardiography and high-resolution computed tomography of the thorax. Borg Dyspnoea Index was evaluated before and after 6MWT. RESULTS: Mean (standard deviation (SD)) distance walked during walk test 1 was 396.6 (84.55) m compared with 399.5 (86.28) m at walk test 2. The within-subject, intertest correlation as determined by Pearson's correlation coefficient testing was 0.95 (p<0.001). However, only weak correlations of 6MWT with percentage forced vital capacity and the Borg Dyspnoea Index were observed, and no correlation was observed with percentage diffusing capacity. CONCLUSION: These data confirm the high reproducibility of the 6MWT in patients with SSc-ILD and therefore the validity of the test in this cohort. The lack of correlation of 6MWT with standard physiological parameters of ILD suggests a multifactorial basis for limited exercise capacity in patients with SSc and calls into question the utility of the 6MWT as a measure of outcome in future studies on SSc-ILD.

Adult↗
PubMed2006

The relationship between the extensor tendon enthesis and the nail in distal interphalangeal joint disease in psoriatic arthritis--a high-resolution MRI and histological study.

OBJECTIVES: Diffuse swelling of the distal interphalangeal (DIP) joint beyond the joint margin is a common feature of arthritis in psoriatic arthritis (PsA). The purpose of this study was to explore the microanatomical basis for the inflammation and nail disease in PsA using a combined high-resolution magnetic resonance imaging (MRI) and histological studies. METHODS: High-resolution MRIs of the DIP joint were obtained in 30 subjects [10 PsA, 10 osteoarthritis (OA) and 10 normal volunteers]. The relationship between the DIP joint capsule and associated tendon enthesis and the nail bed and root were evaluated. Histological studies to define the relationship between the normal cadaveric DIP joint capsule and the nail root were performed on the middle and ring fingers of 10 dissecting room cadavers. RESULTS: On MRI, the dorsal capsular enthesis was the epicentre of an inflammatory reaction. This extended to involve the soft tissues adjacent to the nail in 8 of 10 cases in PsA, but only 4 of 10 cases in OA where the inflammation is less intense and in none of the normal fingers. The DIP joint capsule was intimately linked with the nail complex on histology, with the dorsal, volar and lateral aspects of the nail bed being ensheathed in fibres extending from the entheses. CONCLUSION: The study suggests that the extended nature of the enthesis organ associated with the DIP joint may explain the diffuse nature of the inflammatory response around the nail in PsA. Therefore the nail is as much an integral part of the enthesis organ as it is of the skin, which has implications for a better understanding of the disease.

Adolescent↗
PubMed2006

Estimating the cost and health status consequences of treatment with TNF antagonists in patients with psoriatic arthritis.

OBJECTIVES: Tumour necrosis factor (TNF) has been shown to improve the outcomes in patients with psoriatic arthritis (PsA). We estimate the long-term impact on health status of prescribing the TNF antagonist etanercept, and evaluate the cost-effectiveness in a health economic model. METHODS: The relationship between disability (Health Assessment Questionnaire) and health state utility was explored to estimate the quality-adjusted life years (QALYs) gained from the TNF antagonist etanercept. A model was then used to compare sequences of treatments for PsA after failure of two conventional disease modifying anti-rheumatic drugs (DMARDs). One arm commences on etanercept therapy and this is compared with a strategy commencing with combination therapy of methotrexate and ciclosporin and another commencing with leflunomide. Individual patient data from Phase III etanercept trials is used to populate the model supported by published evidence from extensive literature searches. By incorporating a life table specific for a PsA population, and using a number of evidence- and expert opinion-based assumptions for disease progression, the model was extended beyond the trial duration to a 10-yr time horizon. Cost offsets were produced by avoiding surgery through delayed progression; drug and monitoring costs were also modelled. RESULTS: Over the 10 yrs, modelled etanercept treatment gave 0.82 more QALYs when compared with combination therapy with methotrexate and ciclosporin, and 0.65 more QALYs in comparison with leflunomide. This equates to a central estimate for the cost per QALY of pound28 189 and pound28 189 for ciclosporin and leflunomide, respectively. Sensitivity analyses demonstrated this could vary by as much as +/-28%. CONCLUSIONS: With limited data currently available, the potential cost-effectiveness of etanercept in DMARD failures for adults with PsA appears encouraging. The result for other TNF antagonists will depend on how their relative efficacy and drug price compares with etanercept. A number of limitations are described and priorities for further research suggested.

Adult↗
PubMed2006

Combined high-resolution magnetic resonance imaging and histological examination to explore the role of ligaments and tendons in the phenotypic expression of early hand osteoarthritis.

BACKGROUND: The pathogenesis of the early stages of hand osteoarthritis is poorly understood, but recent high-resolution magnetic resonance imaging (hrMRI) studies suggest that the joint ligaments have a major role in the phenotypic expression of the disease. OBJECTIVE: To combine hrMRI and cadaveric histological studies to better understand the mechanisms of damage, and especially the role of joint ligaments and tendons in disease expression. METHODS: hrMRI was carried out in the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints in 20 patients with osteoarthritis, with a disease duration < or = 12 months. Histological sections of the DIP and PIP joints were obtained from three dissecting-room specimens for comparative analysis. RESULTS: The collateral ligaments influenced the location of both hrMRI-determined bone oedema and bone erosion in early osteoarthritis. These changes were best understood in relation to the enthesis organ concept, whereby the interaction between ligament fibrocartilages leads to bone disease. Normal ligaments were commonly associated with microdamage at insertions corresponding to ligament thickening noted in early osteoarthritis. The ligaments also influenced the location of node formation in early osteoarthritis. The DIP extensor tendon insertions were associated with the development of a neoarticular surface. CONCLUSIONS: Small-joint collateral ligaments and tendons have a central role in the early stages of hand osteoarthritis, and determine the early expression of both the soft tissue and bony changes in disease.

Aged↗
PubMed2006

Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood.

OBJECTIVE: Our aim was to test the hypothesis that there is a deficit in the CD4+CD25high regulatory T-cell population in early rheumatoid arthritis (RA), either in size or functional activity. METHODS: Peripheral blood mononuclear cells were examined from subjects with early active RA who had received no previous disease-modifying therapy (n = 43), from individuals with self-limiting reactive arthritis (n = 14), from subjects with stable, well-controlled RA (n = 82) and from healthy controls (n = 72). The frequencies of CD4+CD25high T-cells were quantified using flow cytometry, and function was assessed by the ability to suppress proliferation of CD4+CD25- T-cells. Paired blood and synovial fluid was analysed from a small number of RA and reactive arthritis patients. RESULTS: There was a smaller proportion of CD4+CD25high T-cells in the peripheral blood of early active RA patients (mean 4.25%) than in patients with reactive arthritis or in controls (mean 5.90 and 5.30%, respectively, P = 0.001 in each case). Frequencies in stable, well-controlled RA (mean 4.63%) were not significantly different from early active RA or controls. There were no differences in suppressor function between groups. Higher frequencies of CD4+CD25high T-cells were found in synovial fluid than blood in both RA and reactive arthritis. CONCLUSIONS: These data demonstrate a smaller CD4+CD25high regulatory T-cell population in peripheral blood of individuals with early active RA prior to disease-modifying treatment. This may be a contributory factor in the susceptibility to RA and suggests novel approaches to therapy.

Adult↗
PubMed2006

An international study on starting tumour necrosis factor-blocking agents in ankylosing spondylitis.

OBJECTIVES: To determine the type and proportion of patients with ankylosing spondylitis who rheumatologists consider to be candidates for treatment with tumour necrosis factor (TNF)-blocking agents, and to what extent this is in agreement with the ASsessment in Ankylosing Spondylitis (ASAS) international working group recommendations on initiation of treatment with anti-TNF agents. METHODS: Participants were rheumatologists from 10 different countries, who were considered to be experts in treating patients with ankylosing spondylitis and in the use of anti-TNF treatment, but were unaware of the ASAS recommendations (unpublished at the time of study in 2003). The first 10 consecutive patients with ankylosing spondylitis seen by the rheumatologist were evaluated as to whether the patient was a candidate for anti-TNF treatment. Thereafter, a metrologist assessed the patient for disease activity and severity, and collected data on demographics and treatment. RESULTS: Complete data were available for 1207 of the 1284 patients and were used for analysis. Overall, the rheumatologists indicated that they would initiate TNF-blocking agents in 49.3% of patients, ranging from 37.2% patients in Canada to 78.3% in Australia. These candidates had higher disease activity, higher levels of acute-phase reactants, worse spinal mobility, worse function, more often hip involvement and a higher prevalence of sick leave. Of all patients considered to be candidates, 40% did not fulfil ASAS recommendations with respect to previous use of non-steroidal anti-inflammatory drugs (NSAIDs; at least two NSAIDs) or Bath Ankylosing Spondylitis Disease Activity Index (>or=4). Conversely, 36% of patients who did not fulfil the NSAID or BASDAI recommendations were still considered to be candidates for TNF-blocking treatment. OBJECTIVE: variables, such as C reactive protein, erythrocyte sedimentation rate or magnetic resonance activity, were considered less important than disease activity in the decision on starting TNF-blocking drugs. The only important objective criterion was rapid radiographic progression. CONCLUSION: Rheumatologists wanted to initiate TNF-blocking drugs in roughly half of the patients with ankylosing spondylitis. However, there was a wide variation across countries and doctors. Rheumatologists considered both disease activity and severity to be determinants of starting TNF blockers, but their decision was often in disagreement with ASAS recommendations.

Adult↗
PubMed2006

EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To formulate EULAR recommendations for the management of early arthritis. METHODS: In accordance with EULAR's "standardised operating procedures", the task force pursued an evidence based approach and an approach based on expert opinion. A steering group comprised of 14 rheumatologists representing 10 European countries. The group defined the focus of the process, the target population, and formulated an operational definition of "management". Each participant was invited to propose issues of interest regarding the management of early arthritis or early rheumatoid arthritis. Fifteen issues for further research were selected by use of a modified Delphi technique. A systematic literature search was carried out. Evidence was categorised according to usual guidelines. A set of draft recommendations was proposed on the basis of the research questions and the results of the literature search.. The strength of the recommendations was based on the category of evidence and expert opinion. RESULTS: 15 research questions, covering the entire spectrum of "management of early arthritis", were formulated for further research; and 284 studies were identified and evaluated. Twelve recommendations for the management of early arthritis were selected and presented with short sentences. The selected statements included recognition of arthritis, referral, diagnosis, prognosis, classification, and treatment of early arthritis (information, education, non-pharmacological interventions, pharmacological treatments, and monitoring of the disease process). On the basis of expert opinion, 11 items were identified as being important for future research. CONCLUSIONS: 12 key recommendations for the management of early arthritis or early rheumatoid arthritis were developed, based on evidence in the literature and expert consensus.

Antirheumatic Agents↗
PubMed2006

Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate.

OBJECTIVE: To establish the safety and efficacy of repeat infusions of tocilizumab (previously known as MRA), a humanized anti-interleukin-6 (IL-6) receptor antibody, alone and in combination with methotrexate (MTX), for the treatment of rheumatoid arthritis (RA). METHODS: The study group comprised 359 patients with active RA in whom the response to MTX was inadequate. During a stabilization period, these patients received their current dose of MTX for at least 4 weeks. Following stabilization, they were randomized to 1 of 7 treatment arms, as follows: tocilizumab at doses of 2 mg/kg, 4 mg/kg, or 8 mg/kg either as monotherapy or in combination with MTX, or MTX plus placebo. RESULTS: A 20% response (improvement) according to the American College of Rheumatology criteria (ACR20 response) was achieved by 61% and 63% of patients receiving 4 mg/kg and 8 mg/kg of tocilizumab as monotherapy, respectively, and by 63% and 74% of patients receiving those doses of tocilizumab plus MTX, respectively, compared with 41% of patients receiving placebo plus MTX. Statistically significant ACR50 and ACR70 responses were observed in patients receiving combination therapy with either 4 mg/kg or 8 mg/kg of tocilizumab plus MTX (P < 0.05). A dose-related reduction in the Disease Activity Score in 28 joints was observed from week 4 onward, in all patients except those receiving monotherapy with 2 mg/kg of tocilizumab. In the majority of patients who received 8 mg/kg of tocilizumab, the C-reactive protein level/erythrocyte sedimentation rate normalized, while placebo plus MTX had little effect on these laboratory parameters. Tocilizumab was mostly well tolerated, with a safety profile similar to that of other biologic and immunosuppressive therapies. Alanine transaminase and aspartate transaminase levels followed a sawtooth pattern (rising and falling between infusions). There were moderate but reversible increases in the nonfasting total cholesterol and triglyceride levels and reversible reductions in the high-density lipoprotein cholesterol and neutrophil levels. There were 2 cases of sepsis, both of which occurred in patients who were receiving combination therapy with 8 mg/kg of tocilizumab plus MTX. CONCLUSION: These results indicate that targeted blockade of IL-6 signaling is a highly efficacious and promising means of decreasing disease activity in RA.

Antibodies, Monoclonal↗
PubMed2006

Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission: evidence from an imaging study may explain structural progression.

OBJECTIVE: More timely and effective therapy for rheumatoid arthritis (RA) has contributed to increasing rates of clinical remission. However, progression of structural damage may still occur in patients who have satisfied remission criteria, which suggests that there is ongoing disease activity. This questions the validity of current methods of assessing remission in RA. The purpose of this study was to test the hypothesis that modern joint imaging improves the accuracy of remission measurement in RA. METHODS: We studied 107 RA patients receiving disease-modifying antirheumatic drug therapy who were judged by their consultant rheumatologist to be in remission and 17 normal control subjects. Patients underwent clinical, laboratory, functional, and quality of life assessments. The Disease Activity Score 28-joint assessment and the American College of Rheumatology remission criteria, together with strict clinical definitions of remission, were applied. Imaging of the hands and wrists using standardized acquisition and scoring techniques with conventional 1.5T magnetic resonance imaging (MRI) and ultrasonography (US) were performed. RESULTS: Irrespective of which clinical criteria were applied to determine remission, the majority of patients continued to have evidence of active inflammation, as shown by findings on the imaging assessments. Even in asymptomatic patients with clinically normal joints, MRI showed that 96% had synovitis and 46% had bone marrow edema, and US showed that 73% had gray-scale synovial hypertrophy and 43% had increased power Doppler signal. Only mild synovial thickening was seen in 3 of the control subjects (18%), but no bone marrow edema. CONCLUSION: Most RA patients who satisfied the remission criteria with normal findings on clinical and laboratory studies had imaging-detected synovitis. This subclinical inflammation may explain the observed discrepancy between disease activity and outcome in RA. Imaging assessment may be necessary for the accurate evaluation of disease status and, in particular, for the definition of true remission.

Adult↗
PubMed2006

Regional variations in human patellar trabecular architecture and the structure of the proximal patellar tendon enthesis.

Proximal patellar tendinopathy occurs as an overuse injury in sport and is also characteristic of ankylosing spondylitis patients. It particularly affects the posteromedial part of the patellar tendon enthesis, although the reason for this is unclear. We investigated whether there are regional differences in the trabecular architecture of the patella or in the histology of the patellar tendon enthesis that could suggest unequal force transmission from bone to tendon. Trabecular architecture was analysed from X-rays taken with a Faxitron radiography system of the patellae of dissecting room cadavers and in magnetic resonance images of the knees of living volunteers. Structural and fractal analyses were performed on the Faxitron digital images using MatLab software. Regional differences at the enthesis in the thickness of the uncalcified fibrocartilage and the subchondral plate were evaluated histologically in cadaveric material. The radiological studies showed that the quantity of bone and the apparent trabecular thickness in the patella were greatest medially, and that in the lateral part of the patella there were fewer trabeculae which were orientated either antero-posteriorly or superiorly inferiorly. The histological study showed that the uncalcified fibrocartilage was most prominent medially and that the subchondral plate was thinner laterally. Overall, the results indicate that mechanical stress at the proximal patellar tendon enthesis is asymmetrically distributed and greater on the medial than on the lateral side. Thus, we suggest that the functional anatomy of the knee is closely related to regional variations in force transmission, which in turn relates to the posteromedial site of pathology in proximal patellar tendinopathy.

Adult↗
PubMed2006

Hearing improvement in a patient with variant Muckle-Wells syndrome in response to interleukin 1 receptor antagonism.

BACKGROUND: Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome, and neonatal onset multisystem inflammatory disease, also called chronic, infantile, neurological, cutaneous, and articular syndrome, are three hereditary autoinflammatory syndromes caused by mutations affecting the CIAS1/NALP3 gene on chromosome 1q44. The proinflammatory cytokine, interleukin 1beta, is believed to have a fundamental role in their pathogenesis. CASE REPORT: The case is described of a 59 year old white woman who presented with increasingly severe MWS-type features over a 15 year period. The response to interleukin 1beta inhibition with anakinra was dramatic, including a reduction in intracranial pressure with associated auditory improvement, as demonstrated by serial audiometry. CONCLUSIONS: The confirmed improvement in hearing after initiation of interleukin 1 receptor antagonism corroborates previous reports that specific blockade of this single cytokine reverses most of the symptoms of this group of CIAS1/NALP3 related autoinflammatory conditions, including the sensorineural deafness, which has not been previously reported.

Antirheumatic Agents↗