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Paul Emery

Publications and source records attributed to Paul Emery.

At least 37 records · Page 2Linked to original sources
PubMed2006

A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma.

OBJECTIVE: The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence-based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in pulmonary fibrosis in SSc. METHODS: Forty-five patients were randomized to receive low-dose prednisolone and 6 infusions (monthly) of CYC followed by oral AZA, or placebo. Primary outcome measures were change in percent predicted forced vital capacity (FVC) and change in single-breath diffusing capacity for carbon monoxide (DLCO). Secondary outcome measures included changes in appearance on high-resolution computed tomography and dyspnea scores. An intent-to-treat statistical analysis was performed. RESULTS: At baseline, there were no significant group differences in factors linked to outcome, including severity of pulmonary fibrosis and autoantibody status. Sixty-two percent of the patients completed the first year of treatment. Withdrawals included 9 patients (6 from the placebo group) with significant decline in lung function, 2 with treatment side effects (both from the active treatment group), and 6 with non-trial-related comorbidity. No hemorrhagic cystitis or bone marrow suppression was observed. Estimation of the relative treatment effect (active treatment versus placebo) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19%; this between-group difference showed a trend toward statistical significance (P = 0.08). No improvements in DLCO or secondary outcome measures were identified. CONCLUSION: This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo. However, for FVC there was a trend toward statistical significance between the 2 groups. This suggests that treatment of pulmonary fibrosis in SSc with low-dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease. Therapy was well tolerated with no increase in serious adverse events.

Administration, Oral↗
PubMed2006

Ankylosing spondylitis: new treatment modalities.

Ankylosing spondylitis (AS) is a chronic and progressive inflammatory arthropathy that affects young adults. It is associated with increased morbidity and mortality, and can have a devastating effect on quality of life. Conventional therapeutic regimes have traditionally been insufficient to control symptoms and signs of disease, and have failed to halt disease progression. However, the outlook of AS has changed with the advent of biological agents that block pivotal inflammatory cytokines, such as tumour necrosis factor-alpha. Ongoing research has proven these agents to be efficacious and safe in the short and medium term. Further, longer-term trials are awaited to address the issue of whether these therapies are true disease modifiers in AS.

Adalimumab↗
PubMed2006

Analysis of Fcgamma receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B.

The Fcgamma receptors play important roles in the initiation and regulation of many immunological and inflammatory processes, and genetic variants (FCGR) have been associated with numerous autoimmune and infectious diseases. The data in rheumatoid arthritis (RA) are conflicting and we previously demonstrated an association between FCGR3A and RA. In view of the close molecular proximity with FCGR2A, FCGR2B and FCGR3B, additional polymorphisms within these genes and FCGR haplotypes were examined to refine the extent of association with RA. Biallelic polymorphisms in FCGR2A, FCGR2B and FCGR3B were examined for association with RA in two well characterized UK Caucasian and North Indian/Pakistani cohorts, in which FCGR3A genotyping had previously been undertaken. Haplotype frequencies and linkage disequilibrium were estimated across the FCGR locus and a model-free analysis was performed to determine association with RA. This was followed by regression analysis, allowing for phase uncertainty, to identify the particular haplotype(s) that influences disease risk. Our results reveal that FCGR2A, FCGR2B and FCGR3B were not associated with RA. The haplotype with the strongest association with RA susceptibility was the FCGR3A-FCGR3B 158V-NA2 haplotype (odds ratio 3.18, 95% confidence interval 1.13-8.92 [P = 0.03] for homozygotes compared with all genotypes). The association was stronger in the presence of nodules (odds ratio 5.03, 95% confidence interval 1.44-17.56; P = 0.01). This haplotype was also more common in North Indian/Pakistani RA patients than in control individuals, but not significantly so. Logistic regression analyses suggested that FCGR3A remained the most significant gene at this locus. The increased association with an FCGR3A-FCGR3B haplotype suggests that other polymorphic variants within FCGR3A or FCGR3B, or in linkage disequilibrium with this haplotype, may additionally contribute to disease pathogenesis.

Antigens, CD↗
PubMed2006

Abatacept.

New therapies, in particular the tumor necrosis factor-alpha-blocking drugs, have led to improved control of inflammation in rheumatoid arthritis for a proportion of patients. There remains a need for therapies for patients who do not respond to these drugs or in whom they are contraindicated or not tolerated. There is evidence that T cells are involved in the initiation and perpetuation of rheumatoid arthritis. Abatacept is the first in a new class of drugs targeted at T-cell function in autoimmune disease: the costimulation blockers. It has shown safety and efficacy in rheumatoid arthritis. Further trials of this and other costimulation blockers are in progress in rheumatoid arthritis and other diseases.

Abatacept↗
PubMed2006

Rituximab: novel B-cell depletion therapy for the treatment of rheumatoid arthritis.

Significant numbers of patients with rheumatoid arthritis (RA) suffer from disease that is refractory to both conventional therapy and newer biological agents such as TNF-alpha inhibitors. These patients may respond insufficiently, lose an effective response, develop toxicity or carry contraindications to such agents. Rituximab, a chimeric monoclonal antibody against CD20 that effectively depletes B cells in peripheral blood, has been licensed for the treatment of certain haematological malignancies for almost 10 years. B cells are now known to have multiple key roles in the pathogenesis of RA. Data is now available that indicates efficacy and safety of B-cell depletion with rituximab in the treatment of RA in a variety of patient groups. The clinical outcomes from these studies, together with its safety profile, have led to rituximab being licensed for the treatment of patients with RA who have failed to obtain benefit from anti-TNF-alpha agents.

Antibodies, Monoclonal↗
PubMed2005

Recommendations for musculoskeletal ultrasonography by rheumatologists: setting global standards for best practice by expert consensus.

OBJECTIVE: To establish an expert consensus of best practice for rheumatologists performing musculoskeletal ultrasonography (MUS). METHODS: A panel of worldwide experts in MUS was identified by literature review, membership of teaching faculty, and peer recommendation. They were invited to take part in a 4-stage Delphi process employing 2 iterative rounds to establish a consensus of specific indications, anatomic areas, and knowledge and skills required by rheumatologists performing MUS. RESULTS: Experts in MUS were identified (n = 57; 37 radiologists, 20 rheumatologists). Successive rounds of this rigorous Delphi exercise enabled group consensus to be achieved in 30 of the proposed 37 categories comprising 8 of 13 indications (inflammatory arthritis, tendon pathology, effusion, bursitis, monitoring disease activity, monitoring disease progression, guided aspiration, and injection), 8 of 10 anatomic areas (hand, wrist, elbow, shoulder, hip, knee, ankle and heel, and forefoot), and 14 categories of knowledge and skills (physics, anatomy, pathology, equipment, clinical application and relevance, indications and limitations, artifact, machine function and operation, patient and probe position, planes and system of examination, image optimization, dynamic assessment, color Doppler, and power Doppler). CONCLUSION: We have produced the first expert-derived, interdisciplinary consensus of recommendations for rheumatologists performing MUS. This represents a significant advance that will not only direct future rheumatology MUS practice, but will facilitate informed educational development. This is an important step towards the introduction of a specific training curriculum and assessment process to ensure competent rheumatologist ultrasonographers.

Benchmarking↗
PubMed2005

C-reactive protein as a predictor of infliximab treatment outcome in patients with rheumatoid arthritis: defining subtypes of nonresponse and subsequent response to etanercept.

OBJECTIVE: Nonresponse to anti-tumor necrosis factor alpha in patients with rheumatoid arthritis (RA) is poorly understood. The aims of this study were to define nonresponse patterns using infliximab and C-reactive protein (CRP) profiles, to assess the predictive power of a CRP response for outcome, and to correlate these findings with subsequent response to etanercept. METHODS: We studied 207 patients with resistant RA who were started on treatment with infliximab. After 12 weeks, the American College of Rheumatology 20% improvement criteria (ACR20) were used to classify patients as responders (ACR20 response or greater) or nonresponders (NRs). The NRs were further subdivided into 3 groups according to the CRP response at weeks 2, 6, and 12. Within the NR group, those with a suppressed CRP at week 12 continued taking infliximab for a further 12 weeks; those without a CRP response were switched to etanercept, and the ACR response at 12 weeks was calculated. RESULTS: At week 12, 54% of patients achieved an ACR20 response, and 46% failed to achieve a response. Of the NRs, 63% demonstrated a significant reduction in the CRP level at week 12, 59% of whom achieved an ACR20 response at week 24 on continuation of infliximab. Of the patients who did not demonstrate a significant reduction in the CRP level after the first infusion, 86% failed to show a biochemical or ACR20 response by week 12. Twenty-four percent of the NRs had a temporary reduction in the CRP level, and 13% of the NRs showed no CRP reduction. Seventy-five percent of these NRs switched to etanercept, and 68% of this group achieved an ACR20 response at week 12 (51% achieved an ACR50 response), with a CRP response in 63%. CONCLUSION: Infliximab NRs comprise subtypes with distinct CRP patterns. Failure to suppress the CRP at week 2 identified the majority of patients who were NRs at week 12. CRP suppression at week 12 in the NRs was associated with a late clinical improvement with infliximab treatment (24 weeks), whereas failure to suppress the CRP at week 12 was associated with a good response on switching to etanercept.

Antibodies, Monoclonal↗
PubMed2005

Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Anti-tumor necrosis factor alpha agents are among the most effective therapies for rheumatoid arthritis (RA). However, their optimal use is yet to be determined. This 12-month double-blind study attempted remission induction using standard therapy with or without infliximab in patients with early, poor-prognosis RA. The primary end point was synovitis (measured by magnetic resonance imaging [MRI]). Clinical observations continued to 24 months. METHODS: All patients had fewer than 12 months of symptoms. Assessments included full metrologic evaluation, laboratory tests, radiographs, functional evaluation using the Health Assessment Questionnaire (HAQ), and quality of life measurement using the RA Quality of Life (RAQoL) questionnaire. MRI was performed at 0, 4, 14, and 54 weeks; MR images were scored blindly. Patients received methotrexate (MTX) and were randomized to receive either infliximab or placebo for 12 months. RESULTS: Twenty patients were recruited (mean age 52 years, mean symptom duration 6 months, mean C-reactive protein level 42 mg/liter, and 65% rheumatoid factor positive). At 1 year, all MRI scores were significantly better, with no new erosions in the infliximab plus MTX group; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology (ACR) 50% and 70% improvement criteria (78% versus 40% in the placebo plus MTX group and 67% versus 30%, respectively) and had a greater functional benefit (P < 0.05 for all comparisons). Importantly, at 1 year after stopping induction therapy, response was sustained in 70% of the patients in the infliximab plus MTX group, with a median Disease Activity Score in 28 joints (DAS28) of 2.05 (remission range). At 2 years, there were no significant between-group differences in the DAS28, ACR response, or radiographic scores, but differences in the HAQ and RAQoL scores were maintained (P < 0.05). CONCLUSION: Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year. At 2 years, functional and quality of life benefits were sustained, despite withdrawal of infliximab therapy. These data may have significant implications for the optimal use of expensive biologic therapies.

Antibodies, Monoclonal↗
PubMed2005

Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: twelve-month results of a phase iib, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To determine the clinical efficacy, safety, and immunogenicity of abatacept (CTLA-4Ig), a selective costimulation modulator, in patients with rheumatoid arthritis (RA) that has remained active despite methotrexate (MTX) therapy. METHODS: This was a 12-month, multicenter, randomized, double-blind, placebo-controlled study. A total of 339 patients with active RA despite MTX therapy were randomly assigned to receive 10 mg/kg abatacept (n = 115), 2 mg/kg abatacept (n = 105), or placebo (n = 119). This report focuses on the results observed at month 12 of a phase IIb trial. RESULTS: A significantly greater percentage of patients treated with 10 mg/kg abatacept met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at 1 year compared with patients who received placebo (62.6% versus 36.1%; P < 0.001). Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20.2%; P < 0.001) and ACR70 responses (20.9% versus 7.6%; P = 0.003) compared with patients who received placebo. For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire scores compared with patients who received placebo (49.6% versus 27.7%; P < 0.001). Abatacept at a dosage of 10 mg/kg elicited an increase in rates of remission (Disease Activity Score in 28 joints of <2.6) compared with placebo at 1 year (34.8% versus 10.1%; P < 0.001). The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted. CONCLUSION: Abatacept was associated with significant reductions in disease activity and improvements in physical function that were maintained over the course of 12 months in patients with RA that had remained active despite MTX treatment. Abatacept was found to be well tolerated and safe over the course of 1 year. Abatacept in combination with MTX has the potential to play an important role in future RA therapy.

Abatacept↗
PubMed2005

High-resolution magnetic resonance imaging for the assessment of hand osteoarthritis.

OBJECTIVE: To investigate the use of a novel surface coil for clinically utilized magnetic resonance imaging (MRI) scanners, in order to describe the microanatomic basis for hand osteoarthritis (OA) at all stages of disease. METHODS: MRI of proximal or distal interphalangeal joints was performed in 58 subjects: 16 patients with early OA (symptom duration < or =12 months), 14 patients with chronic OA, 10 patients with clinically normal asymptomatic joints adjacent to arthritic joints, and 18 normal controls. High-resolution images were obtained with displayed pixel dimensions of 80-100 mum using a 1.5T scanner and a 23-mm-diameter surface coil. All joint structures were evaluated. RESULTS: The high-resolution images of every joint structure showed comparable abnormalities in both early and chronic OA, including cartilage loss, bone edema, synovial enhancement, osteophytosis, and erosions. Heberden's and Bouchard's node formation occurred at regions where soft tissue bulged through the capsule between the dorsal tendons and collateral ligaments (CLs). Prominent CL thickening or disruption (100% of OA patients) was evident even in joints where cartilage was partially preserved. Clinically normal joints adjacent to OA hand joints showed thickening and enhancement of CLs which was the most common abnormality seen (80% of OA patients). Older normal subjects showed subtle changes within the CLs. CONCLUSION: Obtaining high-resolution MR images from clinically utilized scanners represents a novel way for exploring the microanatomic basis of hand arthritis and may have considerable potential in the clinical setting. In the present evaluation in nodal OA, previously unappreciated CL abnormalities were especially common.

Aged↗
PubMed2005

Reduction of the efficacy of methotrexate by the use of folic acid: post hoc analysis from two randomized controlled studies.

OBJECTIVE: To examine the effect of folic acid on the efficacy of methotrexate (MTX) treatment in rheumatoid arthritis (RA) at 12 months in 2 phase III randomized controlled trials (RCTs) of leflunomide in which MTX was used as a comparator. METHODS: Analyses were restricted to patients randomized to receive MTX who had rheumatoid factor data. The US study recruited 482 patients with active RA; 179 received at least 1 dose of MTX, and all were mandated to receive 1 mg of oral folic acid once or twice daily. The multinational European study recruited 999 patients with active RA; 489 received at least 1 dose of MTX, and oral folic acid was not required, although 50 received folate after developing an adverse event. Because of similar entry criteria for both studies, the data for patients with available primary outcome data at week 52 were pooled (n = 668), and the patients were grouped by folic acid use (n = 225) and nonuse (n = 443). To account for the significant between-study differences in the MTX groups, baseline covariates were adjusted using propensity scores so that folic acid users could be matched with nonusers. This allowed for a comparison of differences in American College of Rheumatology (ACR) 20% improvement criteria at week 52. RESULTS: At study entry, non-folic acid users had a significantly lower mean body weight, shorter mean RA duration, and higher mean disease activity (measured by joint counts, patient's and physician's global assessments, and acute-phase reactant levels). The mean MTX dosage at week 52 was similar in the 2 RCTs. Using propensity score matching techniques, the proportion of patients achieving an ACR 20% response at week 52 averaged 17% higher in the non-folic acid group than in the folic acid group (range 15-21%). Similarly, the proportion of patients achieving ACR 50% and ACR 70% responses averaged 14% (range 12-16%) and 12% (range 9-14%) higher, respectively, in the non-folic acid group. Adverse events were reported in 93% of US study patients and 94% of the multinational study patients. Elevated liver transaminase levels (above the upper limit of normal) were reported in 29% of the US study patients (majority receiving folic acid) and 62% of the multinational study patients (majority not receiving folic acid). CONCLUSION: After using propensity scores to adjust for differences in the baseline characteristics of folic acid users and non-folic acid users, 9-21% fewer MTX-treated RA patients taking folic acid had ACR 20%, 50%, or 70% improvement at 52 weeks compared with those who did not receive folic acid in the 2 phase III RA clinical trials. As a post hoc analysis, the results of this data analysis should be considered "hypothesis generating" and an impetus for future studies regarding the effects of folic acid on the efficacy of MTX in RA.

Adult↗
PubMed2005

Co-stimulatory blockade as therapy for rheumatoid arthritis.

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.

Animals↗
PubMed2005

Are early arthritis clinics necessary?

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.

Ambulatory Care Facilities↗
PubMed2005

Potential for altering rheumatoid arthritis outcome.

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.

Antirheumatic Agents↗