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Paul Emery

Publications and source records attributed to Paul Emery.

At least 73 records · Page 4Linked to original sources
PubMed2004

Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial.

OBJECTIVE: To compare the benefits of initiating treatment with methotrexate (MTX) and infliximab (anti-tumor necrosis factor alpha [anti-TNFalpha] monoclonal antibody) with those of MTX treatment alone in patients with rheumatoid arthritis (RA) of < or =3 years' duration. METHODS: RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFalpha inhibitor. One thousand forty-nine patients were randomly assigned in a 4:5:5 ratio to 3 treatment groups: MTX-placebo, MTX-3 mg/kg infliximab, and MTX-6 mg/kg infliximab. MTX dosages were rapidly escalated to 20 mg/week, and infliximab or placebo infusions were given at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. RESULTS: At week 54, the median percentage of American College of Rheumatology improvement (ACR-N) was higher for the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than for the MTX-placebo group (38.9% and 46.7% versus 26.4%, respectively; P < 0.001 for both comparisons). Patients in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone (mean +/- SD changes in van der Heijde modification of the total Sharp score at week 54: 0.4 +/- 5.8 and 0.5 +/- 5.6 versus 3.7 +/- 9.6, respectively; P < 0.001 for each comparison). In addition, physical function improved significantly more in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than in the MTX-placebo group. Infliximab therapy was associated with a significantly higher incidence of serious infections, especially pneumonia. CONCLUSION: For patients with active RA in its early stages, combination therapy with MTX and infliximab provides greater clinical, radiographic, and functional benefits than treatment with MTX alone.

Adult↗
PubMed2004

Imaging in early arthritis.

Imaging can play a vital role in the evaluation of patients with early arthritis. Various imaging methods can be utilized to aid with diagnosis, predict prognosis and follow disease progression and treatment response. Previously, conventional radiography was the principal method used to evaluate and follow bone damage in patients with inflammatory arthritis. More recently the use of magnetic resonance imaging and ultrasonography has gained wider acceptance and popularity due to the ability of these multiplanar techniques to image both bone changes and soft tissue abnormalities, including synovitis. This chapter discusses the current imaging modalities used in the evaluation of patients with early arthritis, as well as the use of imaging in establishing the extent of disease, in prognosis and in monitoring disease course. Current data on imaging of patients with early arthritis due to rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis is reviewed.

Arthritis, Psoriatic↗
PubMed2004

Noninvasive techniques for assessing skeletal changes in inflammatory arthritis: imaging technique.

New imaging techniques such as ultrasound and MRI are likely to play increasing roles in the future management of patients with inflammatory arthritis, particularly those with rheumatoid arthritis and spondyloarthropathies. Ultrasound has a number of distinct advantages including its ability to scan multiple joints, safety, and immediately availability in clinic. MRI, however, is more sensitive and has a greater field of view because of its tomographic nature. Both modalities have the added advantage over radiography in that they can image soft tissue as well as bone. Dual X-ray absorptiometry already has an established role to play in the assessment of osteoporosis, but new techniques such as digital radiogrametry, quantitative CT, and ultrasound potentially will have a more important role to play in the future.

Absorptiometry, Photon↗
PubMed2004

Autologous stem cell transplantation for systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is responsive to treatment with immunosuppressives and steroids, but often pursues a relapsing or refractory course resulting in increasing incapacity and reduced survival. Autologous stem cell transplantation (ASCT) following immunoablative chemotherapy is a newer therapy for autoimmune disease of potential use in severe SLE. A retrospective registry survey was carried out by the European Blood and Marrow Transplant and European League Against Rheumatism (EBMT/EULAR) registry. Data was collected from 53 patients with SLE treated by ASCT in 23 centres. Disease duration before ASCT was 59 (2-155) months (median, range), 44 (83%) were female, and median age was 29 (9-52) years. At the time of ASCT a median of seven American College of Rheumatology (ACR) diagnostic criteria for SLE were present (range 2-10) and 33 (62%) had nephritis. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor in 93% of cases. Ex vivo CD34 stem cell selection was performed in 42% of patients. Conditioning regimens employed cyclophosphamide in 84%, anti-thymocyte globulin in 76% and lymphoid irradiation in 22%. The mean duration of follow-up after ASCT was 26 (0-78) months. Remission of disease activity (SLEDAI < 3) was seen in 33/50 (66%; 95%CI 52-80) evaluable patients by six months, of which 10/31 (32%; 95%CI 15-50) subsequently relapsed after six (3-40) months. Relapse was associated with negative anti-double stranded DNA (anti-dsDNA) antibodies before ASCT (P = 0.007). There were 12 deaths after 1.5 (0-48) months, of which seven (12%; 95%CI 3-21) were related to the procedure. Mortality was associated with a longer disease course before ASCT (P = 0.036). In conclusion, this registry study demonstrates the efficacy of ASCT for remission induction of refractory SLE, although mortality appeared high. The safety of this procedure is likely to be improved by patient selection and choice of conditioning regimen. The return of disease activity in one-third of patients might be reduced by long-term immunosuppressive therapy post-ASCT.

Adolescent↗
PubMed2004

Review of health economics modelling in rheumatoid arthritis.

As the cost of drug treatment for rheumatoid arthritis (RA) constitutes only a small proportion of total costs of the disease to individuals and society, therapeutic interventions have the potential for significant economic benefit. To take advantage of this potential, clinicians need to gain a global, long-term perspective on patient care. Economic evaluations of RA therapies are critically important in influencing decisions regarding the role of costly, but highly effective new therapies, particularly in settings where there are financial constraints on healthcare provisions. Such evaluations, therefore, need to be methodologically similar with valid results to enhance their value to clinicians and policy decision-makers. This requires the use of appropriate elements in the numerator (i.e. total number of dollars spent on healthcare as a result of the intervention) and the denominator (net health effectiveness) components of the cost-effectiveness equation. Other important design factors also need to be managed properly to ensure validity of the evaluation. In this regard, the guidelines proposed by the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Task Force represent a useful approach to help create common standards for economic evaluations in RA. Recently, the development of a number of decision analysis models in RA has helped predict the likely cost-effectiveness of new interventions such as the anti-tumour necrosis factor (TNF)-alpha agents, etanercept and infliximab, both of which have been found to be cost-effective relative to other disease-modifying anti-rheumatic drugs (DMARDs) using short-term efficacy endpoints. In comparisons of these two agents in patients with DMARD-resistant RA, etanercept has been shown to be more cost-effective than the combination of methotrexate and infliximab, administered in various dosages, over a period of 1 year using American College of Rheumatology (ACR) response rates as the primary efficacy measure. However, the criteria for determining clinical efficacy is paramount and other studies that use radiographic progression as a measure of clinical effectiveness show no difference between etanercept and infliximab in clinical efficacy. Important issues that need to be considered in developing economic models in RA include consideration of the connection between the prevention of radiographic progression and downstream economic consequences, and the need to employ lifetime models wherever possible because a long time period is necessary to determine the true cost-effectiveness of agents that modify radiographic progression of RA, such as etanercept, infliximab, and adalimumab. In doing so, it is hoped that such studies will provide optimal information to facilitate important decisions on resource allocation.

Antirheumatic Agents↗
PubMed2004

Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR.

OBJECTIVE: Since 1996, autologous hemopoietic stem cell transplantation (HSCT) has been used to treat severe rheumatoid arthritis (RA). To date, published reports have been individual cases or series containing small numbers. This study combined the worldwide experience in a single analysis. METHODS: The Autoimmune Disease Databases of the European Group for Blood and Marrow Transplantation (EBMT) and the Autologous Blood and Marrow Transplant Registry (ABMTR) were used to identify patients with RA treated with autologous HSCT. Further information relating to patient and treatment-specific variables was obtained by questionnaire. RESULTS: Seventy-six patients were registered from 15 centers. Seventy-three patients had received autologous HSCT, and in 3 patients hematopoietic stem cells (HSC) were mobilized but not transplanted. Transplanted patients (median age 42 yrs, 74% female, 86% rheumatoid factor positive) had been previously treated with a mean of 5 (range 2-9) disease modifying antirheumatic drugs (DMARD). Significant functional impairment was present, with a median Health Assessment Questionnaire (HAQ) score of 1.4 (range 1.1-2.0) and Steinbrocker score mean 2.39 (SD 0.58). The high dose treatment regimen was cyclophosphamide (CYC) alone in the majority of patients, mostly 200 mg/kg (n = 62). Seven patients received anti-thymocyte globulin (ATG) in addition to CYC, 2 patients busulfan and CYC (BuCYC), and one patient CYC with total body irradiation and ATG. One patient received fludarabine with ATG. Following treatment, one patient received bone marrow but the rest received chemotherapy and/or granulocyte colony-stimulating factor mobilized peripheral blood stem cells. The harvest was unmanipulated in 28 patients, the rest receiving some form of lymphocyte depletion, mostly through CD34+ selection. Median followup was 16 months (range 3-55). Responses were measured using the American College of Rheumatology (ACR) criteria. Forty-nine patients (67%) achieved at least ACR 50% response at some point following transplant. There was a significant reduction in the level of disability measured by the HAQ (p < 0.005). Most patients restarted DMARD within 6 months for persistent or recurrent disease activity, which provided disease control in about half the cases. Response was significantly related to seronegative RA (p = 0.02) but not to duration of disease, number of previous DMARD, presence of HLA-DR4, or removal of lymphocytes from the graft. There was no direct transplant related mortality, although one patient, treated with the BuCYC regimen, died 5 months post-transplant from infection and incidental non-small cell lung cancer. CONCLUSION: Autologous HSCT is a relatively safe form of salvage treatment in severe, resistant RA. In these open label studies significant responses were achieved in most patients, with over 50% achieving an ACR 50 or more response at 12 months. Although the procedure is not curative, recurrent or persistent disease activity may be subsequently controlled in some patients with DMARD. Clinical trials are necessary to develop this approach in patients with aggressive disease who have failed conventional treatment including anti-tumor necrosis factor agents.

Adult↗
PubMed2004

The efficacy of leflunomide monotherapy in rheumatoid arthritis: towards the goals of disease modifying antirheumatic drug therapy.

This expert review of results from the leflunomide phase II and III clinical trials database demonstrates that leflunomide meets all 3 goals desired of disease modifying antirheumatic drug (DMARD) therapy: reducing the signs and symptoms of the disease; inhibiting structural damage; and improving physical function. Further, leflunomide has a rapid onset of action, sustained efficacy, and is effective in early and late disease, regardless of whether patients have received other DMARD previously. The consistent efficacy of leflunomide across phase III clinical trials is confirmed by the findings from clinical practice. Experts agreed that it is important to observe a patient under leflunomide monotherapy for at least 3-4 months before assessing efficacy. It is possible to start maintenance therapy, with either a daily dose of leflunomide 10 mg, subsequently changing to 20 mg, or the reverse. The decision to use a loading dose when initiating leflunomide therapy depends primarily on the balance between the tolerability and rapid efficacy associated with a loading dose, and the balance desired for an individual patient. In general, the use of both maintenance and loading doses requires a flexible approach to the treatment of rheumatoid arthritis. During the first few weeks of leflunomide therapy, patient dropout can be avoided by using prednisolone rather than a loading dose. Moreover, to ensure good tolerability and compliance in patients receiving a loading dose, information and adequate support should be provided throughout treatment.

Administration, Oral↗
PubMed2004

Leflunomide: a manageable safety profile.

The safety profile of leflunomide in the treatment of rheumatoid arthritis has been well documented in clinical trials, postmarketing surveillance, and epidemiological studies. Both postmarketing surveillance and epidemiological study results are consistent with the safety profile of leflunomide reported in clinical trials, and no increased risk was observed with leflunomide, compared with other disease modifying antirheumatic drugs; these studies have allowed a more precise representation of the incidence of adverse events occurring with leflunomide under normal conditions of care. The most common leflunomide-associated adverse events include diarrhea, elevated liver enzymes, alopecia, and rash. Ninety-five percent of the Expert Panel considered the adverse events associated with leflunomide to be manageable. If an adverse event required treatment to be stopped, many of the experts would consider subsequently restarting leflunomide. For minor adverse events, it was suggested that the physician might also consider using cholestyramine or charcoal to determine if the side effect is dose-related and, if it was, reduce the leflunomide dose accordingly. In addition to informing patients about the likelihood of side effects, it is important to emphasize that their incidence appears to diminish with continued treatment. It is also important to adequately support patients who are experiencing side effects and involve them in their disease management, for example, by offering the choice of reducing the leflunomide dose and/or having symptomatic treatment. Other patient management recommendations in this review reflect the views of the majority of participants as expressed in the meeting.

Arthritis, Rheumatoid↗
PubMed2004

Lefunomide in combination therapy.

In most studies of disease modifying antirheumatic drug therapy, in combination with either leflunomide or biological agents, patients are given an additional agent after they have failed treatment with methotrexate (MTX). This review of clinical studies shows that leflunomide is clinically efficacious and well tolerated when added to either sulfasalazine or MTX, as both an initial and ongoing treatment for rheumatoid arthritis (RA). Experience in combining leflunomide with biological agents is limited to a small number of open-label studies with infliximab. According to the opinion obtained at an International Expert Panel Meeting held in Paris in May 2003, leflunomide can be used in combination therapy: 61% of the Expert Panel would use leflunomide with MTX, 71% with sulfasalazine, 43% with infliximab, 33% with adalimumab, 19% with etanercept, and 38% with anakinra. The Expert Panel stated that the combination of leflunomide and infliximab warrants a prospective, randomized, controlled trial in patients with incomplete clinical responses to leflunomide monotherapy, provided leflunomide is started first, without a loading dose, and infliximab is added after good tolerability to leflunomide has been established. The Expert Panel concluded that combination therapy with leflunomide has a place in the treatment of RA. Caution is advised, however, when using combination treatments and, therefore, the patient's safety should be carefully monitored.

Antibodies, Monoclonal↗
PubMed2003

Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig.

BACKGROUND: Effective new therapies are needed for rheumatoid arthritis. Current therapies target the products of activated macrophages; however, T cells also have an important role in rheumatoid arthritis. A fusion protein--cytotoxic T-lymphocyte-associated antigen 4-IgG1 (CTLA4Ig)--is the first in a new class of drugs known as costimulation blockers being evaluated for the treatment of rheumatoid arthritis. CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells, blocking the engagement of CD28 on T cells and preventing T-cell activation. A preliminary study showed that CTLA4Ig may be effective for the treatment of rheumatoid arthritis. METHODS: We randomly assigned patients with active rheumatoid arthritis despite methotrexate therapy to receive 2 mg of CTLA4Ig per kilogram of body weight (105 patients), 10 mg of CTLA4Ig per kilogram (115 patients), or placebo (119 patients) for six months. All patients also received methotrexate therapy during the study. The clinical response was assessed at six months with use of the criteria of the American College of Rheumatology (ACR), which define the response according to its extent: 20 percent (ACR 20), 50 percent (ACR 50), or 70 percent (ACR 70). Additional end points included measures of the health-related quality of life. RESULTS: Patients treated with 10 mg of CTLA4Ig per kilogram were more likely to have an ACR 20 than were patients who received placebo (60 percent vs. 35 percent, P<0.001). Significantly higher rates of ACR 50 and ACR 70 responses were seen in both CTLA4Ig groups than in the placebo group. The group given 10 mg of CTLA4Ig per kilogram had clinically meaningful and statistically significant improvements in all eight subscales of the Medical Outcomes 36-Item Short-Form General Health Survey. CTLA4Ig was well tolerated, with an overall safety profile similar to that of placebo. CONCLUSIONS: In patients with active rheumatoid arthritis who were receiving methotrexate, treatment with CTLA4Ig significantly improved the signs and symptoms of rheumatoid arthritis and the health-related quality of life. CTLA4Ig is a promising new therapy for rheumatoid arthritis.

Abatacept↗
PubMed2003

Elucidation of the relationship between synovitis and bone damage: a randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis.

OBJECTIVE: To simultaneously image bone and synovium in the individual joints characteristically involved in early rheumatoid arthritis (RA). METHODS: Forty patients with early, untreated RA underwent gadolinium-enhanced magnetic resonance imaging (MRI) of the second through fifth metacarpophalangeal joints of the dominant hand at presentation, 3 months, and 12 months. In the first phase (0-3 months), patients were randomized to receive either methotrexate alone (MTX) or MTX and intraarticular corticosteroids (MTX + IAST) into all joints with clinically active RA. The MTX-alone group received no further corticosteroids until the second phase (3-12 months), when both groups received standard therapy. RESULTS: In the first phase, MTX + IAST reduced synovitis scores more than MTX alone. There were significantly fewer joints with new erosions on MRI in the former group compared with the latter. During the second phase, the synovitis scores were equivalent and a similar number of joints in each group showed new erosions on MRI. In both phases, there was a close correlation between the degree of synovitis and the number of new erosions, with the area under the curve for MRI synovitis the only significant predictor of bone damage progression. In individual joints, there was a threshold effect on new bone damage related to the level of synovitis; no erosions occurred in joints without synovitis. CONCLUSION: In early RA, synovitis appears to be the primary abnormality, and bone damage occurs in proportion to the level of synovitis but not in its absence. In the treatment of patients with RA, outcome measures and therapies should focus on synovitis.

Adrenal Cortex Hormones↗
PubMed2003

Role of metacarpophalangeal joint anatomic factors in the distribution of synovitis and bone erosion in early rheumatoid arthritis.

OBJECTIVE: To investigate the role of metacarpophalangeal (MCP) joint anatomic and biomechanical factors in the distribution of synovitis and bone erosion in early rheumatoid arthritis (RA). METHODS: Thirty-three patients with early RA with clinically diagnosed MCP joint disease and 28 healthy controls were examined by magnetic resonance imaging of the second to fifth MCP joints of the dominant hand. T1 and T2 fat-suppressed coronal sequences were obtained to assess erosion, and dynamic contrast-enhanced images were acquired to assess synovitis in all of the RA patients and in 8 of the controls. Erosions were defined as bone defects with sharp margins observed using T1-weighted imaging in 2 planes, with a cortical break seen in at least 1 plane. The location of erosions was recorded. The volume of synovitis surrounding each MCP joint (divided into 8 regions) was calculated by summation of voxels derived from the maximal enhancement parameters. The synovial volumes adjacent to MCP joint collateral ligaments were determined by correcting synovial volumes for the positions of asymmetrically placed flexor tendons. RESULTS: In patients with early RA in whom bone erosions were present, there was a propensity for involvement of the radial side of the second (P < 0.0001), third (P = 0.002), and fourth (P = 0.056) MCP joints, but not the fifth. Fifty-two of the 110 erosions (47.3%) occurred adjacent to the radial collateral ligaments of the second, third, and fourth MCP joints. The volume of synovitis was also greater on the radial side of the second (P < 0.0001) and third (P < 0.001) MCP joints. A predilection for synovitis in all of the MCP joints adjacent to the radial collateral ligaments was evident when the positional effects of the flexor tendon were considered. The position of radial collateral ligaments had an effect on erosion formation that was independent of synovitis. A predilection for radial bone damage was also evident in the controls, although lesions were 5-fold less frequent, were generally smaller, and had well-defined margins. CONCLUSION: This study shows that there is a predilection for both synovitis and bone erosion formation on the radial side of the MCP joints in early RA, and that joint inflammation appears to drive the inherent tendency for bone damage on the radial side of joints. These findings have implications regarding the pathogenesis of joint damage in RA.

Adult↗
PubMed2003

Prognostic factors in a large cohort of patients with early undifferentiated inflammatory arthritis after application of a structured management protocol.

OBJECTIVE: Inflammatory arthritis of the hands is a frequent clinical presentation with a variable outcome. Patients not satisfying the classification criteria for recognized arthritides are described as having undifferentiated inflammatory arthritis, for which there are no accepted therapeutic algorithms. This study assessed the clinical outcome of patients with undifferentiated arthritis of the hands after use of a treatment algorithm, and evaluated the prognostic features in these patients. METHODS: One hundred consecutive patients with undifferentiated arthritis of the hands were assessed following use of a pragmatic treatment algorithm that was based on clinical presentation and response to treatment. The following standard step-up treatment protocol was used: 1) nonsteroidal antiinflammatory drugs (NSAIDs), 2) a single dose of corticosteroid administered by either intramuscular or intraarticular injection, and 3) disease-modifying antirheumatic drugs (DMARDs). Patients with specific rheumatologic diagnoses were excluded. The primary outcome was persistence of synovitis at 12 months. RESULTS: Seventy-eight percent of patients received NSAIDs, 72% received corticosteroids, and 30% received DMARD therapy. Among patients who had synovitis at 12 months, the prevalence of rheumatoid factor (RF) seropositivity, swollen joints, and synovitis at baseline was greater than in those without persistent synovitis. Logistic regression analysis showed baseline investigations to be poor predictors of subsequent DMARD use, with the best predictor being persistence of synovitis at 12 weeks. Rheumatoid arthritis (RA) developed in 14 patients. Logistic regression analysis showed that significant predictors of RA were RF seropositivity and the painful joint count at baseline. No patient who experienced resolution of synovitis by 12 weeks had persistent synovitis that subsequently required DMARD therapy. Only 13% of patients entered remission. Early resolution of synovitis was associated with an excellent prognosis. CONCLUSION: Undifferentiated arthritis of the hands is not a benign condition, with 30% of patients receiving DMARD therapy by 12 months and low remission rates. Results of the clinical assessment at 12 weeks is the single best predictor of future therapy. This study provides background data for use in determining future therapeutic interventions.

Adolescent↗