CXCL16 is elevated in the cerebrospinal fluid versus serum and in inflammatory conditions with suspected and proved central nervous system involvement.

In neuro-inflammatory diseases, activated T cells are thought to drive the inflammatory process. In this study, we investigated the potential role of three T cell attracting chemokines (CK) in neuro-inflammation. For this purpose, we measured levels of CXCL16, CCL17 and CCL18 in matched serum and cerebrospinal fluid (CSF) samples of patients with different neurological diseases.

DAS28: a useful instrument to monitor infliximab treatment in patients with rheumatoid arthritis.

The Disease Activity Score using 28 joint counts (DAS28) has been developed in a cohort of patients with rheumatoid arthritis in which only conventional anti-rheumatic treatments were used. It has extensively been validated to monitor disease activity in daily clinical practice as well as in clinical trials. The study of Vander Cruyssen and colleagues showed that the DAS28 correlated best with the decisions of rheumatologists to increase the infliximab dose because of insufficient response.

Minimal disease activity for rheumatoid arthritis: a preliminary definition.

Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA.

Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor.

Objective: To study whether genetic variants of macrophage migration inhibitory factor (MIF), the MIF -173G>C and CATT(5-8) alleles, are associated with disease severity and levels of circulating MIF in patients with rheumatoid arthritis (RA).

Methods: Genotyping was performed in patients with early RA and in healthy controls. Demographic data, disease activity, and outcome measurements were compared between patients with and without the MIF variants.

Is the disease course of rheumatoid arthritis becoming milder? Time trends since 1985 in an inception cohort of early rheumatoid arthritis.

Objective: Based on comparisons of short-term cohort studies or cross-sectional samples of patients from different calendar times, it has been suggested that present patients with rheumatoid arthritis (RA) have a milder disease course compared with that of patients in past decades. This study was undertaken to investigate whether the course of disease activity and functional disability in patients with RA has become milder over the past several years.

Methods: We used the Nijmegen inception cohort of early RA, which included all patients with newly diagnosed RA who had attended the department of rheumatology at Radboud University Nijmegen Medical Centre since 1985.

Use of combination of leflunomide with biological agents in treatment of rheumatoid arthritis.

An Expert Panel Meeting was held in May 2004 to assess experience with combination therapy with leflunomide and biological agents in the treatment of rheumatoid arthritis (RA), to identify both optimal use of such combinations and precautions for use. Eleven published prospective or retrospective studies were reviewed, principally evaluating combination of leflunomide with infliximab, as well as patient registry data. Available data suggest that combination therapies are more efficacious than monotherapies, reflecting the complementarity of mechanisms of action.

Dermatological conditions during TNF-alpha-blocking therapy in patients with rheumatoid arthritis: a prospective study.

Various dermatological conditions have been reported during tumor necrosis factor (TNF)-alpha-blocking therapy, but until now no prospective studies have been focused on this aspect. The present study was set up to investigate the number and nature of clinically important dermatological conditions during TNF-alpha-blocking therapy in patients with rheumatoid arthritis (RA). RA patients starting on TNF-alpha-blocking therapy were prospectively followed up.

Cytokine production of stimulated whole blood cultures in rheumatoid arthritis patients receiving short-term infliximab therapy.

Patients with rheumatoid arthritis (RA) treated with anti-tumor necrosis factor (TNF) strategies have an increased susceptibility to infections, especially those caused by intracellular pathogens. In this study we assessed the cytokine production capacity in patients with RA and we further investigated whether anti-TNF therapy modulates the production of pro-inflammatory cytokines involved in the resistance against infections. Whole blood cultures from 10 RA patients and 10 healthy controls were stimulated with heat-killed Candida albicans, Salmonella typhimurium, Staphyloccocus aureus, Aspergillus fumigatus or Mycobacterium tuberculosis and production of interleukin (IL)-1beta, IL-6, IL-10, interferon (IFN)-gamma and TNF-alpha was measured.

Modeling the 5-year cost effectiveness of treatment strategies including tumor necrosis factor-blocking agents and leflunomide for treating rheumatoid arthritis in the Netherlands.

Objective: To determine the cost effectiveness of treatment strategies for rheumatoid arthritis patients satisfying the indication for tumor necrosis factor (TNF)-blocking treatment.

Methods: A Markov model study was performed. The following treatment strategies were considered: 1) usual treatment; 2) treatment with leflunomide, in the case of nonresponse after 3 months, switch to usual treatment; 3) TNF-blocking treatment, in the case of nonresponse after 3 months, switch to usual treatment; 4) treatment with leflunomide, in the case of nonresponse, switch to TNF-blocking treatment, in the case of nonresponse to TNF-blocking treatment, switch to usual treatment; 5) TNF-blocking treatment, in the case of nonresponse, switch to leflunomide treatment, in the case of nonresponse to leflunomide, switch to usual treatment.

Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma.

Objective: To study the expression of Toll-like receptor 2 (TLR-2) and TLR-4 and its association with proinflammatory cytokines in synovial tissue from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and healthy individuals.

Methods: Synovial tissue specimens from 29 RA patients were stained for TLR-2, TLR-4, and proinflammatory cytokines (interleukin-1beta [IL-1beta], IL-12, IL-17, IL-18, and tumor necrosis factor alpha [TNFalpha]). The expression of TLR-2, TLR-4, and cytokines as well as the degree of inflammation in synovial tissue were compared between patients with RA, patients with OA (n = 5), and healthy individuals (n = 3).

The relationship between disease activity and radiologic progression in patients with rheumatoid arthritis: a longitudinal analysis.

Objective: Radiologic progression in rheumatoid arthritis (RA) is considered the consequence of persistent inflammatory activity. To determine whether a change in disease activity is related to a change in radiologic progression in individual patients, we investigated the longitudinal relationship between inflammatory disease activity and subsequent radiologic progression.

Methods: The databases of the University Medical Center Nijmegen (UMCN) cohort and the Maastricht Combination Therapy in RA (COBRA) followup study cohort were analyzed.

Are better endpoints and better design of clinical trials needed?

For the clinician it is important to know whether a new drug works, and how the new drug performs against other drugs. However, new drugs are typically tested in placebo-controlled trials without active comparison. New drugs are often tested in a population with high levels of disease activity.

The Nijmegen inception cohort of early rheumatoid arthritis.

Rheumatoid arthritis is a heterogeneous chronic disease with an unpredictable disease course. To study such a disease, longterm observational studies are needed, with regular assessment of patients using valid and reproducible measures. This article describes the purpose and design of such a study at the Department of Rheumatology, University Medical Centre Nijmegen.

Efficacy and safety of leflunomide and predisposing factors for treatment response in patients with active rheumatoid arthritis: RELIEF 6-month data.

Objective: The RELIEF investigation was a 48-week, multicenter, international study comprising 2 phases. Results from the first phase, a 24-week open-label cohort study that evaluated the safety and efficacy of leflunomide, as well as predisposing factors to treatment response, are reported here.

Methods: Patients received leflunomide 100 mg once daily for 3 days, followed by 20 mg once daily thereafter.

MCID/Low Disease Activity State Workshop: summary, recommendations, and research agenda.

The OMERACT 6 Minimal Clinically Important Difference/Low Disease Activity Workshop was organized with the aim of meeting the many challenges that exist in determining a low disease activity in rheumatoid arthritis (RA). This article presents an overview of that workshop, including results of the voting, a summary of associated discussions, recommendations, and a proposed research agenda.

MCID/Low Disease Activity State Workshop: low disease activity state in rheumatoid arthritis.

The MCID (minimal clinically important difference) module of OMERACT 5 developed a research agenda that led to the conclusion that a state of low disease activity for rheumatoid arthritis (RA) would need to be defined. To develop such a definition the various concepts and terminologies, the process for developing an operational definition, and the availability and design of longitudinal datasets for validation needed to be considered. This article describes the process of the MCID/Low Disease Activity State Workshop at OMERACT 6 to develop such a definition.

Intravenous human recombinant tumor necrosis factor receptor p55-Fc IgG1 fusion protein Ro 45-2081 (lenercept): a double blind, placebo controlled dose-finding study in rheumatoid arthritis.

Objective: To determine the optimal dose regimen for intravenous Ro 45-2081 (lenercept) in patients with rheumatoid arthritis (RA) by evaluating efficacy, safety, tolerability, and pharmacokinetic and pharmacodynamic characteristics.

Methods: Adult patients with longstanding RA who were taking stable doses of nonsteroidal antiinflammatory drug and/or low dose corticosteroids but who had stopped their previous disease-modifying antirheumatic drug were randomly assigned to receive 3 intravenous infusions, one every 4 weeks, of placebo or Ro 45-2081 in a double blind, placebo controlled, parallel group multicenter trial. Patients received one of the following: (1) placebo, (2) low dose Ro 45-2081 (0.

Association of interleukin-18 expression with enhanced levels of both interleukin-1beta and tumor necrosis factor alpha in knee synovial tissue of patients with rheumatoid arthritis.

Objective: To examine the expression patterns of interkeukin-18 (IL-18) in synovial biopsy tissue of patients with rheumatoid arthritis (RA), and to determine whether expression of this primary cytokine is related to the expression of other cytokines and adhesion molecules and related to the degree of joint inflammation.

Methods: Biopsy specimens of knee synovial tissue either without synovitis (n = 6) or with moderate or severe synovitis (n = 11 and n = 12, respectively) were obtained from 29 patients with active RA. Paraffin-embedded, snap-frozen sections were used for immunohistochemical detection of IL-18, tumor necrosis factor alpha (TNFalpha), IL-1beta, IL-12, and IL-17.

Neutrophil migration and production of reactive oxygen species during treatment with a fully human anti-tumor necrosis factor-alpha monoclonal antibody in patients with rheumatoid arthritis.

Objective: To evaluate the effects of therapy with a fully human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody on the production of superoxide and other reactive oxygen species (ROS) and on the migration capacity of neutrophils in patients with rheumatoid arthritis (RA).

Methods: A total of 29 patients with active RA and 25 healthy controls participated. Assessments were performed at baseline and 2 weeks after the first administration of anti-TNF-alpha.

Tailored cognitive-behavioral therapy in early rheumatoid arthritis for patients at risk: a randomized controlled trial.

Recent developments in chronic pain research suggest that effectiveness of cognitive-behavioral therapy (CBT) may be optimized when applying early, customized treatments to patients at risk. For this purpose, a randomized, controlled trial with tailor-made treatment modules was conducted among patients with relatively early rheumatoid arthritis (RA disease duration of <8 years), who had been screened for psychosocial risk profiles. All participants received standard medical care from a rheumatologist and rheumatology nurse consultant.