Implementation and role of modern musculoskeletal imaging in rheumatological practice in member countries of EULAR

Objectives: To document the current training, implementation and role of modern musculoskeletal imaging techniques, i.e. ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) among rheumatologists in the member countries of the European League Against Rheumatism (EULAR). Methods: English-language questionnaires for each imaging modality developed by a EULAR Taskforce were sent out to national and international scientific societies as well as imaging experts in the given modalities involved in research and/or training. The surveys were distributed via an online survey tool (Surveymonkey®). Simple descriptive and summary statistics were calculated from the responses. Results: More than 90% of US experts reported the availability of an US unit in their department. Suspicion of rheumatoid arthritis and spondyloarthritides were the main clinical indications for performing US for diagnostic purposes. Suspicion of sacroiliitis and degenerative spine disease were the most common indications to request MRI or CT for diagnostic purposes, while PET was mainly requested to diagnose large vessel vasculitis and to investigate fever of unknown origin. The reported percentage of rheumatologists performing US was highly variable, ranging from more than 80% in 6% of countries to less than 10% in 15% of countries. The majority of experts (77%) reported that their national rheumatology societies organize US courses, while courses in MRI or CT organized by the national rheumatology societies were less commonly reported (29% and 8% respectively). Conclusions: Rheumatologists in Europe utilise modern imaging techniques, however access to the techniques and training offered is varied

The effect of immunomodulators on the immunogenicity of TNF-blocking therapeutic monoclonal antibodies: a review

Therapeutic monoclonal antibodies have revolutionized the treatment of various inflammatory diseases. Immunogenicity against these antibodies has been shown to be clinically important: it is associated with shorter response duration because of diminishing concentrations in the blood and with infusion reactions. Concomitant immunomodulators in the form of methotrexate or azathioprine reduced the immunogenicity of therapeutic antibodies in rheumatoid arthritis, Crohn disease, and juvenile idiopathic arthritis. The occurrence of adverse events does not increase when immunomodulators are added to therapeutic antibodies. The mechanism whereby methotrexate and azathioprine influence immunogenicity remains unclear. Evidence-based consensus on prescribing concomitant immunomodulators is needed

Folate Receptor beta as a Potential Delivery Route for Novel Folate Antagonists to Macrophages in the Synovial Tissue of Rheumatoid Arthritis Patients

Objective. To determine the expression of folate receptor beta (FR beta) in synovial biopsy tissues and peripheral blood lymphocytes from rheumatoid arthritis (RA) patients and to identify novel folate antagonists that are more selective in the targeting and internalization of FR beta than methotrexate (MTX). Methods. Immunohistochemistry and computer-assisted digital imaging analyses were used for the detection of FR beta protein expression on immunocompetent cells in synovial biopsy samples from RA patients with active disease and in noninflammatory control synovial tissues. FR beta messenger RNA (mRNA) levels were determined by reverse transcription-polymerase chain reaction analysis. Binding affinities of FR beta for folate antagonists were assessed by competition experiments for 3 H-folic acid binding on FR beta-transfected cells. Efficacy of FR beta-mediated internalization of folate antagonists was evaluated by assessment of antiproliferative effects against FR beta-transfected cells. Results. Immunohistochemical staining of RA synovial tissue showed high expression of FR beta on macrophages in the intimal lining layer and synovial sublining, whereas no staining was observed in T cell areas or in control synovial tissue. Consistently, FR beta mRNA levels were highest in synovial tissue extracts and RA monocyte-derived macrophages, but low in peripheral blood T cells and monocytes. Screening of 10 new-generation folate antagonists revealed 4 compounds for which FR beta had a high binding affinity (20-77-fold higher than for MTX). One of these, the thymidylate synthase inhibitor BCG 945, displayed selective targeting against FR beta-transfected cells. Conclusion. Abundant FRP beta expression on activated macropliages in synovial tissue from RA patients deserves further exploration for selective therapeutic interventions with high-affinity-binding folate antagonists, of which BCG 945 may be a prototypical representative