Katinka Albrecht

Evaluation of latent tuberculosis infection in patients with inflammatory arthropathies before treatment with TNF-α blocking drugs using a novel flow-cytometric interferon-γ release assay

OBJECTIVE To compare the efficacy of the conventional skin test and a novel flow cytometric whole blood assay in the diagnosis of latent tuberculosis infection (LTBI) in patients with rheumatological diseases evaluated for treatment with TNF-alpha-blocking agents. METHODS Prospective study of 97 consecutively enrolled patients, who were assessed for the presence of LTBI through clinical history, Mendel-Mantoux skin testing and chest X-ray. In addition, T-cell reactivity towards tuberculin (PPD, purified protein derivative) and the Mycobacterium tuberculosis-specific proteins ESAT-6 and CFP-10 was determined ex vivo using a flow cytometric whole blood assay. RESULTS After standard screening, 15% of patients receiving TNF-alpha-blocking therapy were pretreated with isoniazide (INH), another 5% of patients did not receive TNF-alpha-blocking therapy because of LTBI. PPD-reactivity in the skin was observed in 14% of patients compared with 39% with the whole blood test. Analysis of the M. tuberculosis-specific response to ESAT-6 and CFP-10 revealed positive results in 16% of patients. Using a decision tree incorporating history, chest X-ray and either skin-test or ESAT-6/CFP-10 results, 18 or 22% of the patients, respectively, were classified as latently infected with M. tuberculosis. Four patients treated with INH because of a positive skin reaction did not show reactivity to ESAT-6/CFP-10 in the whole blood assays. Another six patients not pretreated with INH because of negative skin tests would have received INH, had the results of the whole blood assay been taken into account. CONCLUSION The Mendel-Mantoux skin test has a low sensitivity and specificity for the diagnosis of LTBI in this cohort of patients, potentially resulting in both over- and under-treatment with prophylactic INH when compared with the flow cytometric analysis of whole blood T-cell reactivity to proteins specific to M. tuberculosis. Use of T-cell based in vitro tests may help to refine diagnostic testing for LTBI.

S1-Leitlinie der DGRh zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis 2012

Following the EULAR recommendations published in 2010 German guidelines for the medical treatment of rheumatoid arthritis were developed based on an update of the systematic literature search and expert consensus. Methotrexate is the standard treatment option at the time of diagnosis, preferably in combination with low dose glucocorticoids. Combined disease-modifying antirheumatic drugs (DMARD) therapy should be considered in patients not responding within 12 weeks. Treatment with biologicals should be initiated in patients with persistent high activity no later than 6 months after conventional treatment and in exceptional situations (e.g. early destruction or unfavorable prognosis) even earlier. If treatment with biologicals remains ineffective, changing to another biological is recommended after 3-6 months. In cases of long-standing remission a controlled reduction of medical treatment can be considered.

Reliability of different Doppler ultrasound quantification methods and devices in the assessment of therapeutic response in arthritis

OBJECTIVE To evaluate the metric qualities of power Doppler ultrasound (PDUS) for different quantification methods and devices in the assessment of arthritis during anti-inflammatory treatment. METHODS Twenty-four patients with active arthritis and first-time treatment with the TNF-alpha inhibitor adalimumab underwent sequential clinical, laboratory and US examination at baseline, weeks 2, 6 and 12. 2D and 3D PDUS was performed by two independent investigators. The images and movies were scored from 0 to 3 and the amount of colour pixels and voxels was calculated. In addition, the resistance index of a synovial artery was measured. Thirteen patients were examined with a second US machine. RESULTS Treatment response was already observed at week 2 with a significant reduction of 2D (P < 0.01) and 3D scores (P < 0.001). A moderate correlation to 28-joint disease activity score was found for 3D voxel count (r(s) = 0.35, P < 0.001). Interobserver agreement was kappa or ICC >or= 0.8 for all methods except the resistance index (ICC = 0.60). Intermachine agreement was kappa = 0.57 for 2D PDUS score. CONCLUSIONS The study demonstrates good to excellent interobserver and moderate intermachine reliability of different PDUS assessment methods in a longitudinal open-label study.

German guidelines for the sequential medical treatment of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs

The German Society of Rheumatology approved new German guidelines for the sequential medical treatment of rheumatoid arthritis (RA) based on the European League Against Rheumatism (EULAR) recommendations for the management of RA published in 2010. An update of the EULAR systematic literature research was performed in Medline, Embase, and Cochrane databases. Meta-analyses, controlled trials, cohort studies, and registry data addressing traditional and biologic disease-modifying antirheumatic drugs, glucocorticoids, and treatment strategies published between January 2009 and August 2011 were included. Two reviewers independently evaluated and compared the additional data that had been published after the time limit set by the EULAR recommendations. A national guideline working group developed an adapted set of recommendations. The new German guidelines were accepted by vote using an informal Delphi approach. Twelve recommendations and the resulting updated treatment algorithm were developed and approved as a practical orientation for rheumatologists. These recommendations are based on a successive treatment with traditional and biologic disease-modifying drugs depending on the individual progress of the disease and distinct patient characteristics. The German guidelines have been developed on the basis of the internationally well-recognized EULAR recommendations. In addition, more recent evidence from a systematic literature research was considered. They have been developed and approved by a group of national experts aiming at guidance for rheumatologists to reach best medical practice.

German 2012 guidelines for the sequential medical treatment of rheumatoid arthritis. Adapted EULAR recommendations and updated treatment algorithm

Following the EULAR recommendations published in 2010 German guidelines for the medical treatment of rheumatoid arthritis were developed based on an update of the systematic literature search and expert consensus. Methotrexate is the standard treatment option at the time of diagnosis, preferably in combination with low dose glucocorticoids. Combined disease-modifying antirheumatic drugs (DMARD) therapy should be considered in patients not responding within 12 weeks. Treatment with biologicals should be initiated in patients with persistent high activity no later than 6 months after conventional treatment and in exceptional situations (e.g. early destruction or unfavorable prognosis) even earlier. If treatment with biologicals remains ineffective, changing to another biological is recommended after 3-6 months. In cases of long-standing remission a controlled reduction of medical treatment can be considered.

The new 2012 German recommendations for treating rheumatoid arthritis : differences compared to the European standpoint.

The German Society for Rheumatology recently published guidelines for the sequential therapy of rheumatoid arthritis (RA). These recommendations were developed as a transition from the 2010 EULAR (EUropean League Against Rheumatism) recommendations to the national clinical practice and are based on an updated systematic literature research and expert discussion. While most EULAR recommendations have remained unchanged, some were modified based on new evidence from randomized, controlled trials, current clinical practice, or national drug approval status. The guidelines also include a treatment algorithm for sequential therapy of RA with disease-modifying agents including biologics.ZusammenfassungDie Deutsche Gesellschaft für Rheumatologie (DGRh) hat jüngst eine S1-Leitlinie zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis veröffentlicht. Die Empfehlungen beruhen auf einer Bewertung der EULAR (EUropean League Against Rheumatism) Recommendations vor dem Hintergrund der landesüblichen klinischen Praxis auf der Basis einer aktualisierten systematischen Literaturrecherche und eines Expertenurteils. Während sich viele EULAR-Empfehlungen in der deutschen Version unverändert finden, ergaben sich für einige Änderungen auf der Grundlage neuer Evidenz aus randomisierten kontrollierten Studien, derzeitiger klinischer Praxis oder des nationalen Medikamentenzulassungsstatus. Konkretisiert werden die Empfehlungen durch einen überarbeiteten Therapiealgorithmus mit Basistherapeutika einschließlich Biologika. Der vorliegende Kommentar soll – auch für englischsprachige Leser – die Gemeinsamkeiten und Unterschiede der deutschen Empfehlungen 2012 und der EULAR Recommendations von 2010 erläutern.

The new 2012 German recommendations for treating rheumatoid arthritis

The German Society for Rheumatology recently published guidelines for the sequential therapy of rheumatoid arthritis (RA). These recommendations were developed as a transition from the 2010 EULAR (EUropean League Against Rheumatism) recommendations to the national clinical practice and are based on an updated systematic literature research and expert discussion. While most EULAR recommendations have remained unchanged, some were modified based on new evidence from randomized, controlled trials, current clinical practice, or national drug approval status. The guidelines also include a treatment algorithm for sequential therapy of RA with disease-modifying agents including biologics.ZusammenfassungDie Deutsche Gesellschaft für Rheumatologie (DGRh) hat jüngst eine S1-Leitlinie zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis veröffentlicht. Die Empfehlungen beruhen auf einer Bewertung der EULAR (EUropean League Against Rheumatism) Recommendations vor dem Hintergrund der landesüblichen klinischen Praxis auf der Basis einer aktualisierten systematischen Literaturrecherche und eines Expertenurteils. Während sich viele EULAR-Empfehlungen in der deutschen Version unverändert finden, ergaben sich für einige Änderungen auf der Grundlage neuer Evidenz aus randomisierten kontrollierten Studien, derzeitiger klinischer Praxis oder des nationalen Medikamentenzulassungsstatus. Konkretisiert werden die Empfehlungen durch einen überarbeiteten Therapiealgorithmus mit Basistherapeutika einschließlich Biologika. Der vorliegende Kommentar soll – auch für englischsprachige Leser – die Gemeinsamkeiten und Unterschiede der deutschen Empfehlungen 2012 und der EULAR Recommendations von 2010 erläutern.

Linking systemic angiogenic factors (VEGF, angiogenin, TIMP-2) and Doppler ultrasound to anti-inflammatory treatment in rheumatoid arthritis

OBJECTIVE To evaluate an association between synovial Doppler flow and serum levels of vascular endothelial growth factor (VEGF), angiogenin and TIMP-2 in patients with rheumatoid arthritis during anti-inflammatory treatment with glucocorticoids and TNF-α inhibitors. METHODS Inflamed wrists of 15 patients with rheumatoid arthritis (RA) were examined by two independent ultrasound investigators prior to and at days 3, 7, 14 and 42 after the initiation of treatment with glucocorticoids in therapy-naïve patients or after the beginning of a therapy with a TNF-α inhibitor in patients with DMARD failure. Quantitative three-dimensional power Doppler ultrasonographic assessment of synovial vascularization was compared at each visit with serum levels of VEGF, angiogenin and TIMP-2. RESULTS In the glucocorticoid group, synovial Doppler signals decreased significantly at day 3 (-44%; P=0.003) in comparison to a delayed decrease in the TNF-α inhibitor group after 6 weeks (-46%; P=0.001). A significant reduction of serum VEGF levels could be determined with a delay of 1 week after the decrease of Doppler activity but no correlation was found between both parameters (rho: P=0.7; r=-0.03). Angiogenin concentrations decreased in the TNF group and increased in the GC group. Levels of TIMP-2 did not change significantly in both groups. CONCLUSION The decrease of serum VEGF levels under treatment with glucocorticoids or TNF-α inhibitors followed the reduction of the intra-articular synovial Doppler flow. This result supports the idea that the reduction of synovial perfusion due to anti-inflammatory treatment is not regulated by systemic VEGF, but that the inflamed joints are the source for circulating VEGF.

Poor prognostic factors guiding treatment decisions in rheumatoid arthritis patients: a review of data from randomized clinical trials and cohort studies

Prognostic factors are used for treatment decisions in rheumatoid arthritis (RA). High disease activity, the early presence of erosions, and autoantibody positivity are the most frequently used poor prognostic factors but other features, such as functional disability, extraarticular disease, or multibiomarkers, are also assessed. Prognostic factors are incorporated in current treatment recommendations for the management of RA and are used as inclusion criteria in randomized controlled trials. They are defined heterogeneously and the relevance of a single or combined presence of poor prognostic factors remains unclear. This review summarizes the current definitions of poor prognostic factors and their use in clinical research. Perspectives on future research are also outlined.

Systematische Literaturrecherche für die S1-Leitlinie zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis

BACKGROUND On behalf of the German association of Rheumatology national experts developed guidelines for the medical treatment of rheumatoid arthritis (RA) based on the EULAR recommendations for the management of RA published in 2010. Current evidence was provided with an update of the systematic literature review (SLR). The methods and results of the SLR are presented in this article. MATERIALS AND METHODS An update of the EULAR SLR for the medical treatment of RA was performed from January 2009 to August 2011. The SLR assessed all controlled studies dealing with the outcome in clinical aspects, function and structure of disease modifying treatment of RA. RESULTS Out of 6,869 screened publications, 138 articles and 56 abstracts were considered in the development of the German guidelines on the treatment of RA. A modified set of recommendations was approved in a consensus of national experts. CONCLUSION A systematic literature research provided current evidence for the German recommendations on the sequential medical treatment of RA.