TY  - JOUR
A1  - Groeber, Florian
A1  - Schober, Lena
A1  - Schmid, Freia F.
A1  - Traube, Andrea
A1  - Kolbus-Hernandez, Silvia
A1  - Daton, Karolina
A1  - Hoffmann, Sebastian
A1  - Petersohn, Dirk
A1  - Schaefer-Korting, Monika
A1  - Walles, Heike
A1  - Mewes, Karsten R.
T1  - Catch-up validation study of an in vitro skin irritation test method based on an open source reconstructed epidermis (phase II)
JF  - Toxicology in Vitro
N2  - To replace the Draize skin irritation assay (OECD guideline 404) several test methods based on reconstructed human epidermis (RHE) have been developed and were adopted in the OECD test guideline 439. However, all validated test methods in the guideline are linked to RHE provided by only three companies. Thus,the availability of these test models is dependent on the commercial interest of the producer. To overcome this limitation and thus to increase the accessibility of in vitro skin irritation testing, an open source reconstructed epidermis (OS-REp) was introduced. To demonstrate the capacity of the OS-REp in regulatory risk assessment, a catch-up-validation study was performed. The participating laboratories used in-house generated OS-REp to assess the set of 20 reference substances according to the performance standards amending the OECD test guideline 439. Testing was performed under blinded conditions. The within-laboratory reproducibility of 87% and the inter-laboratory reproducibility of 85% prove a high reliability of irritancy testing using the OS-REp protocol. In addition, the prediction capacity was with an accuracy of 80% comparable to previous published RHE based test protocols. Taken together the results indicate that the OS-REp test method can be used as a standalone alternative skin irritation test replacing the OECD test guideline 404.
KW  - Model
KW  - Chemicals
KW  - Assay
KW  - Episkin
KW  - Vivo
KW  - RHE
KW  - In vitro skin irritation testing
KW  - Open source reconstructed epidermis
KW  - Validation
KW  - Alternative test methods
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187311
VL  - 36
ER  - 
TY  - JOUR
A1  - Rech, Juergen
A1  - Hueber, Axel J.
A1  - Finzel, Stephanie
A1  - Englbrecht, Matthias
A1  - Haschka, Judith
A1  - Manger, Bernhard
A1  - Kleyer, Arnd
A1  - Reiser, Michaela
A1  - Cobra, Jayme Fogagnolo
A1  - Figueiredo, Camille
A1  - Tony, Hans-Peter
A1  - Kleinert, Stefan
A1  - Wendler, Joerg
A1  - Schuch, Florian
A1  - Ronneberger, Monika
A1  - Feuchtenberger, Martin
A1  - Fleck, Martin
A1  - Manger, Karin
A1  - Ochs, Wolfgang
A1  - Schmitt-Haendle, Matthias
A1  - Lorenz, Hanns-Martin
A1  - Nuesslein, Hubert
A1  - Alten, Rieke
A1  - Henes, Joerg
A1  - Krueger, Klaus
A1  - Schett, Georg
T1  - Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment
JF  - Annals of the Rheumatic Diseases
N2  - Objective 
To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. 

Methods 
MBDA scores (scale 1-100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. 

Results 
Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA-/ACPA-, moderate in patients who were MBDA+/ACPA- (33.3%) and MBDA-ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%). 

Conclusions 
MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients. 

Trial registration number EudraCT 
2009-015740-42.
KW  - Drug-free remission
KW  - Clinical remission
KW  - Validation
KW  - Synovitis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187519
VL  - 75
IS  - 9
ER  -