TY  - JOUR
A1  - Goebeler, M.
A1  - Bata-Csörgő, Z.
A1  - Simone, C. de
A1  - Didona, B.
A1  - Remenyik, E.
A1  - Reznichenko, N.
A1  - Stoevesandt, J.
A1  - Ward, E. S.
A1  - Parys, W.
A1  - Haard, H. de
A1  - Dupuy, P.
A1  - Verheesen, P.
A1  - Schmidt, E.
A1  - Joly, P.
T1  - Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase II multicentre, open-label feasibility trial
JF  - British Journal of Dermatology
N2  - Background
Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. There is an unmet need for fast-acting drugs that enable patients to achieve early sustained remission with reduced corticosteroid reliance.

Objectives
To investigate efgartigimod, an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor, thereby reducing serum IgG levels, for treating pemphigus.

Methods
Thirty-four patients with mild-to-moderate pemphigus vulgaris or foliaceus were enrolled in an open-label phase II adaptive trial. In sequential cohorts, efgartigimod was dosed at 10 or 25 mg kg\(^{-1}\) intravenously with various dosing frequencies, as monotherapy or as add-on therapy to low-dose oral prednisone. Safety endpoints comprised the primary outcome. The study is registered at ClinicalTrials.gov (identifier NCT03334058).

Results
Adverse events were mostly mild and were reported by 16 of 19 (84%) patients receiving efgartigimod 10 mg kg\(^{-1}\) and 13 of 15 (87%) patients receiving 25 mg kg−1, with similar adverse event profiles between dose groups. A major decrease in serum total IgG and anti-desmoglein autoantibodies was observed and correlated with improved Pemphigus Disease Area Index scores. Efgartigimod, as monotherapy or combined with prednisone, demonstrated early disease control in 28 of 31 (90%) patients after a median of 17 days. Optimized, prolonged treatment with efgartigimod in combination with a median dose of prednisone 0·26 mg \(^{-1}\) per day (range 0·06–0·48) led to complete clinical remission in 14 of 22 (64%) patients within 2–41 weeks.

Conclusions
Efgartigimod was well tolerated and exhibited an early effect on disease activity and outcome parameters, providing support for further evaluation as a therapy for pemphigus.
KW  - pemphigus vulgaris
KW  - efgartigimod
KW  - pemphigus foliaceus
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258328
VL  - 186
IS  - 3
ER  - 
TY  - JOUR
A1  - Schmidt, Enno
A1  - Sticherling, Michael
A1  - Sárdy, Miklós
A1  - Eming, Rüdiger
A1  - Goebeler, Matthias
A1  - Hertl, Michael
A1  - Hofmann, Silke C.
A1  - Hunzelmann, Nicolas
A1  - Kern, Johannes S.
A1  - Kramer, Harald
A1  - Nast, Alexander
A1  - Orzechowski, Hans‐Dieter
A1  - Pfeiffer, Christiane
A1  - Schuster, Volker
A1  - Sitaru, Cassian
A1  - Zidane, Miriam
A1  - Zillikens, Detlef
A1  - Worm, Margitta
T1  - S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid: 2019 update
JF  - JDDG: Journal der Deutschen Dermatologischen Gesellschaft
KW  - pemphigus vulgaris
KW  - pemphigus foliaceus
KW  - S2k guidelines
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217806
VL  - 18
IS  - 5
SP  - 516
EP  - 526
ER  - 
TY  - JOUR
A1  - Hartlieb, Eva
A1  - Kempf, Bettina
A1  - Partilla, Miriam
A1  - Vigh, Balázs
A1  - Spindler, Volker
A1  - Waschke, Jens
T1  - Desmoglein 2 Is Less Important than Desmoglein 3 for Keratinocyte Cohesion
JF  - PLoS ONE
N2  - Desmosomes provide intercellular adhesive strength required for integrity of epithelial and some non-epithelial tissues. Within the epidermis, the cadherin-type adhesion molecules desmoglein (Dsg) 1-4 and desmocollin (Dsc) 1-3 build the adhesive core of desmosomes. In keratinocytes, several isoforms of these proteins are co-expressed. However, the contribution of specific isoforms to overall cell cohesion is unclear. Therefore, in this study we investigated the roles of Dsg2 and Dsg3, the latter of which is known to be essential for keratinocyte adhesion based on its autoantibody-induced loss of function in the autoimmune blistering skin disease pemphigus vulgaris (PV). The pathogenic PV antibody AK23, targeting the Dsg3 adhesive domain, led to profound loss of cell cohesion in human keratinocytes as revealed by the dispase-based dissociation assays. In contrast, an antibody against Dsg2 had no effect on cell cohesion although the Dsg2 antibody was demonstrated to interfere with Dsg2 transinteraction by single molecule atomic force microscopy and was effective to reduce cell cohesion in intestinal epithelial Caco-2 cells which express Dsg2 as the only Dsg isoform. To substantiate these findings, siRNA-mediated silencing of Dsg2 or Dsg3 was performed in keratinocytes. In contrast to Dsg3-depleted cells, Dsg2 knockdown reduced cell cohesion only under conditions of increased shear. These experiments indicate that specific desmosomal cadherins contribute differently to keratinocyte cohesion and that Dsg2 compared to Dsg3 is less important in this context.
KW  - expression
KW  - inhibition
KW  - DSG2
KW  - cell adhesion
KW  - desmosomal cadherins
KW  - pemphigus vulgaris
KW  - phenotype
KW  - mice
KW  - transinteraction
KW  - reorganization
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131192
VL  - 8
IS  - 1
ER  -