Year: 2026
Type: article
Abstract: Autoimmune-mediated connective tissue diseases such as antisynthetase syndrome (ASyS) and systemic sclerosis (SSc) have a high unmet medical need. Here we report on treatment under compassionate use with the CD19×CD3 T cell engager (TCE) blinatumomab and the BCMA×CD3 TCE teclistamab in five patients with treatment-refractory ASyS and in five patients with treatment-refractory SSc, respectively. Induction therapy with blinatumomab or teclistamab reduced target cells in affected muscle and skin, respectively, and decreased autoantibody titers. Blinatumomab induced rapid clinical, serological and histological improvement of myositis and stabilization of interstitial lung disease (ILD) in patients with ASyS. Teclistamab improved skin fibrosis, stabilized ILD and resolved tendon friction rubs in patients with SSc. Inhibition of B cell redifferentiation by maintenance therapy with rituximab (RTX) enabled prolonged disease control, even for patients previously unresponsive to RTX. Treatment was associated with adverse events including cytokine release syndrome (CRS) up to grade 3, in two patients with ASyS and in all patients with SSc. No immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. Respiratory infections treated with antibiotics occurred in six patients. Blinatumomab and teclistamab may offer potential as rescue therapies for patients with treatment-refractory ASyS and SSc.
Source: Nature Medicine
Authors: Christina Düsing, Andrea-Hermina Györfi, Ayla Nadja Stütz, Laura-Marie Lahu, Franca Sophie Deicher, Yi-Nan Li, Peter-Martin Bruch, Alexandru-Emil Matei, Alexandru Micu, Tim Filla, Sarah Koziel, Alexander Sebastian Hölscher, Manuel Röhrich, Hanns-Martin Lorenz, Mareike Cramer, Gerald Antoch, Jörg Timm, Yousef Abusabha, Tobias Ruck, Bernhard Homey, Alexander Kreuter, Björn Buehring, Aleksandar Radujkovic, Claus Peter Heußel, Melanie Hagen, Ricardo Grieshaber-Bouyer, Georg Schett, Anna Brunn, Sascha Dietrich, Wolfgang Merkt, Jörg H. W. Distler
Institutions: Düsseldorf University Hospital, Fraunhofer Institute for Translational Medicine and Pharmacology, Heinrich Heine University Düsseldorf, University Medical Center of the Johannes Gutenberg University Mainz, Heidelberg University, University Hospital Heidelberg, BG University Hospital Bergmannsheil Bochum, Ruhr University Bochum, HELIOS St. Elisabeth Klinik Oberhausen, German Center for Lung Research, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Awards: G101308371, G1037940132, G1056646705, G1741633616, G286874467, MASCARA - Molekulare Charakterisierung der Remission von Arthritis - Immunmetabolismus, mesenchymale Gewebeantwort, residente Immunzellen, Barrierefunktion des Darms, G3550260248, G378208582, G4045315607, G4501061758, TRR 221: Steuerung der TransplantatgegenWirt und TransplantatgegenLeukämieImmunreaktionen nach allogener Stammzelltransplantation, G749678917
OpenAlex ID: W7130511753