Lidia Stork1, Wolfgang Brück1, Phillip von Gottberg2, Ulrich Pulkowski3, Florian Kirsten3, Markus Glatzel4, Sebastian Rauer5, Franziska Scheibe6, Helena Radbruch7, Eckhard Hammer8, Klarissa H Stürner9, Barbara Kaulen10, Christoph Heesen10, Frank Hoffmann11, Sebastian Brock11, Marc Pawlitzki12, Tobias Bopp13, Imke Metz1. 1. Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany. 2. Institute of Neuroradiology, University Medical Center Göttingen, Göttingen, Germany. 3. Department of Neurology, Imland Hospital, Rendsburg, Germany. 4. Institute of Neuropathology, University Hospital Hamburg Eppendorf, Hamburg, Germany. 5. Department of Neurology, University Medical Center Freiburg, Freiburg, Germany. 6. Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany. 7. Institute of Neuropathology, Charité-Universitätsmedizin Berlin, Berlin, Germany. 8. Department of Neurology, Marienkrankenhaus, Hamburg, Germany. 9. Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany. 10. Department of Neurology, University Hospital Hamburg Eppendorf, Hamburg, Germany; Institute of Neuroimmunology and Multiple Sclerosis, University Hospital Hamburg Eppendorf, Hamburg, Germany. 11. Department of Neurology, Martha-Maria Hospital, Halle, Germany. 12. Department of Neurology, University Medical Center, Otto von Guericke University, Magdeburg, Germany. 13. Institute for Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Abstract
BACKGROUND: Daclizumab is a monoclonal antibody that binds the high-affinity interleukin-2 receptor and was approved for the treatment of relapsing multiple sclerosis. Due to severe inflammatory brain disorders, the approval was suspended in March 2018. OBJECTIVE AND METHODS: This retrospective cohort study summarizes clinical, laboratory, radiological, and histological findings of seven patients who developed meningo-/encephalitis after daclizumab therapy. RESULTS: Patients presented with encephalitis and/or meningitis and suffered from systemic symptoms such as fever (5/7), exanthema (5/7), or gastrointestinal symptoms (4/7). Secondary autoimmune diseases developed. Blood analysis revealed an increase in eosinophils (5/7). Six patients fulfilled the diagnostic criteria for a drug reaction with eosinophilia and systemic symptoms (DRESS). Magnetic resonance imaging (MRI) showed multiple contrast-enhancing lesions, and enhancement of the ependyma (6/7), meninges (5/7), cranial or spinal nerves (2/7), and a vasculitic pattern (3/7). Histology revealed a pronounced inflammatory infiltrate consisting of lymphocytes, plasma cells and eosinophils, and densely infiltrated vessels. Most patients showed an insufficient therapeutic response and a high disability at last follow-up (median Expanded Disability Status Scale (EDSS) 8). Two patients died. CONCLUSION: Meningoencephalitis and DRESS may occur with daclizumab therapy. This potential lethal side effect is characterized by a dysregulated immune response. Our findings underline the importance of postmarketing drug surveillance.
BACKGROUND:Daclizumab is a monoclonal antibody that binds the high-affinity interleukin-2 receptor and was approved for the treatment of relapsing multiple sclerosis. Due to severe inflammatory brain disorders, the approval was suspended in March 2018. OBJECTIVE AND METHODS: This retrospective cohort study summarizes clinical, laboratory, radiological, and histological findings of seven patients who developed meningo-/encephalitis after daclizumab therapy. RESULTS:Patients presented with encephalitis and/or meningitis and suffered from systemic symptoms such as fever (5/7), exanthema (5/7), or gastrointestinal symptoms (4/7). Secondary autoimmune diseases developed. Blood analysis revealed an increase in eosinophils (5/7). Six patients fulfilled the diagnostic criteria for a drug reaction with eosinophilia and systemic symptoms (DRESS). Magnetic resonance imaging (MRI) showed multiple contrast-enhancing lesions, and enhancement of the ependyma (6/7), meninges (5/7), cranial or spinal nerves (2/7), and a vasculitic pattern (3/7). Histology revealed a pronounced inflammatory infiltrate consisting of lymphocytes, plasma cells and eosinophils, and densely infiltrated vessels. Most patients showed an insufficient therapeutic response and a high disability at last follow-up (median Expanded Disability Status Scale (EDSS) 8). Two patientsdied. CONCLUSION:Meningoencephalitis and DRESS may occur with daclizumab therapy. This potential lethal side effect is characterized by a dysregulated immune response. Our findings underline the importance of postmarketing drug surveillance.
Authors: Ralf Gold; Ernst-Wilhelm Radue; Gavin Giovannoni; Krzysztof Selmaj; Eva Kubala Havrdova; Xavier Montalban; Dusan Stefoski; Till Sprenger; Randy R Robinson; Sami Fam; Jonathan Smith; Spyros Chalkias; Giorgio Giannattasio; Gabriel Lima; Wanda Castro-Borrero Journal: J Neurol Date: 2020-05-25 Impact factor: 4.849