N Venhoff1, F Proft2, H Schulze-Koops2, J Holle3,4, R E Voll1, C Iking-Konert5, A M Jacobi6, J Henes7, L Unger8, O Kneitz9, T Dörner10, J Thiel11. 1. Vaskulitiszentrum Freiburg, Klinik für Rheumatologie und Klinische Immunologie, Department Innere Medizin, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Hugstetterstraße 55, 79106, Freiburg, Deutschland. 2. Sektion Rheumatologie und Klinische Immunologie, Medizinische Klinik IV, Klinikum der Universität München, München, Deutschland. 3. Klinik für Rheumatologie und Immunologie, Klinikum Bad Bramstedt, Bad Bramstedt, Deutschland. 4. Rheumazentrum Schleswig-Holstein Mitte, Kuhberg 5 a-7, 24534, Neumünster, Deutschland. 5. Klinik für Nephrologie und Rheumatologie, Med. Klinik III, Universitätsklinik Hamburg Eppendorf (UKE), Martinistr. 52, 20246, Hamburg, Deutschland. 6. Medizinische Klinik B, Ruppiner Kliniken, Medizinische Hochschule Brandenburg Theodor Fontane, Neuruppin, Deutschland. 7. Abteilung für Onkologie, Hämatologie, klinische Immunologie, Rheumatologie, Pulmologie, Medizinische Klinik, Universität Tübingen, Tübingen, Deutschland. 8. Department Medizin I, Dresden Friedrichstadt Hospital, University Clinical Center Carl Gustav Carus, Schwerpunktpraxis Rheumatologie, Technische Universität Dresden, Dresden, Deutschland. 9. Klinik für Innere Medizin II, Rheumatologie und klinische Immunologie, Klinikum Südstadt Rostock, Rostock, Deutschland. 10. Medizinische Klinik m. S. Rheumatologie und klinische Immunologie, Charité Universitätsmedizin Berlin und DRFZ Berlin, Berlin, Deutschland. 11. Vaskulitiszentrum Freiburg, Klinik für Rheumatologie und Klinische Immunologie, Department Innere Medizin, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Hugstetterstraße 55, 79106, Freiburg, Deutschland. jens.thiel@uniklinik-freiburg.de.
Abstract
OBJECTIVE: To evaluate the clinical efficacy and safety of off-label biological therapies in patients with ANCA-associated vasculitis (AAV) and non-ANCA-associated small-vessel vasculitis (nAAV) in clinical practice. METHODS: The German Registry in Autoimmune Diseases 2 (GRAID2) is a national, retrospective, non-interventional, multicentre observational study (August 2006 until December 2013) on patients with autoimmune diseases refractory to standard immunosuppressive therapy treated with off-label biologicals. RESULTS: Data from 64 patients (20.6% of all GRAID2 patients) were collected: 54 patients (84.4%) had ANCA-associated vasculitis (AAV) and 10 patients (15.6%) had non-ANCA-associated small-vessel vasculitis (nAAV). Of the AAV patients, 96.3% were treated off-label with rituximab (RTX) and 3.7% with tumor necrosis factor alpha (TNFα)-inhibitors. Of patients with nAAV, 30% were treated with RTX, 60% with TNFα-inhibitors, and 10% with tocilizumab. The main reasons for off-label biological treatment in AAV patients were pulmonary, renal, or ear, nose, and throat involvement. These manifestations clearly improved in most patients after off-label biological therapy was initiated. Daily glucocorticoid dosage could be reduced. The off-label biological therapy was generally well tolerated. In AAV patients, 4.18 severe infections per 100 patient years were observed. There was one death in the nAAV group caused by fungal infection and ileus. A correlation between this fatality and RTX treatment was regarded as possible. CONCLUSION: Safety and efficacy of off-label RTX-treatment in AAV-patients could be assessed in the GRAID2 data. Results point to good efficacy and safety of RTX in this special patient cohort and support the approval of RTX for AAV induction therapy.
OBJECTIVE: To evaluate the clinical efficacy and safety of off-label biological therapies in patients with ANCA-associated vasculitis (AAV) and non-ANCA-associated small-vessel vasculitis (nAAV) in clinical practice. METHODS: The German Registry in Autoimmune Diseases 2 (GRAID2) is a national, retrospective, non-interventional, multicentre observational study (August 2006 until December 2013) on patients with autoimmune diseases refractory to standard immunosuppressive therapy treated with off-label biologicals. RESULTS: Data from 64 patients (20.6% of all GRAID2 patients) were collected: 54 patients (84.4%) had ANCA-associated vasculitis (AAV) and 10 patients (15.6%) had non-ANCA-associated small-vessel vasculitis (nAAV). Of the AAV patients, 96.3% were treated off-label with rituximab (RTX) and 3.7% with tumor necrosis factor alpha (TNFα)-inhibitors. Of patients with nAAV, 30% were treated with RTX, 60% with TNFα-inhibitors, and 10% with tocilizumab. The main reasons for off-label biological treatment in AAV patients were pulmonary, renal, or ear, nose, and throat involvement. These manifestations clearly improved in most patients after off-label biological therapy was initiated. Daily glucocorticoid dosage could be reduced. The off-label biological therapy was generally well tolerated. In AAV patients, 4.18 severe infections per 100 patient years were observed. There was one death in the nAAV group caused by fungal infection and ileus. A correlation between this fatality and RTX treatment was regarded as possible. CONCLUSION: Safety and efficacy of off-label RTX-treatment in AAV-patients could be assessed in the GRAID2 data. Results point to good efficacy and safety of RTX in this special patient cohort and support the approval of RTX for AAV induction therapy.
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