F Proft1,2, H Schulze-Koops3, M Grunke3, E Schrezenmeier4, F Halleck4, J Henes5, L Unger6, E Schmidt7, C Fiehn8, A Jacobi9, C Iking-Konert10, C Kneitz11, R E Schmidt12, B Bannert13, R E Voll13, R Fischer-Betz14, I Kötter5,15, H P Tony16, J Holle17,18, M Aringer19, A Erler19, F Behrens20, G R Burmester21, T Dörner21. 1. Sektion Rheumatologie und Klinische Immunologie, Medizinische Klinik IV, Klinikum der Universität München, München, Deutschland. Fabian.Proft@charite.de. 2. Abteilung für Rheumatologie, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Campus Benjamin Franklin, Charité Universitätsmedizin, Berlin, Deutschland. Fabian.Proft@charite.de. 3. Sektion Rheumatologie und Klinische Immunologie, Medizinische Klinik IV, Klinikum der Universität München, München, Deutschland. 4. Medizinische Klinik m.S. Nephrologie, Campus Mitte, Charité Universitätsmedizin, Berlin, Deutschland. 5. Abteilung für Onkologie, Hämatologie, klinische Immunologie, Rheumatologie, Pulmologie, Medizinische Klinik II, Universität Tübingen, Tübingen, Deutschland. 6. Abteilung für Rheumatologie, I. Medizinische Klinik, Städtisches Klinikum Dresden, Dresden, Deutschland. 7. Klinik für Dermatologie, Allergologie und Venerologie, Universität zu Lübeck, Lübeck, Deutschland. 8. Praxis für Rheumatologie und klinische Immunologie, Baden-Baden, Deutschland. 9. Medizinische Klinik B, Ruppiner Kliniken, Medizinische Hochschule Brandenburg Theodor Fontane, Neuruppin, Deutschland. 10. Klinik für Nephrologie und Rheumatologie, UKE-Hamburg-Eppendorf und Klinik für Rheumatologie und Immunologie, Klinikum Bad Bramstedt, Bad Bramstedt, Deutschland. 11. Klinik für Innere Medizin II, Rheumatologie und klinische Immunologie, Klinikum Suedstadt Rostock, Rostock, Deutschland. 12. Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Deutschland. 13. Klinik für Rheumatologie und Klinische Immunologie, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg, Deutschland. 14. Poliklinik für Rheumatologie & Hiller-Forschungszentrum, Universitätsklinikum, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Deutschland. 15. 4. Medizinische Abteilung, Rheumatologie, Klinische Immunologie, Nephrologie, Asklepios Klinik Altona, Hamburg, Deutschland. 16. Abteilung für Rheumatologie und klinische Immunologie, Zentrum für Innere Medizin, Universitätsklinikum Würzburg, Würzburg, Deutschland. 17. Klinik für Rheumatologie und Immunologie, Klinikum Bad Bramstedt, Bad Bramstedt, Deutschland. 18. Rheumazentrum Schleswig-Holstein Mitte, Neumünster, Deutschland. 19. Medizinische Klinik und Poliklinik III, Universitätsklinikum und Medizinische Fakultät Carl Gustav Carus an der TU Dresden, Dresden, Deutschland. 20. CIRI/Rheumatologie und Fraunhofer Institut IME, Translationale Medizin und Pharmakologie, Universitätsklinikum Goethe Universität Frankfurt am Main, Frankfurt am Main, Deutschland. 21. Medizinische Klinik m.S. Rheumatologie und Klinische Immunologie, Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Deutschland.
Abstract
BACKGROUND: The German Registry of Autoimmune Diseases 2 (GRAID2) is a retrospective, non-interventional, multicenter registry study collecting data from patients with inflammatory, mainly rheumatic diseases refractory to standard of care therapy and treated with an off-label biologic therapy. The retrospective documentation comprised case history, diagnosis, course of disease (including safety and global efficacy). The objective was to evaluate the global clinical outcome and safety of off-label biologic therapy in clinical practice. RESULTS: Data from 311 patients with an overall observation period of 338.5 patient-years were collected. The mean patients age was 47.8 years with 56.9% females. The most frequently documented diagnoses comprised rejection prophylaxis/therapy after renal transplantation (NTX, 18.3%), ANCA-vasculitides (17.4%), systemic lupus erythematosus (SLE, 10.3%), autoinflammatory fever syndromes (8.4%), autoimmune myositis (7.4%) and pemphigus (5.8%). Documented biologic therapies included rituximab (RTX, 70.1%), tocilizumab (TCZ, 9.3%), infliximab (IFX, 7.1%), anakinra (ANK, 5.5%), adalimumab (ADA, 3.5%), etanercept (ETA, 2.3%) and certolizumab (CTZ, 0.6%). After initiation of off-label biologic treatment, tolerability was assessed by the physicians as "very good"/"good" in 95.5%. Altogether, 275 adverse events were documented and of these, 104 were classified as serious adverse events and occurred in 62 patients. In 19 of these patients severe infections (30.6%) were documented, resulting in a rate of 5.6 severe infections per 100 patient years. A total of six deaths were documented, while five of these cases were rated as not related to the biologics treatment. Notably, the use of RTX in patients with small vessel vasculitides and of TCZ in patients with large vessel vasculitides prior to their approval support their relevance in clinical management of patients with severe diseases. CONCLUSION: The results of this registry together with data of GRAID1 provide evidence that use of off-label biologic therapies in patients with inflammatory rheumatic diseases refractory to conventional treatment did not result in any new safety signal already known for these compounds or subsequently shown by clinical trials in certain entities.
BACKGROUND: The German Registry of Autoimmune Diseases 2 (GRAID2) is a retrospective, non-interventional, multicenter registry study collecting data from patients with inflammatory, mainly rheumatic diseases refractory to standard of care therapy and treated with an off-label biologic therapy. The retrospective documentation comprised case history, diagnosis, course of disease (including safety and global efficacy). The objective was to evaluate the global clinical outcome and safety of off-label biologic therapy in clinical practice. RESULTS: Data from 311 patients with an overall observation period of 338.5 patient-years were collected. The mean patients age was 47.8 years with 56.9% females. The most frequently documented diagnoses comprised rejection prophylaxis/therapy after renal transplantation (NTX, 18.3%), ANCA-vasculitides (17.4%), systemic lupus erythematosus (SLE, 10.3%), autoinflammatory fever syndromes (8.4%), autoimmune myositis (7.4%) and pemphigus (5.8%). Documented biologic therapies included rituximab (RTX, 70.1%), tocilizumab (TCZ, 9.3%), infliximab (IFX, 7.1%), anakinra (ANK, 5.5%), adalimumab (ADA, 3.5%), etanercept (ETA, 2.3%) and certolizumab (CTZ, 0.6%). After initiation of off-label biologic treatment, tolerability was assessed by the physicians as "very good"/"good" in 95.5%. Altogether, 275 adverse events were documented and of these, 104 were classified as serious adverse events and occurred in 62 patients. In 19 of these patients severe infections (30.6%) were documented, resulting in a rate of 5.6 severe infections per 100 patient years. A total of six deaths were documented, while five of these cases were rated as not related to the biologics treatment. Notably, the use of RTX in patients with small vessel vasculitides and of TCZ in patients with large vessel vasculitides prior to their approval support their relevance in clinical management of patients with severe diseases. CONCLUSION: The results of this registry together with data of GRAID1 provide evidence that use of off-label biologic therapies in patients with inflammatory rheumatic diseases refractory to conventional treatment did not result in any new safety signal already known for these compounds or subsequently shown by clinical trials in certain entities.
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