BACKGROUND: In the clinical trials about 9% of natalizumab treated multiple sclerosis (MS) patients generated anti-natalizumab antibodies, of which 6% were persistent and 3% transient. The occurrence of antibodies reduced serum levels of natalizumab, decreased bio-efficacy, and abrogated the therapeutic efficacy. OBJECTIVE: The objective was to assess the frequency of anti-natalizumab antibodies in an unselected cohort of patients from four different countries. METHODS: We measured anti-natalizumab antibodies in a large cohort of 4881 unselected patients from four MS centres that systematically measured antibodies in patients treated with natalizumab. We applied the same ELISA assay developed by Biogen Idec and used in the pivotal trials of natalizumab. RESULTS: Antibodies occurred in 4.5% (95% confidence interval, CI: 4.0-5.1%) of the patients, and were persistent in 3.5% (95% CI: 3.0-4.0%) and transient in 1.0% (95% CI: 0.7-1.3%) of the patients. The frequencies of permanently antibody positive patients did not show statistically significant differences between the four centres, whereas the frequencies of transiently antibody positive patients showed some variations. CONCLUSION: The frequencies of antibodies appeared to be of the same magnitude in the four centres, but might be less than in the pivotal studies of natalizumab.
BACKGROUND: In the clinical trials about 9% of natalizumab treated multiple sclerosis (MS) patients generated anti-natalizumab antibodies, of which 6% were persistent and 3% transient. The occurrence of antibodies reduced serum levels of natalizumab, decreased bio-efficacy, and abrogated the therapeutic efficacy. OBJECTIVE: The objective was to assess the frequency of anti-natalizumab antibodies in an unselected cohort of patients from four different countries. METHODS: We measured anti-natalizumab antibodies in a large cohort of 4881 unselected patients from four MS centres that systematically measured antibodies in patients treated with natalizumab. We applied the same ELISA assay developed by Biogen Idec and used in the pivotal trials of natalizumab. RESULTS: Antibodies occurred in 4.5% (95% confidence interval, CI: 4.0-5.1%) of the patients, and were persistent in 3.5% (95% CI: 3.0-4.0%) and transient in 1.0% (95% CI: 0.7-1.3%) of the patients. The frequencies of permanently antibody positive patients did not show statistically significant differences between the four centres, whereas the frequencies of transiently antibody positive patients showed some variations. CONCLUSION: The frequencies of antibodies appeared to be of the same magnitude in the four centres, but might be less than in the pivotal studies of natalizumab.
Authors: Zoé L E van Kempen; Johannis A van Rossum; Djoeke Doesburg; Iris Claessen; Annick de Vries; Anja Ten Brinke; Bob W van Oosten; Theo Rispens; Joep Killestein Journal: J Neurol Date: 2019-04-19 Impact factor: 4.849
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Authors: Moritz Förster; Patrick Küry; Orhan Aktas; Clemens Warnke; Joachim Havla; Reinhard Hohlfeld; Jan Mares; Hans-Peter Hartung; David Kremer Journal: Drug Saf Date: 2019-05 Impact factor: 5.606
Authors: Andrea Harrer; Georg Pilz; Max Einhaeupl; Katrin Oppermann; Wolfgang Hitzl; Peter Wipfler; Johann Sellner; Stefan Golaszewski; Shahrzad Afazel; Elisabeth Haschke-Becher; Eugen Trinka; Joerg Kraus Journal: PLoS One Date: 2012-02-20 Impact factor: 3.240
Authors: Tjalf Ziemssen; Ovidiu A Bajenaru; Adriana Carrá; Nina de Klippel; João C de Sá; Astrid Edland; Jette L Frederiksen; Olivier Heinzlef; Klimentini E Karageorgiou; Rafael H Lander Delgado; Anne-Marie Landtblom; Miguel A Macías Islas; Niall Tubridy; Yossi Gilgun-Sherki Journal: J Neurol Date: 2014-08-14 Impact factor: 4.849