Contributions
Abstract: P1746
Type: Poster Sessions
Abstract Category: N/A
Background: Progressive multifocal leukoencephalopathy (PML) is the major limitation to the use of natalizumab in patients with multiple sclerosis (MS). Since 2012, three factors allow to identify patients in whom the risk of PML might overweight treatment benefits: exposure to natalizumab for more than 24 months, previous use of immunosuppressants and most of all a positive JC virus serology. So far, the impact of risk stratification on PML incidence has not been evaluated. Our main objective was to describe the temporal evolution of PML incidence in France.
Methods: Observational, multicentric, retrospective cohort in the setting of the Observatoire Français de la Sclérose en Plaques (OFSEP). Inclusion criteria: definite MS, at least one infusion of natalizumab between April 2007 and December 2016. Natalizumab-associated PML cases were identified in the database. Each participating center confirmed the diagnosis certainty, date of PML onset, association with natalizumab treatment, and whether the patient was originally followed in the center or referred because of the occurrence of PML. The later were excluded from the analyses. Incidence rates were defined as the number of PML cases reported to the number of person-years exposed to natalizumab. A Poisson regression model has been estimated for the whole 2007-2016 period to estimate the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation, and stratified by period (2007-2013, 2013-2016) to evaluate the impact of risk stratification.
Findings: 6318 patients were exposed to natalizumab during the study period, corresponding to 22414 person-years. 45 cases of confirmed PML were diagnosed in the same period. The crude incidence rate for the whole 2007-2016 period was 2.00 per 1000 exposed patients (95% confidence interval (CI) 1.46-2.69). The Poisson regression model showed a significant increase by 45.3% (IRR=1.453; 95% CI 1.154-1.828) each year in the incidence rate during the 2007-2013 period (p=0.001) and a significant decrease by 23.0% by year (IRR=0.770; 95% CI 0.609-0.973) since 2013 (p< 0.001).
Interpretation: Our result confirmed for the first time that risk stratification led to a decrease in natalizumab-related PML incidence since 2013 in France.
Funding: Agence Nationale de la Recherche ANR-10-COHO-002, Eugène Devic EDMUS Foundation against multiple sclerosis, ARSEP Foundation.
Disclosure: Sandra Vukusic has received consulting and lecturing fees, travel grants and unconditional research support from Biogen, Geneuro, Genzyme, MedDay, Merck Serono, Novartis, Roche, Sanofi Aventis and Teva Pharma.
Fabien Rollot has nothing to disclose.
Julie Pique has nothing to disclose.
Romain Casey has nothing to disclose.
Guillaume Mathey has nothing to disclose.
Gilles Edan has nothing to disclose.
David Brassat has nothing to disclose.
Aurélie Ruet has received consultancy fees, speaker fees, research grants (non personal), or honoraria approved by the institutions from Novartis, Biogen Idec, Genzyme, Medday, Roche, Teva and Merck, outside of the scope of the submitted study.
Jérôme De Sèze has nothing to disclose.
Hélène Zéphir received fees for consulting or lectures, and invitations for national and international congresses from Biogen, Merck, Teva, Sanofi-Genzyme, Novartis and Bayer, as well as research support from Teva and Roche, and academic research grants from Académie de Médecine, LFSEP, FHU Imminent and ARSEP Foundation.
Elisabeth Maillart received consulting and lecturing fees from Biogen, Novartis, Genzyme, Teva Pharmaceuticals, Merck Serono, Roche and Ad Scientiam and research support from Novartis and Roche.
Christine Lebrun-Frenay received fees for consulting or lectures from Biogen, Merck, Medday, Roche and Novartis.
Nathalie Derache has received funding for speakers honoraria from Merck-Serono, Biogen-Idec, Sanofi-Genzyme, Novartis and Roche.
Pierre Labauge has nothing to disclose.
Thibault Moreau has nothing to disclose.
David Laplaud has received consulting and lecturing fees, travel grants and unconditional research support from Biogen, Genzyme, Novartis, Merck Serono, Roche, Sanofi Aventis and Teva Pharma.
Eric Berger has nothing to disclose.
Xavier Moisset has received funding from Teva, Novartis, Sanofi-Genzyme, Merck-Serono, and Astellas, and non-financial support from Biogen, Sanofi-Pasteur-MSD, GSK, Astrazeneca, Pfizer, and Roche, not related to the submitted work
Audrey Rico-Lamy has nothing to disclose.
Eric Thouvenot has nothing to disclose.
Bruno Stankoff has received consulting and lecturing fees, travel grants and unconditional research support from Biogen Idec, Merck-Serono, Novartis, Genzyme, Teva Pharma, and Roche; has a patent pending for the identification of a compound that stimulates demyelination; and received academic research support from ANR, PHRC, ARSEP Foundation and the Progressive MS Alliance.
Olivier Heinzlef received consulting and lecturing fees from Bayer Schering, Merck, Teva, Genzyme, Novartis, Almirall and BiogenIdec, travel grants from Novartis, Teva, Genzyme, Merck Serono and Biogen Idec and research support from Roche, Merck and Novartis.
Bertrand Bourre served on scientific advisory board for Merck Serono and has received funding for travel and honoraria from Biogen, Merck Serono, Novartis, Sanofi-Genzyme, Roche and Teva.
Abdullatif Al-Kedhr has nothing to disclose.
Caroline Bensa has received consulting and lecturing fees, travel grants from Biogen, Genzyme, Novartis, Merck Serono, Roche and Teva Pharma.
Philippe Cabre has nothing to disclose.
Alexis Montcuquet has received funding for travel from Merck Serono, Teva, Novartis, Sanofi-Genzyme and Biogen.
Mathieu Vaillant has nothing to disclose.
Jean-Philippe Camdessanché has nothing to disclose.
Anne-Marie Guennoc received fees for consulting or lectures from Biogen, Merck, Sanofi-Genzyme and Roche.
Abir Wahab has nothing to disclose.
Nicolas Maubeuge has nothing to disclose.
Céline Labeyrie received consulting and lecturing fees from Biogen, Novartis and Genzyme.
Ivania Patry has received honoraria and consulting fees from Novartis, Genzyme and Roche, research supports from Biogen and Novartis and travel grants from Genzyme, Novartis and Roche.
Chantal Nifle has nothing to disclose.
Karolina Hankiewicz has nothing to disclose.
Abstract: P1746
Type: Poster Sessions
Abstract Category: N/A
Background: Progressive multifocal leukoencephalopathy (PML) is the major limitation to the use of natalizumab in patients with multiple sclerosis (MS). Since 2012, three factors allow to identify patients in whom the risk of PML might overweight treatment benefits: exposure to natalizumab for more than 24 months, previous use of immunosuppressants and most of all a positive JC virus serology. So far, the impact of risk stratification on PML incidence has not been evaluated. Our main objective was to describe the temporal evolution of PML incidence in France.
Methods: Observational, multicentric, retrospective cohort in the setting of the Observatoire Français de la Sclérose en Plaques (OFSEP). Inclusion criteria: definite MS, at least one infusion of natalizumab between April 2007 and December 2016. Natalizumab-associated PML cases were identified in the database. Each participating center confirmed the diagnosis certainty, date of PML onset, association with natalizumab treatment, and whether the patient was originally followed in the center or referred because of the occurrence of PML. The later were excluded from the analyses. Incidence rates were defined as the number of PML cases reported to the number of person-years exposed to natalizumab. A Poisson regression model has been estimated for the whole 2007-2016 period to estimate the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation, and stratified by period (2007-2013, 2013-2016) to evaluate the impact of risk stratification.
Findings: 6318 patients were exposed to natalizumab during the study period, corresponding to 22414 person-years. 45 cases of confirmed PML were diagnosed in the same period. The crude incidence rate for the whole 2007-2016 period was 2.00 per 1000 exposed patients (95% confidence interval (CI) 1.46-2.69). The Poisson regression model showed a significant increase by 45.3% (IRR=1.453; 95% CI 1.154-1.828) each year in the incidence rate during the 2007-2013 period (p=0.001) and a significant decrease by 23.0% by year (IRR=0.770; 95% CI 0.609-0.973) since 2013 (p< 0.001).
Interpretation: Our result confirmed for the first time that risk stratification led to a decrease in natalizumab-related PML incidence since 2013 in France.
Funding: Agence Nationale de la Recherche ANR-10-COHO-002, Eugène Devic EDMUS Foundation against multiple sclerosis, ARSEP Foundation.
Disclosure: Sandra Vukusic has received consulting and lecturing fees, travel grants and unconditional research support from Biogen, Geneuro, Genzyme, MedDay, Merck Serono, Novartis, Roche, Sanofi Aventis and Teva Pharma.
Fabien Rollot has nothing to disclose.
Julie Pique has nothing to disclose.
Romain Casey has nothing to disclose.
Guillaume Mathey has nothing to disclose.
Gilles Edan has nothing to disclose.
David Brassat has nothing to disclose.
Aurélie Ruet has received consultancy fees, speaker fees, research grants (non personal), or honoraria approved by the institutions from Novartis, Biogen Idec, Genzyme, Medday, Roche, Teva and Merck, outside of the scope of the submitted study.
Jérôme De Sèze has nothing to disclose.
Hélène Zéphir received fees for consulting or lectures, and invitations for national and international congresses from Biogen, Merck, Teva, Sanofi-Genzyme, Novartis and Bayer, as well as research support from Teva and Roche, and academic research grants from Académie de Médecine, LFSEP, FHU Imminent and ARSEP Foundation.
Elisabeth Maillart received consulting and lecturing fees from Biogen, Novartis, Genzyme, Teva Pharmaceuticals, Merck Serono, Roche and Ad Scientiam and research support from Novartis and Roche.
Christine Lebrun-Frenay received fees for consulting or lectures from Biogen, Merck, Medday, Roche and Novartis.
Nathalie Derache has received funding for speakers honoraria from Merck-Serono, Biogen-Idec, Sanofi-Genzyme, Novartis and Roche.
Pierre Labauge has nothing to disclose.
Thibault Moreau has nothing to disclose.
David Laplaud has received consulting and lecturing fees, travel grants and unconditional research support from Biogen, Genzyme, Novartis, Merck Serono, Roche, Sanofi Aventis and Teva Pharma.
Eric Berger has nothing to disclose.
Xavier Moisset has received funding from Teva, Novartis, Sanofi-Genzyme, Merck-Serono, and Astellas, and non-financial support from Biogen, Sanofi-Pasteur-MSD, GSK, Astrazeneca, Pfizer, and Roche, not related to the submitted work
Audrey Rico-Lamy has nothing to disclose.
Eric Thouvenot has nothing to disclose.
Bruno Stankoff has received consulting and lecturing fees, travel grants and unconditional research support from Biogen Idec, Merck-Serono, Novartis, Genzyme, Teva Pharma, and Roche; has a patent pending for the identification of a compound that stimulates demyelination; and received academic research support from ANR, PHRC, ARSEP Foundation and the Progressive MS Alliance.
Olivier Heinzlef received consulting and lecturing fees from Bayer Schering, Merck, Teva, Genzyme, Novartis, Almirall and BiogenIdec, travel grants from Novartis, Teva, Genzyme, Merck Serono and Biogen Idec and research support from Roche, Merck and Novartis.
Bertrand Bourre served on scientific advisory board for Merck Serono and has received funding for travel and honoraria from Biogen, Merck Serono, Novartis, Sanofi-Genzyme, Roche and Teva.
Abdullatif Al-Kedhr has nothing to disclose.
Caroline Bensa has received consulting and lecturing fees, travel grants from Biogen, Genzyme, Novartis, Merck Serono, Roche and Teva Pharma.
Philippe Cabre has nothing to disclose.
Alexis Montcuquet has received funding for travel from Merck Serono, Teva, Novartis, Sanofi-Genzyme and Biogen.
Mathieu Vaillant has nothing to disclose.
Jean-Philippe Camdessanché has nothing to disclose.
Anne-Marie Guennoc received fees for consulting or lectures from Biogen, Merck, Sanofi-Genzyme and Roche.
Abir Wahab has nothing to disclose.
Nicolas Maubeuge has nothing to disclose.
Céline Labeyrie received consulting and lecturing fees from Biogen, Novartis and Genzyme.
Ivania Patry has received honoraria and consulting fees from Novartis, Genzyme and Roche, research supports from Biogen and Novartis and travel grants from Genzyme, Novartis and Roche.
Chantal Nifle has nothing to disclose.
Karolina Hankiewicz has nothing to disclose.