Abstract: P604
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Since the 2012 identification of 3 risk factors for natalizumab-associated progressive multifocal leucoencephalopathy (PML)presence of anti-JC virus (JCV) antibodies, prior immunosuppressant (IS) use, and longer treatment durationchanges in the PML incidence rate have been of interest.
Objective: Determine the natalizumab-associated PML incidence over time in the global postmarketing setting since introduction of the anti-JCV antibody assay and evaluate the relationship of PML incidence with natalizumab exposure over time.
Methods: The incidence of confirmed PML cases in Biogen's global safety database from November 2009 to November 2017 was evaluated retrospectively. Overall incidence in all exposed patients was determined by the estimated total number of patients ever exposed to natalizumab and the number of confirmed PML cases. Changes in natalizumab exposure patterns over time were evaluated by 12-infusion epochs. As individual-level data for anti-JCV antibody status and history of prior IS use are often not available in the postmarketing setting, this evaluation focused on overall PML incidence and exposure (based on postmarketing data).
Results: As of 30 November 2017, 180,656 patients worldwide had received ≥1 natalizumab dose (total exposure: 625,451 patient-years); overall natalizumab-associated PML incidence was 4.19/1000 patients. The increase in overall monthly incidence reported from 2012 onward appears to level off in mid-2016; overall incidence remained between 4.18-4.24/1000 over the last 21 months. PML incidence was greatest in the later, higher risk infusion epochs (37-48, 49-60, and 61-72); however, the number of patients in these higher risk epochs increased over time, with the most dramatic percentage increase between 2011 and 2013. This may have been a key factor in the increased overall PML incidence during that period. Increases in the proportion of patients in later exposure epochs (>24 infusions) declined from 2013-2015 and further from 2015-2017, coinciding with a slower increase in overall PML incidence from 2013 onward and the flattening observed since mid-2016.
Conclusions: Overall PML incidence has been stable since mid-2016. This stabilisation coincides with the introduction and publication of a new risk algorithm, suggesting that risk stratification factors are being incorporated into clinical practice and may continue to impact future PML incidence.
Disclosure: Supported by Biogen.
GG: served on steering committees for AbbVie, Atara, Biogen, Novartis, Roche, Teva; consultancy fees from Biogen, Canbex, GlaxoSmithKline, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Synthon.
LK: Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, Sanofi-Aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
JB: research support from Biogen; fees for consultancy from Abbvie, Astra-Zeneca, Alkermes, Biogen, Genentech/Roche, Novartis, Takeda/Millennium, Inhibikase, Excision Bio.
GC: served on data and safety monitoring boards for AMO Pharmaceuticals, Apotek, Horizon Pharmaceuticals, Merck, Merck/Pfizer, Modigenetech/Prolor, Neurim, Opko Biologics, Reata, Receptos/Celgene, Sanofi, Teva, NHLBI (Protocol Review Committee), NICHD (OPRU oversight committee); received compensation for consulting or advisory boards from Argenix, Atara Biotherapeutics, Bioeq GmBH, Consortium of MS Centers (grant), Genentech, Genzyme, Innate Therapeutics, Klein-Buendel, MedDay, MedImmune, Novartis, Opexa, Roche, Savara, Somahlution, Teva, TG Therapeutics, Transparency Life Sciences; and is president of Pythagoras, a private consulting company.
RF: consulting fees from Actelion, Biogen, Genentech, Mallinckrodt, MedDay, Novartis, Teva, XenoPort; advisory board fees from Biogen, Novartis; grant/research support from Novartis.
HW: honoraria from AbbVie, Actelion, Alexion, Biogen, Cognomed, Evgen, Hoffmann-La Roche, MedDay, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva; research support from Biogen, GlaxoSmithKline GmbH, Roche, Sanofi-Genzyme.
IC, RK, LL, SL, PRH: employees of and may hold stock and/or stock options in Biogen.
Abstract: P604
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Since the 2012 identification of 3 risk factors for natalizumab-associated progressive multifocal leucoencephalopathy (PML)presence of anti-JC virus (JCV) antibodies, prior immunosuppressant (IS) use, and longer treatment durationchanges in the PML incidence rate have been of interest.
Objective: Determine the natalizumab-associated PML incidence over time in the global postmarketing setting since introduction of the anti-JCV antibody assay and evaluate the relationship of PML incidence with natalizumab exposure over time.
Methods: The incidence of confirmed PML cases in Biogen's global safety database from November 2009 to November 2017 was evaluated retrospectively. Overall incidence in all exposed patients was determined by the estimated total number of patients ever exposed to natalizumab and the number of confirmed PML cases. Changes in natalizumab exposure patterns over time were evaluated by 12-infusion epochs. As individual-level data for anti-JCV antibody status and history of prior IS use are often not available in the postmarketing setting, this evaluation focused on overall PML incidence and exposure (based on postmarketing data).
Results: As of 30 November 2017, 180,656 patients worldwide had received ≥1 natalizumab dose (total exposure: 625,451 patient-years); overall natalizumab-associated PML incidence was 4.19/1000 patients. The increase in overall monthly incidence reported from 2012 onward appears to level off in mid-2016; overall incidence remained between 4.18-4.24/1000 over the last 21 months. PML incidence was greatest in the later, higher risk infusion epochs (37-48, 49-60, and 61-72); however, the number of patients in these higher risk epochs increased over time, with the most dramatic percentage increase between 2011 and 2013. This may have been a key factor in the increased overall PML incidence during that period. Increases in the proportion of patients in later exposure epochs (>24 infusions) declined from 2013-2015 and further from 2015-2017, coinciding with a slower increase in overall PML incidence from 2013 onward and the flattening observed since mid-2016.
Conclusions: Overall PML incidence has been stable since mid-2016. This stabilisation coincides with the introduction and publication of a new risk algorithm, suggesting that risk stratification factors are being incorporated into clinical practice and may continue to impact future PML incidence.
Disclosure: Supported by Biogen.
GG: served on steering committees for AbbVie, Atara, Biogen, Novartis, Roche, Teva; consultancy fees from Biogen, Canbex, GlaxoSmithKline, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Synthon.
LK: Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, Sanofi-Aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
JB: research support from Biogen; fees for consultancy from Abbvie, Astra-Zeneca, Alkermes, Biogen, Genentech/Roche, Novartis, Takeda/Millennium, Inhibikase, Excision Bio.
GC: served on data and safety monitoring boards for AMO Pharmaceuticals, Apotek, Horizon Pharmaceuticals, Merck, Merck/Pfizer, Modigenetech/Prolor, Neurim, Opko Biologics, Reata, Receptos/Celgene, Sanofi, Teva, NHLBI (Protocol Review Committee), NICHD (OPRU oversight committee); received compensation for consulting or advisory boards from Argenix, Atara Biotherapeutics, Bioeq GmBH, Consortium of MS Centers (grant), Genentech, Genzyme, Innate Therapeutics, Klein-Buendel, MedDay, MedImmune, Novartis, Opexa, Roche, Savara, Somahlution, Teva, TG Therapeutics, Transparency Life Sciences; and is president of Pythagoras, a private consulting company.
RF: consulting fees from Actelion, Biogen, Genentech, Mallinckrodt, MedDay, Novartis, Teva, XenoPort; advisory board fees from Biogen, Novartis; grant/research support from Novartis.
HW: honoraria from AbbVie, Actelion, Alexion, Biogen, Cognomed, Evgen, Hoffmann-La Roche, MedDay, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva; research support from Biogen, GlaxoSmithKline GmbH, Roche, Sanofi-Genzyme.
IC, RK, LL, SL, PRH: employees of and may hold stock and/or stock options in Biogen.