Contributions
Abstract: P689
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Natalizumab is a highly efficacious treatment for relapsing-remitting multiple sclerosis (RRMS). However, it fails to sufficiently prevent disease activity in some patients and is associated with an increased risk of progressive multifocal leukoencephalopathy (PML) that grows with treatment duration.
A significant proportion of patients therefore need to undergo a change in disease-modifying therapy (DMT). The currently available alternatives approved for (highly) active RRMS are alemtuzumab and fingolimod. However, so far there is no comparative data on the safety and efficacy of these substances after natalizumab cessation.
We therefore conducted a retrospective multicenter study of RRMS patients after cessation of natalizumab. 8 German centers provided data of about 130 patients who stopped natalizumab due to PML risk, or - in contrast to previous studies - required change of DMT due to breakthrough disease.
The primary outcome parameter was drug discontinuation rate after 12 months of treatment, whereas omission of a second infusion course defined treatment discontinuation for alemtuzumab. Furthermore, MRI data were included and adverse event profiles were analyzed for a follow-up period of 12 months.
Preliminary data indicate that alemtuzumab therapy is associated with fewer relapses, a reduced risk of disability progression and a lower likelihood of drug discontinuation. About 1 out of 10 patients discontinued treatment with alemtuzumab, whereas 1 out of 3 patients stopped fingolimod within the observation period, mostly because of breakthrough disease. Significant disability progression was detected in 1 out of 10 patients on alemtuzumab and in 1 out of 4 patients on fingolimod. Adverse events in the fingolimod group mainly comprised hepatopathy and lymphopenia. Alemtuzumab patients predominantly experienced infusion-associated reactions.
We conclude that alemtuzumab is a safe and efficacious alternative for patients that stopped natalizumab. It was superior to fingolimod in prevention of relapses and disability progression. Side effects were balanced between both groups; however, we did not yet discover secondary autoimmune disorders in the alemtuzumab group, which will expectedly peak in long-term follow-up. These data provide relevant advice for the development of treatment algorithms in patients with active RRMS. However, we are aware of the limitations of the retrospective study design.
This project is supported financially by Sanofi Genzyme
Disclosure:
Steffen Pfeuffer received travel reimbursements and lecturing honoraria from Sanofi Genzyme and Biogen.
Tobias Ruck received travel reimbursements and financial research support from Sanofi Genzyme and Novartis and lecturing honoraria from Sanofi Genzyme, Biogen and Teva.
Christoph Kleinschnitz and Marinus Wieshuber declare no conflicts of interest.
De-Hyung Lee received travel support and/or compensation for activities with Biogen, Genzyme, Merck, Novartis, Roche and TEVA as well as research support from Novartis.
Ralf Linker received travel support and/or compensation for activities with Allmirall, Bayer Healthcare, Biogen, Fresenius, Genzyme, Merck, Novartis, Roche and TEVA as well as research support from Biogen, Merck and Novartis.
Sebastian Doerck, Vera Straeten, Susanne Windhagen and Christoph Aufenberg declare no conflict of interest.
Michael Lang received travel reimbursements, lecturing honoraria, financial research support and consultancy fees from Teva, Merck Serono, Sanofi Genzyme, Novartis, Bayer and Biogen.
Christian Eienbröker declares no conflict of interest.
Björn Tackenberg received lecturing honoraria and consultancy fees as a speaker and advisor from Bayer Healthcare, Biogen, CSL Behring, GRIFOLS, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme, TEVA und UCB Pharma. His University received unrestricted research grants from Biogen-idec, Novartis, TEVA, Bayer Healthcare, CSL-Behring, GRIFOLS, Octapharma, Sanofi Genzyme und UCB Pharma.
Heinz Wiendl received compensation for serving on Scientific Advisory Boards/Steering Committees, for Bayer Healthcare, Biogen Idec, Sanofi Genzyme, Merck Serono and Novartis, lecturing honoraria and travel reimbursements from Bayer Vital, Bayer Schering, Biogen, CSL Behring, EMD Serono, Fresenius Medical Care, Sanofi Genzyme, Merck Serono, Omniamed, Novartis and Sanofi Aventis, compensation as a consultant from Biogen Idec, Merck Serono, Novartis, Roche and Sanofi Genzyme, financial research support from Bayer Healthcare, Bayer Vital, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, Sanofi US and TEVA Pharma.
Sven G. Meuth received lecturing honoraria, travel reimbursements and financial research support from Bayer, Bayer Schering, Biogen Idec, Sanofi Genzyme, Merck Serono, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi-Aventis and Teva.
Abstract: P689
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Natalizumab is a highly efficacious treatment for relapsing-remitting multiple sclerosis (RRMS). However, it fails to sufficiently prevent disease activity in some patients and is associated with an increased risk of progressive multifocal leukoencephalopathy (PML) that grows with treatment duration.
A significant proportion of patients therefore need to undergo a change in disease-modifying therapy (DMT). The currently available alternatives approved for (highly) active RRMS are alemtuzumab and fingolimod. However, so far there is no comparative data on the safety and efficacy of these substances after natalizumab cessation.
We therefore conducted a retrospective multicenter study of RRMS patients after cessation of natalizumab. 8 German centers provided data of about 130 patients who stopped natalizumab due to PML risk, or - in contrast to previous studies - required change of DMT due to breakthrough disease.
The primary outcome parameter was drug discontinuation rate after 12 months of treatment, whereas omission of a second infusion course defined treatment discontinuation for alemtuzumab. Furthermore, MRI data were included and adverse event profiles were analyzed for a follow-up period of 12 months.
Preliminary data indicate that alemtuzumab therapy is associated with fewer relapses, a reduced risk of disability progression and a lower likelihood of drug discontinuation. About 1 out of 10 patients discontinued treatment with alemtuzumab, whereas 1 out of 3 patients stopped fingolimod within the observation period, mostly because of breakthrough disease. Significant disability progression was detected in 1 out of 10 patients on alemtuzumab and in 1 out of 4 patients on fingolimod. Adverse events in the fingolimod group mainly comprised hepatopathy and lymphopenia. Alemtuzumab patients predominantly experienced infusion-associated reactions.
We conclude that alemtuzumab is a safe and efficacious alternative for patients that stopped natalizumab. It was superior to fingolimod in prevention of relapses and disability progression. Side effects were balanced between both groups; however, we did not yet discover secondary autoimmune disorders in the alemtuzumab group, which will expectedly peak in long-term follow-up. These data provide relevant advice for the development of treatment algorithms in patients with active RRMS. However, we are aware of the limitations of the retrospective study design.
This project is supported financially by Sanofi Genzyme
Disclosure:
Steffen Pfeuffer received travel reimbursements and lecturing honoraria from Sanofi Genzyme and Biogen.
Tobias Ruck received travel reimbursements and financial research support from Sanofi Genzyme and Novartis and lecturing honoraria from Sanofi Genzyme, Biogen and Teva.
Christoph Kleinschnitz and Marinus Wieshuber declare no conflicts of interest.
De-Hyung Lee received travel support and/or compensation for activities with Biogen, Genzyme, Merck, Novartis, Roche and TEVA as well as research support from Novartis.
Ralf Linker received travel support and/or compensation for activities with Allmirall, Bayer Healthcare, Biogen, Fresenius, Genzyme, Merck, Novartis, Roche and TEVA as well as research support from Biogen, Merck and Novartis.
Sebastian Doerck, Vera Straeten, Susanne Windhagen and Christoph Aufenberg declare no conflict of interest.
Michael Lang received travel reimbursements, lecturing honoraria, financial research support and consultancy fees from Teva, Merck Serono, Sanofi Genzyme, Novartis, Bayer and Biogen.
Christian Eienbröker declares no conflict of interest.
Björn Tackenberg received lecturing honoraria and consultancy fees as a speaker and advisor from Bayer Healthcare, Biogen, CSL Behring, GRIFOLS, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme, TEVA und UCB Pharma. His University received unrestricted research grants from Biogen-idec, Novartis, TEVA, Bayer Healthcare, CSL-Behring, GRIFOLS, Octapharma, Sanofi Genzyme und UCB Pharma.
Heinz Wiendl received compensation for serving on Scientific Advisory Boards/Steering Committees, for Bayer Healthcare, Biogen Idec, Sanofi Genzyme, Merck Serono and Novartis, lecturing honoraria and travel reimbursements from Bayer Vital, Bayer Schering, Biogen, CSL Behring, EMD Serono, Fresenius Medical Care, Sanofi Genzyme, Merck Serono, Omniamed, Novartis and Sanofi Aventis, compensation as a consultant from Biogen Idec, Merck Serono, Novartis, Roche and Sanofi Genzyme, financial research support from Bayer Healthcare, Bayer Vital, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, Sanofi US and TEVA Pharma.
Sven G. Meuth received lecturing honoraria, travel reimbursements and financial research support from Bayer, Bayer Schering, Biogen Idec, Sanofi Genzyme, Merck Serono, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi-Aventis and Teva.