Contributions
Abstract: P726
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: Sequential use of high-efficacy monoclonal antibodies is commonly encountered in real world practice, but data on its safety and efficacy are rarely available from randomised trials and little guidance is available on how to manage the switch. The pre-licensing use of alemtuzumab in the UK & Ireland (from 1999) provides an opportunity to examine the long term safety and effectiveness of this compound in real world scenarios, including its use after the failure of natalizumab.
Methods: Retrospective clinical and radiographic data are being collected from 18 MS Centres in the UK and Ireland. The aim is to collect all UK and Irish patients switching to alemtuzumab due to natalizumab failure, with centres encouraged to enter data on the switchers with the longest follow-up periods first. 77 patients have been identified to date and preliminary results are presented here on long term safety.
Results: 37 patients had more than 2 years of follow-up data since their first alemtuzumab infusion (mean 4.96 years (SD 1.88, range 2.2-8.0)). Of these, 29 (78.4%) were female, with median age 29.4 years (range 15-61) at diagnosis. Median EDSS at diagnosis was 1.5 (range 0-7). Median duration of disease prior to natalizumab use was 3.9 years (range 0.2-18.5). Mean duration on natalizumab treatment was 1.4 years (median 0.8, range 0.1-5.5). Natalizumab was usually stopped due to lack of efficacy (n=21, 56.8%), hypersensitivity (n=6, 16.2%) and PML risk (n=5, 13.5%). No DMTs were used during the switch period for the majority (n=34, 91.9%). The switch period (from final natalizumab to initial alemtuzumab infusion) lasted a mean of 136 days (median 101, range 28-524). Most subjects received 2 alemtuzumab courses (n=23, 62.2%). No further DMTs were used after alemtuzumab in 33 (89.2%) patients. 18 (48.6%) subjects had one or more infusion reactions and 13 (35.1%) had subsequent adverse events. One serious adverse event (CMV infection) and 1 death from sepsis (1 year after 2nd alemtuzumab course) occurred. The death was considered unrelated to DMTs by the responsible clinician. Autoimmune thyroid disease developed in 6 patients (16.2%). Significant infections occurred in 5 patients (13.5%): VZV (n=3), bacterial (n=1) and CMV (n=1). Thrombocytopaenia occurred in 2 patients (5.4%) and 1 patient (2.7%) developed proteinuria.
Conclusions: No new safety signals were identified in this long term cohort of 37 patients switching to alemtuzumab from natalizumab.
Disclosure: The project was funded by Sanofi Genzyme
Paul Gallagher received salary payment from Sanofi Genzyme for this project and has received travel funding for educational events from this company as well as Novartis and Biogen.
Christopher McGuigan: Consultancy/speaker fees from Biogen, Genzyme, Merck, Novartis & Roche. Research support from Biogen, Novartis and Genzyme
Neil Robertson: Consultancy/speaker fees from Biogen, Sanofi, Genzyme, Novartis, Roche. Research support from Novartis, Biogen and Genzyme
Helen L Ford: In the last year HLF has received consultancy/speaker fees and support to attend educational meetings from Merck, Novartis, Teva and Genzyme
Kate Petheram: Consultancy/travel/speaker fees: Biogen, Roche and Genzyme
Gordon Mazibrada: Consultancy/speaker fees from Biogen, Genzyme, Novartis, Merck-Serono, Teva and Roche. Research support from Novartis, Biogen,Genzyme, Teva and Merck-Serono
Neil Scolding: Nothing to disclose
Joanne Jones: Consultancy and speaker fees from Genzyme
Eli Silber: Support/ hospitality/ fees from Biogen, Genzyme, Merc Serono, Novartis, Roche
Richard Nicholas: Novartis, Genzyme, Biogen Idec honorarium for speaking, advisory boards,Roche - advisory boards, CASTINGS committee member
Owen Pearson: O.R. Pearson served on the scientific advisory board for Biogen, Novartis, Roche, UK MS Register and has received travel funding and/or speaker honoraria from Biogen, Roche, Merck Serono, Novartis, Teva, Genzyme Sanofi.
James Overell has received honoraria for speaking engagements and attendance at advisory boards from Teva, Novartis, Merck-Serono, Genzyme, Roche, Allergan and Biogen. Additionally his department has received educational grants, research funding and funds to provide nursing and administrative staff from these companies.
Abstract: P726
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: Sequential use of high-efficacy monoclonal antibodies is commonly encountered in real world practice, but data on its safety and efficacy are rarely available from randomised trials and little guidance is available on how to manage the switch. The pre-licensing use of alemtuzumab in the UK & Ireland (from 1999) provides an opportunity to examine the long term safety and effectiveness of this compound in real world scenarios, including its use after the failure of natalizumab.
Methods: Retrospective clinical and radiographic data are being collected from 18 MS Centres in the UK and Ireland. The aim is to collect all UK and Irish patients switching to alemtuzumab due to natalizumab failure, with centres encouraged to enter data on the switchers with the longest follow-up periods first. 77 patients have been identified to date and preliminary results are presented here on long term safety.
Results: 37 patients had more than 2 years of follow-up data since their first alemtuzumab infusion (mean 4.96 years (SD 1.88, range 2.2-8.0)). Of these, 29 (78.4%) were female, with median age 29.4 years (range 15-61) at diagnosis. Median EDSS at diagnosis was 1.5 (range 0-7). Median duration of disease prior to natalizumab use was 3.9 years (range 0.2-18.5). Mean duration on natalizumab treatment was 1.4 years (median 0.8, range 0.1-5.5). Natalizumab was usually stopped due to lack of efficacy (n=21, 56.8%), hypersensitivity (n=6, 16.2%) and PML risk (n=5, 13.5%). No DMTs were used during the switch period for the majority (n=34, 91.9%). The switch period (from final natalizumab to initial alemtuzumab infusion) lasted a mean of 136 days (median 101, range 28-524). Most subjects received 2 alemtuzumab courses (n=23, 62.2%). No further DMTs were used after alemtuzumab in 33 (89.2%) patients. 18 (48.6%) subjects had one or more infusion reactions and 13 (35.1%) had subsequent adverse events. One serious adverse event (CMV infection) and 1 death from sepsis (1 year after 2nd alemtuzumab course) occurred. The death was considered unrelated to DMTs by the responsible clinician. Autoimmune thyroid disease developed in 6 patients (16.2%). Significant infections occurred in 5 patients (13.5%): VZV (n=3), bacterial (n=1) and CMV (n=1). Thrombocytopaenia occurred in 2 patients (5.4%) and 1 patient (2.7%) developed proteinuria.
Conclusions: No new safety signals were identified in this long term cohort of 37 patients switching to alemtuzumab from natalizumab.
Disclosure: The project was funded by Sanofi Genzyme
Paul Gallagher received salary payment from Sanofi Genzyme for this project and has received travel funding for educational events from this company as well as Novartis and Biogen.
Christopher McGuigan: Consultancy/speaker fees from Biogen, Genzyme, Merck, Novartis & Roche. Research support from Biogen, Novartis and Genzyme
Neil Robertson: Consultancy/speaker fees from Biogen, Sanofi, Genzyme, Novartis, Roche. Research support from Novartis, Biogen and Genzyme
Helen L Ford: In the last year HLF has received consultancy/speaker fees and support to attend educational meetings from Merck, Novartis, Teva and Genzyme
Kate Petheram: Consultancy/travel/speaker fees: Biogen, Roche and Genzyme
Gordon Mazibrada: Consultancy/speaker fees from Biogen, Genzyme, Novartis, Merck-Serono, Teva and Roche. Research support from Novartis, Biogen,Genzyme, Teva and Merck-Serono
Neil Scolding: Nothing to disclose
Joanne Jones: Consultancy and speaker fees from Genzyme
Eli Silber: Support/ hospitality/ fees from Biogen, Genzyme, Merc Serono, Novartis, Roche
Richard Nicholas: Novartis, Genzyme, Biogen Idec honorarium for speaking, advisory boards,Roche - advisory boards, CASTINGS committee member
Owen Pearson: O.R. Pearson served on the scientific advisory board for Biogen, Novartis, Roche, UK MS Register and has received travel funding and/or speaker honoraria from Biogen, Roche, Merck Serono, Novartis, Teva, Genzyme Sanofi.
James Overell has received honoraria for speaking engagements and attendance at advisory boards from Teva, Novartis, Merck-Serono, Genzyme, Roche, Allergan and Biogen. Additionally his department has received educational grants, research funding and funds to provide nursing and administrative staff from these companies.