Contributions
Abstract: P1218
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: The treatment of relapsing remitting multiple sclerosis (RRMS) with natalizumab carries a risk of progressive multifocal leukoencephalopathy (PML). Patients often choose to withdraw natalizumab to mitigate this risk. Patients also switch therapy when natalizumab fails to control disease activity. There is a theoretical risk of carry-over PML when switching from natalizumab to alemtuzumab, and there is a paucity of data to guide neurologists on how to switch patients from natalizumab to alemtuzumab; as well as little previous investigation of efficacy of alemtuzumab in patients who have previously been treated with natalizumab.
Objective: To determine the efficacy and safety of switching from natalizumab to alemtuzumab.
Methods: We retrospectively collected data on patients switching from natalizumab to alemtuzumab at the National Hospital for Neurology and Neurosurgery, London from June 2015 to May 2017.
Results: 14 patients (mean age 40 years, 5 (36%) female) were identified. The median number of natalizumab infusions was 49 (range 8-95). 7 patients switched due to PML risk, 6 due to lack of efficacy and 1 due to desire for pregnancy. The median baseline Expanded Disability Status Scale (EDSS) score before starting alemtuzumab was 6.5 (range 2-8). The median washout period was 117 days (range 28-307). All JCV positive patients had an MRI scan and 7/10 had a lumbar puncture for JCV-DNA PCR prior to switching treatment to exclude sub-clinical PML. To date, 3/14 patients have follow up >1 year and 7/14 have >6 months follow up. Relapses occurred in 3 (21%) patients, all of whom switched to alemtuzumab because of lack of efficacy. EDSS scores remained stable in 8 patients, improved in 3 and worsened in 3 patients. Adverse events were in keeping with the known safety profile of alemtuzumab. There were no cases of PML. Follow-up of this cohort is ongoing.
Conclusions: Alemtuzumab may be an option in patients discontinuing natalizumab due to PML risk. Over half of patients switching from natalizumab to alemtuzumab due to breakthrough disease activity were observed to have relapses within the first 9 months after starting alemtuzumab. Larger studies are required to assess the efficacy and safety of alemtuzumab in patients previously treated with natalizumab, particularly in the subgroup of patients at high risk of PML.
Disclosure:
NA John, A Carroll, A Shields and WJ Brownlee have no conflicts of interest to disclose.
Jeremy Chataway has support from the National Institute of Health Research (NIHR) University College London Hospitals Biomedical Research Centres funding scheme and University College London (UCL). In the last 3 years, he has attended advisory boards for Roche, Merck and Apitope. He is local principal investigator for trials in multiple sclerosis funded by Novartis, Biogen, and Receptos.
Abstract: P1218
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: The treatment of relapsing remitting multiple sclerosis (RRMS) with natalizumab carries a risk of progressive multifocal leukoencephalopathy (PML). Patients often choose to withdraw natalizumab to mitigate this risk. Patients also switch therapy when natalizumab fails to control disease activity. There is a theoretical risk of carry-over PML when switching from natalizumab to alemtuzumab, and there is a paucity of data to guide neurologists on how to switch patients from natalizumab to alemtuzumab; as well as little previous investigation of efficacy of alemtuzumab in patients who have previously been treated with natalizumab.
Objective: To determine the efficacy and safety of switching from natalizumab to alemtuzumab.
Methods: We retrospectively collected data on patients switching from natalizumab to alemtuzumab at the National Hospital for Neurology and Neurosurgery, London from June 2015 to May 2017.
Results: 14 patients (mean age 40 years, 5 (36%) female) were identified. The median number of natalizumab infusions was 49 (range 8-95). 7 patients switched due to PML risk, 6 due to lack of efficacy and 1 due to desire for pregnancy. The median baseline Expanded Disability Status Scale (EDSS) score before starting alemtuzumab was 6.5 (range 2-8). The median washout period was 117 days (range 28-307). All JCV positive patients had an MRI scan and 7/10 had a lumbar puncture for JCV-DNA PCR prior to switching treatment to exclude sub-clinical PML. To date, 3/14 patients have follow up >1 year and 7/14 have >6 months follow up. Relapses occurred in 3 (21%) patients, all of whom switched to alemtuzumab because of lack of efficacy. EDSS scores remained stable in 8 patients, improved in 3 and worsened in 3 patients. Adverse events were in keeping with the known safety profile of alemtuzumab. There were no cases of PML. Follow-up of this cohort is ongoing.
Conclusions: Alemtuzumab may be an option in patients discontinuing natalizumab due to PML risk. Over half of patients switching from natalizumab to alemtuzumab due to breakthrough disease activity were observed to have relapses within the first 9 months after starting alemtuzumab. Larger studies are required to assess the efficacy and safety of alemtuzumab in patients previously treated with natalizumab, particularly in the subgroup of patients at high risk of PML.
Disclosure:
NA John, A Carroll, A Shields and WJ Brownlee have no conflicts of interest to disclose.
Jeremy Chataway has support from the National Institute of Health Research (NIHR) University College London Hospitals Biomedical Research Centres funding scheme and University College London (UCL). In the last 3 years, he has attended advisory boards for Roche, Merck and Apitope. He is local principal investigator for trials in multiple sclerosis funded by Novartis, Biogen, and Receptos.