Contributions
Abstract: EP1727
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Natalizumab (NTZ) has the risk of causing progressive multifocal leukoencephalopathy (PML) in patients after extended use and with detectable anti-JCV-antibodies. There is a need for alternative disease modifying treatment (DMT) that would be safe and effective to prevent recurrence of MS exacerbations upon discontinuation of NTZ without further risk of PML. Platform DMTs have been ineffective in preventing rebound of MS activity. Fingolimod and dimethyl-fumarate (DMF) have associated with PML. No cases of PML have been associated with teriflunomide in 70,000 patients.
Objectives: To explore the safety and efficacy of teriflunomide in patients switching from NTZ to teriflunomide in MS patients at risk for PML.
Methods: Patients with relapsing multiple sclerosis (RMS) must have received 12 or more NTZ treatments and be anti-JCV-ab positive and not have had prior immunosuppressive therapy. Patients had to be free of clinical relapses during prior 12 months of NTZ treatment. RMS patients ages 21 to 65 began teriflunomide at 14mg daily, within 4 weeks after last dose of NTZ. Relapse assessment, EDSS, 3T brain MRI, laboratory tests were performed at baseline and monthly for 6 months. Final assessments were done at 12 months.
Results: There were 62 patients screened and 55 enrolled. Mean age was 47 (SD 10.16). Seventy six percent were female. The mean EDSS at baseline was 3.03 (SD 1.35); 47 patients completed 12 months with mean EDSS of 2.98 (SD 1.44). The mean number of NTZ treatments prior to treatment with teriflunomide was 43 (SD 25.86).
MRI results showed 38 patients (69%) stable in all parameters from baseline to month 12. Seventeen patients had a new MRI lesion during the 12 months. There were 12 patients with Gd+ enhancing lesions, 13 patients with new T2 hyperintensities and 5 patients with enlarging lesions. Most of the patients with new MRI lesions had no symptoms. Only three patients required change of DMT due to MRI progression. Seven patients dropped out of the study due to adverse events or lack of efficacy.
Discussion: These results show that, in the majority of patients, teriflunomide may be a rational choice for long term safety and efficacy for patients at risk for PML. Early switch, in fewer than 4 weeks, from NTZ to teriflunomide, may be important to suppress ongoing ´rebound´ and recurrent MS activity after stopping NTZ.
Disclosure: This study has been supported by an unrestricted educational grant from Genzyme, A Sanofi Company
KE: Received research support from Biogen, Eli Lilly, Genentech, Genzyme, Novartis, Merz Pharmaceuticals;
SC:Serves on steering committees and advisory boards for Biogen, Novartis, Sanofi-Genzyme and Mallinckrodt, receives research support from Biogen, Novartis, Sanofi-Genzyme, Roche, Opexa, and Mallinckrodt, receives speaking honoraria from Biogen, Novartis, Sanofi-Genzyme and Acorda;
JTO, JS, JT, KS, K-KR, CC, TG: Nothing to disclose
Abstract: EP1727
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Natalizumab (NTZ) has the risk of causing progressive multifocal leukoencephalopathy (PML) in patients after extended use and with detectable anti-JCV-antibodies. There is a need for alternative disease modifying treatment (DMT) that would be safe and effective to prevent recurrence of MS exacerbations upon discontinuation of NTZ without further risk of PML. Platform DMTs have been ineffective in preventing rebound of MS activity. Fingolimod and dimethyl-fumarate (DMF) have associated with PML. No cases of PML have been associated with teriflunomide in 70,000 patients.
Objectives: To explore the safety and efficacy of teriflunomide in patients switching from NTZ to teriflunomide in MS patients at risk for PML.
Methods: Patients with relapsing multiple sclerosis (RMS) must have received 12 or more NTZ treatments and be anti-JCV-ab positive and not have had prior immunosuppressive therapy. Patients had to be free of clinical relapses during prior 12 months of NTZ treatment. RMS patients ages 21 to 65 began teriflunomide at 14mg daily, within 4 weeks after last dose of NTZ. Relapse assessment, EDSS, 3T brain MRI, laboratory tests were performed at baseline and monthly for 6 months. Final assessments were done at 12 months.
Results: There were 62 patients screened and 55 enrolled. Mean age was 47 (SD 10.16). Seventy six percent were female. The mean EDSS at baseline was 3.03 (SD 1.35); 47 patients completed 12 months with mean EDSS of 2.98 (SD 1.44). The mean number of NTZ treatments prior to treatment with teriflunomide was 43 (SD 25.86).
MRI results showed 38 patients (69%) stable in all parameters from baseline to month 12. Seventeen patients had a new MRI lesion during the 12 months. There were 12 patients with Gd+ enhancing lesions, 13 patients with new T2 hyperintensities and 5 patients with enlarging lesions. Most of the patients with new MRI lesions had no symptoms. Only three patients required change of DMT due to MRI progression. Seven patients dropped out of the study due to adverse events or lack of efficacy.
Discussion: These results show that, in the majority of patients, teriflunomide may be a rational choice for long term safety and efficacy for patients at risk for PML. Early switch, in fewer than 4 weeks, from NTZ to teriflunomide, may be important to suppress ongoing ´rebound´ and recurrent MS activity after stopping NTZ.
Disclosure: This study has been supported by an unrestricted educational grant from Genzyme, A Sanofi Company
KE: Received research support from Biogen, Eli Lilly, Genentech, Genzyme, Novartis, Merz Pharmaceuticals;
SC:Serves on steering committees and advisory boards for Biogen, Novartis, Sanofi-Genzyme and Mallinckrodt, receives research support from Biogen, Novartis, Sanofi-Genzyme, Roche, Opexa, and Mallinckrodt, receives speaking honoraria from Biogen, Novartis, Sanofi-Genzyme and Acorda;
JTO, JS, JT, KS, K-KR, CC, TG: Nothing to disclose