Contributions
Abstract: P655
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Prolonged natalizumab (NTZ) treatment for relapsing multiple sclerosis (MS) is associated with increased risk of progressive multifocal leukoencephalopathy (PML) in JC virus (JCV) positive patients. Discontinuation of NTZ in JCV-positive patients has been associated with a high risk of relapse in the ensuing 6-12 months, the risk of relapse increasing with duration of post-NTZ “washout”. To date, no known prospective study has demonstrated a therapeutic strategy which reduces the risk of relapse following the discontinuation of NTZ.
Objective: To determine if early introduction of teriflunomide (TFM) will be safe and effective in reducing the risk of disease activity after withdrawing NTZ treatment.
Methods: Adult patients with relapsing MS, who had at least 12 consecutive relapse-free months of NTZ treatment, and the presence of serum anti-JCV antibodies, were switched to TFM within 28 ± 7 days after their last NTZ infusion. Full physical and neurological exam, 3T brain MRI, and labs were performed at baseline, monthly for 6 months, and at 12, 18, and 24 months after initiating TFM. A total of 60 subjects have been screened and 51 of them competed baseline; the results of the 39 subjects who started TFM 6 months or more ago will be reported in this abstract.
Results: 39 subjects, 74.36% female, age 47.74 (± 9.45) years (range 19-63), with a mean baseline EDSS of 3.10 ± 1.28 (range 1.0-6.0) were included in the analysis. Mean duration of prior NTZ treatment was 45.05 ± 25.70 months (range 12-114) and mean duration of TFM therapy was 14.59 ± 5.33 months (range 4-24). 41% of subjects (n=16) had new T2, enlarging T2, or enhancing brain lesions and 10% (n=4) had clinical relapses. Seven subjects had mild hepatic enzyme elevation, and 18 had mild-to-moderate hair loss. No cases of PML have occurred. 4 of the 39 subjects were withdrawn from the study before month 12: 3 had breakthrough disease and 1 had dental infection. As of April 21, 2016, we have observed a non-significant change in EDSS, from 3.15 (±1.34) at baseline to 3.06 (±1.56) at month 12, for the 33 patients who received at least 12 months of TFM therapy.
Conclusion: Our results demonstrate that early initiation of TFM was associated with a 10 % relapse rate following NTZ withdrawal, compared to previously reported rates of 30% or higher, which may be related, in part, to elimination of NTZ washout before initiating TFM therapy, and should inform decisions regarding washout strategies.
Disclosure:
Stanley Cohan serves on steering committees and advisory boards for Biogen, Novartis, Sanofi-Genzyme, Genentech, and Mallinckrodt, receives research support from Biogen, Novartis, Sanofi-Genzyme, Roche, Opexa, and Mallinckrodt, receives speaking honoraria from Biogen, Novartis, Sanofi-Genzyme and Acorda; received support for air travel, lodging and meals from Biogen, Novartis, and Sanofi-Genzyme
Keith Edwards received funding as consultant/advisor/speaker for Biogen & Genzyme and research support from Actelion, Biogen, Eli Lilly, Eisai, Forum Pharmaceuticals, Genentech, Genzyme/Sanofi, Hoffman- La Roche, Novartis, Pfizer, Vaccinex
Kyle Smoot serves on advisory board for Biogen and Teva, received speaking honoraria from Acorda, Biogen, Novartis, Serono, and Teva, and received research support from Biogen
Kiren Kresa Reahl received research support from Biogen and Novartis; received speaking honoraria from Biogen, EMDSerono, Genzyme, Mallinchrodt, Novartis, Pfizer, and Teva.
Tiffany Gervasi received travel support from Merck and TransTech.
Chiayi Chen and Judy O´Connor have nothing to disclose.
Abstract: P655
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Prolonged natalizumab (NTZ) treatment for relapsing multiple sclerosis (MS) is associated with increased risk of progressive multifocal leukoencephalopathy (PML) in JC virus (JCV) positive patients. Discontinuation of NTZ in JCV-positive patients has been associated with a high risk of relapse in the ensuing 6-12 months, the risk of relapse increasing with duration of post-NTZ “washout”. To date, no known prospective study has demonstrated a therapeutic strategy which reduces the risk of relapse following the discontinuation of NTZ.
Objective: To determine if early introduction of teriflunomide (TFM) will be safe and effective in reducing the risk of disease activity after withdrawing NTZ treatment.
Methods: Adult patients with relapsing MS, who had at least 12 consecutive relapse-free months of NTZ treatment, and the presence of serum anti-JCV antibodies, were switched to TFM within 28 ± 7 days after their last NTZ infusion. Full physical and neurological exam, 3T brain MRI, and labs were performed at baseline, monthly for 6 months, and at 12, 18, and 24 months after initiating TFM. A total of 60 subjects have been screened and 51 of them competed baseline; the results of the 39 subjects who started TFM 6 months or more ago will be reported in this abstract.
Results: 39 subjects, 74.36% female, age 47.74 (± 9.45) years (range 19-63), with a mean baseline EDSS of 3.10 ± 1.28 (range 1.0-6.0) were included in the analysis. Mean duration of prior NTZ treatment was 45.05 ± 25.70 months (range 12-114) and mean duration of TFM therapy was 14.59 ± 5.33 months (range 4-24). 41% of subjects (n=16) had new T2, enlarging T2, or enhancing brain lesions and 10% (n=4) had clinical relapses. Seven subjects had mild hepatic enzyme elevation, and 18 had mild-to-moderate hair loss. No cases of PML have occurred. 4 of the 39 subjects were withdrawn from the study before month 12: 3 had breakthrough disease and 1 had dental infection. As of April 21, 2016, we have observed a non-significant change in EDSS, from 3.15 (±1.34) at baseline to 3.06 (±1.56) at month 12, for the 33 patients who received at least 12 months of TFM therapy.
Conclusion: Our results demonstrate that early initiation of TFM was associated with a 10 % relapse rate following NTZ withdrawal, compared to previously reported rates of 30% or higher, which may be related, in part, to elimination of NTZ washout before initiating TFM therapy, and should inform decisions regarding washout strategies.
Disclosure:
Stanley Cohan serves on steering committees and advisory boards for Biogen, Novartis, Sanofi-Genzyme, Genentech, and Mallinckrodt, receives research support from Biogen, Novartis, Sanofi-Genzyme, Roche, Opexa, and Mallinckrodt, receives speaking honoraria from Biogen, Novartis, Sanofi-Genzyme and Acorda; received support for air travel, lodging and meals from Biogen, Novartis, and Sanofi-Genzyme
Keith Edwards received funding as consultant/advisor/speaker for Biogen & Genzyme and research support from Actelion, Biogen, Eli Lilly, Eisai, Forum Pharmaceuticals, Genentech, Genzyme/Sanofi, Hoffman- La Roche, Novartis, Pfizer, Vaccinex
Kyle Smoot serves on advisory board for Biogen and Teva, received speaking honoraria from Acorda, Biogen, Novartis, Serono, and Teva, and received research support from Biogen
Kiren Kresa Reahl received research support from Biogen and Novartis; received speaking honoraria from Biogen, EMDSerono, Genzyme, Mallinchrodt, Novartis, Pfizer, and Teva.
Tiffany Gervasi received travel support from Merck and TransTech.
Chiayi Chen and Judy O´Connor have nothing to disclose.