Contributions
Abstract: P690
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: TOPIC (NCT00622700) evaluated the efficacy and safety of teriflunomide, a once-daily oral immunomodulator, approved for relapsing forms of MS (RMS), in patients with a first clinical episode suggestive of MS (N=614). Patients completing TOPIC, still on-study at completion, or experiencing relapse determining conversion to clinically definite MS (CDMS; primary endpoint), were eligible to enrol in an extension, which continued until teriflunomide was locally reimbursed.
Objective: To report clinical outcomes from patients in the TOPIC extension study throughout completion (up to 7 years of treatment).
Methods: In TOPIC, patients received placebo or teriflunomide 7 mg or 14 mg for ≤108 weeks. In the extension, teriflunomide-treated patients continued to receive their original dose; the placebo group was re-randomized 1:1 to teriflunomide 7 mg or 14 mg. Safety data are reported for the extension period; clinical data are reported for core plus extension periods.
Results: In the extension, 423 patients were randomized and treated. Cumulative teriflunomide exposures (from start of core study) were 242, 559, 248, and 606 patient-years for the placebo/7-mg, 7-mg/7-mg, placebo/14-mg, and 14-mg/14-mg groups, respectively. Most patients (75%) completed the extension study; fewer patients receiving the 14-mg dose (20%) vs the 7-mg dose (27.5%) discontinued. Patient choice was the most common reason for discontinuation (43/107 discontinuations). Over the extension period, adverse events (AEs) occurred in 82% of patients. The nature and incidence of AEs were comparable to those in other teriflunomide clinical studies and their extensions. Across groups, annualized relapse rate was ≤0.163, ≥61% of patients remained free from relapse, and ≥78% of patients remained free from disability worsening confirmed for ≥12 weeks (no significant between-group differences). Most patients (≥63% per group) did not experience relapse determining conversion to CDMS. The risk of relapse determining conversion to CDMS was lower in the 14-mg/14-mg (early treatment) group vs the placebo/14-mg (delayed treatment) group (hazard ratio [95% confidence interval] 0.529 [0.317, 0.883], P=0.0149).
Conclusions: Together with data from studies in RMS, observations in patients with a first clinical episode suggestive of MS demonstrate the consistent safety and enduring efficacy during long-term treatment with teriflunomide across a range of RMS patient subtypes.
Disclosure: Study supported by Sanofi Genzyme,
AEM: Consulting fees (Accordant Health Services, Acorda Therapeutics, Alkermes, Biogen Idec, EMD Serono, Genentech, Genzyme, GSK, Mallinckrodt Pharmaceuticals [Questcor], Novartis, Roche, Teva); contracted research (Biogen Idec, Genentech, Novartis, Questcor, Roche, Sanofi).
LK: Author´s institution (University Hospital Basel) has received in last 3 years and used exclusively for research support: steering committee, advisory board, and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, XenoPort); speaker fees (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, Teva); support of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva); royalties (Neurostatus Systems GmbH); grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, Swiss National Research Foundation).
GC: Consulting fees (Almirall, Bayer, Chugai, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, Serono Symposia International Foundation [SSIF], Teva); fees from non-CME services (Almirall, Bayer, Biogen, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, SSIF, Teva).
MSF: Research/educational grant support (Bayer HealthCare, Genzyme); honoraria/consulting fees (Bayer HealthCare, Biogen Idec, EMD Canada, Novartis, Sanofi, Teva Canada Innovation); member of company advisory boards/board of directors/other similar group (Bayer HealthCare, Biogen Idec, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, Teva Canada Innovation).
JdS: Consulting services, advisory boards (Genzyme).
JO: Consulting or speaking fees (Biogen Idec, EMD Serono, Genzyme, Novartis, Roche); grant/research support (Biogen Idec, Genzyme, MS Society of Canada).
PT: Employee of Sanofi Genzyme, with ownership interest.
MB: Employee of Sanofi Genzyme.
AP: Employee of Sanofi Genzyme.
JSW: Within the last 3 years, consulting agreements (AbbVie, Actelion, Alkermes, Athersys, Inc., Bayer HeathCare, EMD Serono, Forward Pharma, Genzyme, Novartis, Roche, Taketa, Teva, XenoPort); contracted research (Genzyme, National Institutes of Health, National MS Society); royalties (for monoclonal antibodies out-licensed to Chemicon International), through the University of Texas Health Science Center at Houston.
Abstract: P690
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: TOPIC (NCT00622700) evaluated the efficacy and safety of teriflunomide, a once-daily oral immunomodulator, approved for relapsing forms of MS (RMS), in patients with a first clinical episode suggestive of MS (N=614). Patients completing TOPIC, still on-study at completion, or experiencing relapse determining conversion to clinically definite MS (CDMS; primary endpoint), were eligible to enrol in an extension, which continued until teriflunomide was locally reimbursed.
Objective: To report clinical outcomes from patients in the TOPIC extension study throughout completion (up to 7 years of treatment).
Methods: In TOPIC, patients received placebo or teriflunomide 7 mg or 14 mg for ≤108 weeks. In the extension, teriflunomide-treated patients continued to receive their original dose; the placebo group was re-randomized 1:1 to teriflunomide 7 mg or 14 mg. Safety data are reported for the extension period; clinical data are reported for core plus extension periods.
Results: In the extension, 423 patients were randomized and treated. Cumulative teriflunomide exposures (from start of core study) were 242, 559, 248, and 606 patient-years for the placebo/7-mg, 7-mg/7-mg, placebo/14-mg, and 14-mg/14-mg groups, respectively. Most patients (75%) completed the extension study; fewer patients receiving the 14-mg dose (20%) vs the 7-mg dose (27.5%) discontinued. Patient choice was the most common reason for discontinuation (43/107 discontinuations). Over the extension period, adverse events (AEs) occurred in 82% of patients. The nature and incidence of AEs were comparable to those in other teriflunomide clinical studies and their extensions. Across groups, annualized relapse rate was ≤0.163, ≥61% of patients remained free from relapse, and ≥78% of patients remained free from disability worsening confirmed for ≥12 weeks (no significant between-group differences). Most patients (≥63% per group) did not experience relapse determining conversion to CDMS. The risk of relapse determining conversion to CDMS was lower in the 14-mg/14-mg (early treatment) group vs the placebo/14-mg (delayed treatment) group (hazard ratio [95% confidence interval] 0.529 [0.317, 0.883], P=0.0149).
Conclusions: Together with data from studies in RMS, observations in patients with a first clinical episode suggestive of MS demonstrate the consistent safety and enduring efficacy during long-term treatment with teriflunomide across a range of RMS patient subtypes.
Disclosure: Study supported by Sanofi Genzyme,
AEM: Consulting fees (Accordant Health Services, Acorda Therapeutics, Alkermes, Biogen Idec, EMD Serono, Genentech, Genzyme, GSK, Mallinckrodt Pharmaceuticals [Questcor], Novartis, Roche, Teva); contracted research (Biogen Idec, Genentech, Novartis, Questcor, Roche, Sanofi).
LK: Author´s institution (University Hospital Basel) has received in last 3 years and used exclusively for research support: steering committee, advisory board, and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, XenoPort); speaker fees (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, Teva); support of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva); royalties (Neurostatus Systems GmbH); grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, Swiss National Research Foundation).
GC: Consulting fees (Almirall, Bayer, Chugai, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, Serono Symposia International Foundation [SSIF], Teva); fees from non-CME services (Almirall, Bayer, Biogen, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, SSIF, Teva).
MSF: Research/educational grant support (Bayer HealthCare, Genzyme); honoraria/consulting fees (Bayer HealthCare, Biogen Idec, EMD Canada, Novartis, Sanofi, Teva Canada Innovation); member of company advisory boards/board of directors/other similar group (Bayer HealthCare, Biogen Idec, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, Teva Canada Innovation).
JdS: Consulting services, advisory boards (Genzyme).
JO: Consulting or speaking fees (Biogen Idec, EMD Serono, Genzyme, Novartis, Roche); grant/research support (Biogen Idec, Genzyme, MS Society of Canada).
PT: Employee of Sanofi Genzyme, with ownership interest.
MB: Employee of Sanofi Genzyme.
AP: Employee of Sanofi Genzyme.
JSW: Within the last 3 years, consulting agreements (AbbVie, Actelion, Alkermes, Athersys, Inc., Bayer HeathCare, EMD Serono, Forward Pharma, Genzyme, Novartis, Roche, Taketa, Teva, XenoPort); contracted research (Genzyme, National Institutes of Health, National MS Society); royalties (for monoclonal antibodies out-licensed to Chemicon International), through the University of Texas Health Science Center at Houston.