The Experts below are selected from a list of 846 Experts worldwide ranked by ideXlab platform
Mark S. Freedman - One of the best experts on this subject based on the ideXlab platform.
-
ponesimod compared with Teriflunomide in patients with relapsing multiple sclerosis in the active comparator phase 3 optimum study a randomized clinical trial
JAMA Neurology, 2021Co-Authors: Ludwig Kappos, Mark S. Freedman, Eva Havrdova, Xavier Montalban, Fred D Lublin, Robert J Fox, Michel Burcklen, Brian Hennessy, Reinhard Hohlfeld, Carlo PozzilliAbstract:Importance To our knowledge, the Oral Ponesimod Versus Teriflunomide In Relapsing Multiple Sclerosis (OPTIMUM) trial is the first phase 3 study comparing 2 oral disease-modifying therapies for relapsing multiple sclerosis (RMS). Objective To compare the efficacy of ponesimod, a selective sphingosine-1-phosphate receptor 1 (S1P1) modulator with Teriflunomide, a pyrimidine synthesis inhibitor, approved for the treatment of patients with RMS. Design, Setting, and Participants This multicenter, double-blind, active-comparator, superiority randomized clinical trial enrolled patients from April 27, 2015, to May 16, 2019, who were aged 18 to 55 years and had been diagnosed with multiple sclerosis per 2010 McDonald criteria, with a relapsing course from the onset, Expanded Disability Status Scale (EDSS) scores of 0 to 5.5, and recent clinical or magnetic resonance imaging disease activity. Interventions Patients were randomized (1:1) to 20 mg of ponesimod or 14 mg of Teriflunomide once daily and the placebo for 108 weeks, with a 14-day gradual up-titration of ponesimod starting at 2 mg to mitigate first-dose cardiac effects of S1P1modulators and a follow-up period of 30 days. Main Outcomes and Measures The primary end point was the annualized relapse rate. The secondary end points were the changes in symptom domain of Fatigue Symptom and Impact Questionnaire–Relapsing Multiple Sclerosis (FSIQ–RMS) at week 108, the number of combined unique active lesions per year on magnetic resonance imaging, and time to 12-week and 24-week confirmed disability accumulation. Safety and tolerability were assessed. Exploratory end points included the percentage change in brain volume and no evidence of disease activity (NEDA-3 and NEDA-4) status. Results For 1133 patients (567 receiving ponesimod and 566 receiving Teriflunomide; median [range], 37.0 [18-55] years; 735 women [64.9%]), the relative rate reduction for ponesimod vs Teriflunomide in the annualized relapse rate was 30.5% (0.202 vs 0.290;P Conclusions and Relevance In this study, ponesimod was superior to Teriflunomide on annualized relapse rate reduction, fatigue, magnetic resonance imaging activity, brain volume loss, and no evidence of disease activity status, but not confirmed disability accumulation. The safety profile was in line with the previous safety observations with ponesimod and the known profile of other S1P receptor modulators. Trial Registration ClinicalTrials.gov Identifier:NCT02425644
-
long term outcomes with Teriflunomide in patients with clinically isolated syndrome results of the topic extension study
Multiple sclerosis and related disorders, 2019Co-Authors: Aaron E. Miller, Ludwig Kappos, Giancarlo Comi, Mark S. Freedman, P. Truffinet, Myriam Benamor, Jerome De Seze, Patrick Vermersch, Annie Purvis, Jerry S. WolinskyAbstract:Abstract Background In the phase 3 TOPIC study, Teriflunomide significantly reduced the risk of relapse determining conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome, versus placebo. We assessed clinical and safety outcomes associated with extended Teriflunomide treatment in the TOPIC extension study. Methods Patients who completed the TOPIC core study (including those still on study at early termination) or converted to CDMS after at least 24 weeks in the core study were eligible to participate in the extension. The primary efficacy endpoint in the extension was time to conversion to CDMS. Results Risk of relapse determining conversion to CDMS was 47.1% lower in patients treated with Teriflunomide 14 mg during the core and extension studies compared with patients treated with placebo during the core study and Teriflunomide 14 mg during the extension. The incidence of adverse events was 75.8% and 81.9% for 7 and 14 mg Teriflunomide, respectively. Conclusions Reduced risk of relapse determining conversion to CDMS in patients with early MS receiving Teriflunomide 14 mg in the core study remained throughout the extension supporting the benefits of early treatment. No new safety signals were observed for Teriflunomide 7 or 14 mg.
-
long term disability outcomes in patients treated with Teriflunomide for up to 14 years group and patient level data from the phase 2 extension study p6 389
Neurology, 2018Co-Authors: Mark S. Freedman, P. Truffinet, Myriam Benamor, Amit Baror, Matt Mandel, Elizabeth Poole, Marcelo KremenchutzkyAbstract:Objective: To report long-term outcomes, including patient-level data, for patients who continued in the Teriflunomide phase 2 extension (NCT00228163) study until final study termination (up to 14 years of treatment exposure). Background: In the phase 2 extension, disease activity, as measured by MRI and annualized relapse rate, remained low in patients who continued Teriflunomide treatment for up to 14 years. Here, we report long-term disability outcomes. Design/Methods: In the 36-week placebo-controlled core study (NCT01487096), patients with relapsing MS were randomized (1:1:1) to placebo, Teriflunomide 7 mg, or Teriflunomide 14 mg. In the extension, patients initially receiving placebo were re-randomized (1:1) to Teriflunomide 7 mg or 14 mg; patients initially receiving Teriflunomide continued the same dose. Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity (MSS) scores were assessed at baseline, every 12 weeks until core study end, and then every 24 weeks throughout the extension. Results: A total of 173 patients were exposed to Teriflunomide at any point during the core and extension studies. Cumulative duration of exposure was 1136 patient-years. Mean EDSS scores for patients ever exposed to Teriflunomide 14 mg were as follows: baseline, 2.45 (n=83); Year 5, 2.21 (n=42); Year 10, 2.14 (n=32). After Year 10, although patient numbers were small, EDSS scores remained stable. In 69.5% of patients, EDSS scores were stable or improved vs baseline at the last evaluation. Individual EDSS score changes for patients still on study at termination will be presented. Mean MSS scores decreased over the course of the extension (vs baseline) in patients ever exposed to Teriflunomide 14 mg: Year 5, 3.23 (0.54-point reduction); Year 10, 2.17 (1.32-point reduction). Conclusions: EDSS scores remained stable or improved through to the last evaluation for the majority of patients receiving Teriflunomide. MSS scores, indicative of the rate of disability worsening over time, decreased over the course of the extension. Study Supported by: Sanofi Disclosure: Dr. Freedman has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer Healthcare, Biogen, Canada Innovation, Chugai, Clene Nanomedicine, EMD Canada, Hoffman-La Roche, Merck Serono, Novartis, Opexa, Sanofi Aventis, Sanofi Genzyme, and Teva. Dr. Bar-Or has nothing to disclose. Dr. Benamor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Truffinet has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi, with ownership interest. Dr. Truffinet has received compensation for serving on the Board of Directors of Employee of Sanofi, with ownership interest. Dr. Poole has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Mandel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi, with ownership interest. Dr. Mandel has received compensation for serving on the Board of Directors of Employee of Sanofi, with ownership interest. Dr. Kremenchutzky has nothing to disclose.
-
long term efficacy and safety outcomes of Teriflunomide treatment in temso and tower p6 391
Neurology, 2018Co-Authors: Mark S. Freedman, Myriam Benamor, Jeffrey Chavin, Elizabeth M Poole, Giancarlo ComiAbstract:Objective: To report long-term efficacy and safety outcomes in a pooled analysis of data from TEMSO and TOWER and their extension studies. Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing forms of MS (RMS). The efficacy of Teriflunomide has been demonstrated in 2 phase 3 placebo-controlled studies (TEMSO [NCT00134563] and TOWER [NCT00751881]) and their extensions (TEMSO extension [NCT00803049]), in patients with RMS. Long-term treatment with agents that target the immune system may be associated with increased risk of adverse events (AEs). Available evidence suggests Teriflunomide does not significantly impact protective immunity. Design/Methods: Efficacy and safety data were pooled from the TEMSO and TOWER core and extension studies. Overall annualized relapse rates (ARRs), yearly ARRs, yearly proportion of patients free from relapse, and overall AE rates are presented. Results: A total of 1354 patients treated with Teriflunomide 14mg were included in the pooled analyses, with a total of 4460.5 patient-years of cumulative Teriflunomide exposure. Overall ARR during Teriflunomide treatment was 0.24, and yearly ARR ranged from 0.09 to 0.33. The proportion of patients remaining free from relapse ranged from 75.3% to 94.3% per year of follow-up. Overall, 1183 patients (87.4%) receiving Teriflunomide 14mg reported ≥1 AE; most were mild to moderate in nature. A total of 244 (18.0%) patients experienced serious AEs and 193 (14.3%) experienced AEs leading to permanent treatment discontinuation. Detailed data on AEs will be presented. Results of the pooled analysis for the 7-mg dose were generally consistent with those for the 14-mg dose. Conclusions: Overall and yearly ARRs were low and stable, and yearly proportions of patients free from relapse were high and stable, for patients receiving Teriflunomide over long-term follow-up. No new safety signals were reported; serious AEs were uncommon and few led to treatment discontinuation. These data demonstrate the long-term efficacy and safety of Teriflunomide. Study Supported by: Sanofi. Disclosure: Dr. Oh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting or speaking fees (Biogen Idec, EMD Serono, Genzyme, Novartis, Roche). Dr. Oh has received research support from Grant/research support (Biogen Idec, Genzyme, MS Society of Canada, Teva). Dr. Freedman has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer Healthcare, Biogen, Canada Innovation, Chugai, Clene Nanomedicine, EMD Canada, Hoffman-La Roche, Merck Serono, Novartis, Opexa, Sanofi Aventis, Sanofi Genzyme, and Teva. Dr. Benamor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Poole has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Chavin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Comi has nothing to disclose.
-
the efficacy of Teriflunomide in patients who received prior disease modifying treatments subgroup analyses of the Teriflunomide phase 3 temso and tower studies
Multiple Sclerosis Journal, 2018Co-Authors: Mark S. Freedman, Ludwig Kappos, Tomas Olsson, Jerry S. Wolinsky, Giancarlo Comi, Aaron E. Miller, P. Truffinet, Myriam Benamor, Karthinathan Thangavelu, Paul OconnorAbstract:Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (MS). The objective of this post hoc analysis of the phase 3, pooled TEMSO (NCT00134563) and TOWER (NCT00751881) dataset is to evaluate the effect of Teriflunomide treatment on annualised relapse rate and disability worsening across patient subgroups defined according to prior disease-modifying therapy exposure. This analysis provides further supportive evidence for a consistent effect of Teriflunomide across a broad range of patients with relapsing MS, including patients who have used and discontinued other disease-modifying therapies.
Paul Oconnor - One of the best experts on this subject based on the ideXlab platform.
-
the efficacy of Teriflunomide in patients who received prior disease modifying treatments subgroup analyses of the Teriflunomide phase 3 temso and tower studies
Multiple Sclerosis Journal, 2018Co-Authors: Mark S. Freedman, Ludwig Kappos, Tomas Olsson, Jerry S. Wolinsky, Giancarlo Comi, Aaron E. Miller, P. Truffinet, Myriam Benamor, Karthinathan Thangavelu, Paul OconnorAbstract:Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (MS). The objective of this post hoc analysis of the phase 3, pooled TEMSO (NCT00134563) and TOWER (NCT00751881) dataset is to evaluate the effect of Teriflunomide treatment on annualised relapse rate and disability worsening across patient subgroups defined according to prior disease-modifying therapy exposure. This analysis provides further supportive evidence for a consistent effect of Teriflunomide across a broad range of patients with relapsing MS, including patients who have used and discontinued other disease-modifying therapies.
-
early vs delayed treatment with Teriflunomide 14 mg results in reduced risk of disability progression in patients with ms p3 021
Neurology, 2016Co-Authors: Paul Oconnor, Karthinathan Thangavelu, Pascal Rufi, P. TruffinetAbstract:Objective: To investigate effects of early vs delayed treatment initiation with Teriflunomide 14 mg on disability progression, using data from TOWER (NCT00751881) and its extension. Background: TOWER, a randomized, placebo-controlled study of Teriflunomide in patients with relapsing MS (RMS), demonstrated a 31.5[percnt] reduction (P=0.0442) in risk of disability progression confirmed for ≥12 weeks for Teriflunomide 14 mg vs placebo. Patients completing the core TOWER study could enter its extension; patients receiving Teriflunomide 14 mg continued treatment (early treatment) while placebo-treated patients switched to Teriflunomide 14 mg (delayed treatment). Methods: In TOWER, patients with RMS were randomized 1:1:1 to receive placebo or Teriflunomide 14 mg or 7 mg, and treatment lasted ≥48 weeks. In the extension (not powered a priori to compare early vs delayed treatment), all patients received Teriflunomide 14 mg. We compared risk of disability progression confirmed for ≥12 weeks for early vs delayed treatment, using a cutoff date of July 31, 2014 (up to 5.5 years9 total study treatment). Results: Of 750 patients entering the extension, 232 continued with Teriflunomide 14 mg, and 253 switched from placebo to Teriflunomide 14 mg. The percentage of patients with disability progression confirmed for ≥12 weeks was consistently lower in the early vs delayed treatment group. During the core and extension studies, an estimated 26.7[percnt] and 30.2[percnt] of patients experienced disability progression confirmed for ≥12 weeks in the early and delayed treatment groups, respectively. The overall reduction in risk of disability progression confirmed for ≥12 weeks for early vs delayed treatment was 27.6[percnt] (95[percnt] confidence interval: 0.1, 47.5; P=0.0495). Conclusions: We observed a significant reduction in risk of disability progression in patients given early vs delayed treatment with Teriflunomide 14 mg. This highlights the benefit of Teriflunomide for reducing disability progression in patients with MS. Study supported by: Genzyme, a Sanofi company. Disclosure: Dr. O9Connor has received research support from Actelion, Bayer, Biogen Idec, BioMS, Cognosci, Daiichi Sankyo, EMD Serono, Genentech, Genmab, Novartis, Roche, Sanofi, and Teva. Dr. Thangavelu has received personal compensation for activities with Genzyme as an employee. Dr. Rufi has received personal compensation for activities with Genzyme as an employee. Dr. Truffinet has received personal compensation for activities with Genzyme Corporation as an employee.
-
final outcomes of the Teriflunomide phase 2 extension study 13 years of efficacy and safety results p3 027
Neurology, 2016Co-Authors: Marcelo Kremenchutzky, Mark S. Freedman, P. Truffinet, Myriam Benamor, Amit Baror, Annie Purvis, Paul OconnorAbstract:Objective: To report long-term efficacy and safety data from patients treated with Teriflunomide for up to 13 years in a phase 2 extension study (NCT00228163). Background: Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting MS. In phase 2 and 3 studies, Teriflunomide demonstrated consistent efficacy on clinical and magnetic resonance imaging (MRI) outcomes, with a well-characterized safety and tolerability profile. Design/Methods: In the phase 2 study (NCT01487096), patients with relapsing MS were randomized (1:1:1) to once-daily placebo, Teriflunomide 7mg, or 14mg. After completing the 36-week core study, patients could enter a long-term open-label extension in which patients receiving active therapy continued to receive Teriflunomide, while patients previously treated with placebo were reallocated (1:1) to Teriflunomide 7mg or 14mg. Results from the final analysis of the long-term extension (last patient visit, December 1, 2014) are presented. Results: A total of 147 patients entered the extension, which is now complete; including core and extension phases, patients received Teriflunomide (7mg or 14mg) for up to 669 weeks, with a cumulative duration of exposure of 1136 patient-years. During the extension, annualized relapse rates remained low in all groups (0.188 and 0.256 for 14-mg and 7-mg groups, respectively), and proportion of relapse-free patients remained higher in those receiving Teriflunomide 14mg in the extension (34/66, 51.5[percnt]) vs 7mg (32/81, 39.5[percnt]). Expanded Disability Status Scale (EDSS) scores were stable following up to 600 weeks of treatment during the extension. MRI disease activity continued to be low in Teriflunomide-treated patients. No new/unexpected adverse events were identified, and the safety and tolerability profile was consistent with other Teriflunomide clinical studies. Conclusions: Clinical and MRI disease activity remained low and EDSS scores remained stable for up to 13 years of Teriflunomide treatment. No unexpected safety findings were associated with long-term Teriflunomide treatment. Study supported by Genzyme, a Sanofi company. Disclosure: Dr. Kremenchutzky has received research support from Bayer, Biogen Idec, Genzyme, Novartis, Sanofi, and Teva CNS. Dr. Freedman has received research support from Bayer Healthcare and Genzyme. Dr. Bar-Or has received personal compensation for activities with Bayer, Bayhill Therapeutics, Berlex, Biogen Idec, BioMS, Diogenix, Eli Lilly as a consultant, speaker and advisory board member. Dr. Purvis has received personal compensation for activities with Genzyme Corporation. Dr. Benamor has received personal compensation for activities with Genzyme as an employee. Dr. Truffinet has received personal compensation for activities with Genzyme Corporation as an employee. Dr. O9Connor has received research support from Actelion, Bayer, Biogen Idec, BioMS, Cognosci, Daiichi Sankyo, EMD Serono, Genentech, Genmab, Novartis, Roche, Sanofi, and Teva.
-
pooled safety and tolerability data from four placebo controlled Teriflunomide studies and extensions
Multiple sclerosis and related disorders, 2016Co-Authors: Giancarlo Comi, Ludwig Kappos, Tomas Olsson, Jerry S. Wolinsky, Mark S. Freedman, Aaron E. Miller, Myriam Benamor, Paul Oconnor, Deborah Dukovic, P. TruffinetAbstract:Abstract Background Teriflunomide, a once-daily oral immunomodulator for the treatment of relapsing-remitting multiple sclerosis, has demonstrated consistent efficacy on clinical and MRI parameters in clinical trials. Objective To summarize the safety and tolerability profile of Teriflunomide based on data from four placebo-controlled trials. Methods Safety and tolerability were assessed using two Teriflunomide clinical program data pools. Pool 1 contained 3044 patients randomized to Teriflunomide (14 mg or 7 mg) or placebo in the core studies of one phase 2 trial and three phase 3 trials, with cumulative treatment exposure >1500 patient-years per group. Pool 2 comprised 2338 patients who received Teriflunomide treatment in the above trials, including those continuing in extension studies, with a duration of treatment up to 12 years, representing >6800 patient-years. Safety assessments included adverse events, laboratory parameters, and physical examinations. Results In Pool 1, the number of patients experiencing adverse events and serious adverse events was similar in the three treatment groups. Common events occurring in ≥10% of patients in either Teriflunomide group, and with an incidence ≥2% compared with placebo, were alanine aminotransferase (ALT) increase, headache, diarrhea, hair thinning, and nausea. Overall, the nature of events observed in Pool 2 was similar to Pool 1. The majority of events in both pools were of mild-to-moderate intensity, were self-limiting, and infrequently resulted in discontinuation of therapy. The most common reason for treatment discontinuation in all treatment groups was ALT elevation, reflecting the protocol requirement to discontinue treatment on confirmation of ALT>3×the upper limit of normal. Conclusions No new or unexpected safety signals beyond those detected in individual trials were identified in this pooled analysis with treatment duration exceeding 12 years and a cumulative exposure to Teriflunomide exceeding 6800 patient-years. Overall, both doses of Teriflunomide had consistent and manageable safety profiles.
-
a randomized trial of Teriflunomide added to glatiramer acetate in relapsing multiple sclerosis
Multiple Sclerosis Journal – Experimental Translational and Clinical, 2015Co-Authors: Jerry S. Wolinsky, Ludwig Kappos, Tomas Olsson, Aaron E. Miller, P. Truffinet, G. Comi, Myriam Benamor, S Chambers, Paul OconnorAbstract:BackgroundTeriflunomide is a once-daily oral immunomodulator for the treatment of relapsing−remitting MS.ObjectiveTo evaluate the safety and tolerability of Teriflunomide as add-on therapy to a stable dose of glatiramer acetate (GA) in patients with relapsing forms of MS (RMS).MethodsPhase II, randomized, double-blind, add-on, placebo-controlled study. The primary objective was to assess safety and tolerability; secondary objectives were to evaluate effects of treatment on disease activity assessed by MRI and relapse.ResultsPatients with RMS on GA (N = 123) were randomized 1:1:1 to receive Teriflunomide 14 mg (n = 40), 7 mg (n = 42), or placebo (n = 41) for 24 weeks; 96 patients entered the 24-week extension, remaining on original treatment allocation. Teriflunomide was well tolerated over 48 weeks. The frequency of adverse events (AEs) was low across all groups; 5 (12.2%), 3 (7.1%), and 2 (5.0%) patients in the 14 mg, 7 mg, and placebo groups, respectively, discontinued treatment due to AEs. Teriflunomid...
Ludwig Kappos - One of the best experts on this subject based on the ideXlab platform.
-
ponesimod compared with Teriflunomide in patients with relapsing multiple sclerosis in the active comparator phase 3 optimum study a randomized clinical trial
JAMA Neurology, 2021Co-Authors: Ludwig Kappos, Mark S. Freedman, Eva Havrdova, Xavier Montalban, Fred D Lublin, Robert J Fox, Michel Burcklen, Brian Hennessy, Reinhard Hohlfeld, Carlo PozzilliAbstract:Importance To our knowledge, the Oral Ponesimod Versus Teriflunomide In Relapsing Multiple Sclerosis (OPTIMUM) trial is the first phase 3 study comparing 2 oral disease-modifying therapies for relapsing multiple sclerosis (RMS). Objective To compare the efficacy of ponesimod, a selective sphingosine-1-phosphate receptor 1 (S1P1) modulator with Teriflunomide, a pyrimidine synthesis inhibitor, approved for the treatment of patients with RMS. Design, Setting, and Participants This multicenter, double-blind, active-comparator, superiority randomized clinical trial enrolled patients from April 27, 2015, to May 16, 2019, who were aged 18 to 55 years and had been diagnosed with multiple sclerosis per 2010 McDonald criteria, with a relapsing course from the onset, Expanded Disability Status Scale (EDSS) scores of 0 to 5.5, and recent clinical or magnetic resonance imaging disease activity. Interventions Patients were randomized (1:1) to 20 mg of ponesimod or 14 mg of Teriflunomide once daily and the placebo for 108 weeks, with a 14-day gradual up-titration of ponesimod starting at 2 mg to mitigate first-dose cardiac effects of S1P1modulators and a follow-up period of 30 days. Main Outcomes and Measures The primary end point was the annualized relapse rate. The secondary end points were the changes in symptom domain of Fatigue Symptom and Impact Questionnaire–Relapsing Multiple Sclerosis (FSIQ–RMS) at week 108, the number of combined unique active lesions per year on magnetic resonance imaging, and time to 12-week and 24-week confirmed disability accumulation. Safety and tolerability were assessed. Exploratory end points included the percentage change in brain volume and no evidence of disease activity (NEDA-3 and NEDA-4) status. Results For 1133 patients (567 receiving ponesimod and 566 receiving Teriflunomide; median [range], 37.0 [18-55] years; 735 women [64.9%]), the relative rate reduction for ponesimod vs Teriflunomide in the annualized relapse rate was 30.5% (0.202 vs 0.290;P Conclusions and Relevance In this study, ponesimod was superior to Teriflunomide on annualized relapse rate reduction, fatigue, magnetic resonance imaging activity, brain volume loss, and no evidence of disease activity status, but not confirmed disability accumulation. The safety profile was in line with the previous safety observations with ponesimod and the known profile of other S1P receptor modulators. Trial Registration ClinicalTrials.gov Identifier:NCT02425644
-
long term safety and efficacy of Teriflunomide in patients with relapsing multiple sclerosis results from the tower extension study
Multiple sclerosis and related disorders, 2020Co-Authors: Aaron E. Miller, Ludwig Kappos, Tomas Olsson, Jerry S. Wolinsky, Giancarlo Comi, P. Truffinet, Alex L Lublin, Jeffrey Chavin, Jeanluc Delhay, Myriam BenamorAbstract:Abstract Background In the phase 3 TOWER core study (NCT00751881), the efficacy and safety of Teriflunomide compared with placebo were demonstrated in patients with relapsing forms of multiple sclerosis (RMS). Here, the long-term safety and efficacy outcomes from the TOWER extension study (NCT00751881) are reported. Methods All patients who entered the extension (N = 751) were assigned to Teriflunomide 14 mg and assessed for long-term safety and efficacy. Results Of 751 patients in the TOWER extension study, 253, 265, and 233 patients received placebo/Teriflunomide 14 mg, Teriflunomide 7 mg/14 mg, and Teriflunomide 14 mg/14 mg, respectively. Median Teriflunomide exposure was 4.25 years (maximum 6.3 years). The overall frequency of adverse events (AEs) was comparable across treatment groups, but a higher proportion of patients in the Teriflunomide 7 mg/14 mg (12.4%) and 14 mg/14 mg (12.4%) groups had serious AEs compared with the placebo/Teriflunomide 14 mg group (6.4%). Alanine aminotransferase increase and hair thinning occurred at a higher frequency in the placebo/Teriflunomide 14 mg group (11.2% and 14.3%, respectively) compared with the Teriflunomide 7 mg/14 mg (3.0% and 4.5%, respectively) and 14 mg/14 mg groups (5.2% and 4.3%, respectively). The incidences of AEs of interest (hematologic and hepatic effects, peripheral neuropathy, hypertension, and malignancy) were low and comparable across treatment arms. Disability worsening and adjusted annualized relapse rates were low and stable over time, and mean Expanded Disability Status Scale scores were unchanged over time, for all treatment groups. Conclusion In the TOWER extension study, the efficacy of Teriflunomide 14 mg was maintained in patients with RMS. No new or unexpected AEs were observed with Teriflunomide treatment, supporting a safety profile in the extension that was consistent with the core trial. These findings support the positive benefit:risk profile of Teriflunomide as a long-term immunomodulatory therapy.
-
long term outcomes with Teriflunomide in patients with clinically isolated syndrome results of the topic extension study
Multiple sclerosis and related disorders, 2019Co-Authors: Aaron E. Miller, Ludwig Kappos, Giancarlo Comi, Mark S. Freedman, P. Truffinet, Myriam Benamor, Jerome De Seze, Patrick Vermersch, Annie Purvis, Jerry S. WolinskyAbstract:Abstract Background In the phase 3 TOPIC study, Teriflunomide significantly reduced the risk of relapse determining conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome, versus placebo. We assessed clinical and safety outcomes associated with extended Teriflunomide treatment in the TOPIC extension study. Methods Patients who completed the TOPIC core study (including those still on study at early termination) or converted to CDMS after at least 24 weeks in the core study were eligible to participate in the extension. The primary efficacy endpoint in the extension was time to conversion to CDMS. Results Risk of relapse determining conversion to CDMS was 47.1% lower in patients treated with Teriflunomide 14 mg during the core and extension studies compared with patients treated with placebo during the core study and Teriflunomide 14 mg during the extension. The incidence of adverse events was 75.8% and 81.9% for 7 and 14 mg Teriflunomide, respectively. Conclusions Reduced risk of relapse determining conversion to CDMS in patients with early MS receiving Teriflunomide 14 mg in the core study remained throughout the extension supporting the benefits of early treatment. No new safety signals were observed for Teriflunomide 7 or 14 mg.
-
068 evaluation of the long term treatment effect of Teriflunomide on cognitive outcomes and association with brain volume change data from temso and its extension study
Journal of Neurology Neurosurgery and Psychiatry, 2018Co-Authors: Till Sprenger, Jerry S. Wolinsky, Karthinathan Thangavelu, Jens Wuerfel, Matt Mandel, Jeannette Lechnerscott, Maria Pia Sormani, Steven Cavalier, Ludwig KapposAbstract:Introduction In a blinded SIENA (Structural Image Evaluation using Normalisation of Atrophy) analysis of TEMSO (NCT00134563), Teriflunomide significantly reduced brain volume loss (BVL) over 2 years vs placebo. Further analysis indicated a strong correlation between 2 year BVL and disability worsening, showing better disability outcomes for patients with lower rates of BVL. Here, we explore the relationship between BVL and long-term changes in cognitive function in TEMSO and its extension (NCT00803049). Methods The effect of Teriflunomide on cognitive function was assessed by change from baseline in Paced Auditory Serial Addition Test (PASAT)−3 scores in the TEMSO core (n=1086) and extension (n=740) studies. To evaluate change in PASAT-3 scores over 5 years, the TEMSO population was categorised into groups defined by percentage brain volume change from baseline to Year 2 (assessed by SIENA). Results Adjusted mean changes from baseline to Week 96 in PASAT-3 raw/Z-scores were –0.265/–0.022 and 0.870/0.073 for placebo and Teriflunomide 14 mg, respectively (difference vs placebo, p=0.0435 in both instances). Long-term improvements in PASAT-3 Z-scores were observed with Teriflunomide 14 mg treatment: mean (SD) changes from baseline at Weeks 156 and 276 were 0.194 (0.634) and 0.200 (0.677), respectively. Mean (SD) units of change from baseline in raw PASAT-3 scores for Teriflunomide 14 mg–treated patients at Weeks 156 and 276 were 2.36 (7.73) and 2.43 (8.24), respectively. In an association analysis, the group with least BVL from baseline to Year 2 demonstrated a significant improvement in PASAT-3 score with Teriflunomide treatment over 5 years vs the group with most BVL. Conclusion Teriflunomide significantly improved PASAT-3 performance vs placebo over 5 years in the TEMSO core and extension studies. Slower rates of BVL over 2 years correlated with better long-term PASAT-3 improvement. This study suggests that BVL earlier in the disease course predicts longer-term cognitive function. Study support Sanofi.
-
the efficacy of Teriflunomide in patients who received prior disease modifying treatments subgroup analyses of the Teriflunomide phase 3 temso and tower studies
Multiple Sclerosis Journal, 2018Co-Authors: Mark S. Freedman, Ludwig Kappos, Tomas Olsson, Jerry S. Wolinsky, Giancarlo Comi, Aaron E. Miller, P. Truffinet, Myriam Benamor, Karthinathan Thangavelu, Paul OconnorAbstract:Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (MS). The objective of this post hoc analysis of the phase 3, pooled TEMSO (NCT00134563) and TOWER (NCT00751881) dataset is to evaluate the effect of Teriflunomide treatment on annualised relapse rate and disability worsening across patient subgroups defined according to prior disease-modifying therapy exposure. This analysis provides further supportive evidence for a consistent effect of Teriflunomide across a broad range of patients with relapsing MS, including patients who have used and discontinued other disease-modifying therapies.
P. Truffinet - One of the best experts on this subject based on the ideXlab platform.
-
long term safety and efficacy of Teriflunomide in patients with relapsing multiple sclerosis results from the tower extension study
Multiple sclerosis and related disorders, 2020Co-Authors: Aaron E. Miller, Ludwig Kappos, Tomas Olsson, Jerry S. Wolinsky, Giancarlo Comi, P. Truffinet, Alex L Lublin, Jeffrey Chavin, Jeanluc Delhay, Myriam BenamorAbstract:Abstract Background In the phase 3 TOWER core study (NCT00751881), the efficacy and safety of Teriflunomide compared with placebo were demonstrated in patients with relapsing forms of multiple sclerosis (RMS). Here, the long-term safety and efficacy outcomes from the TOWER extension study (NCT00751881) are reported. Methods All patients who entered the extension (N = 751) were assigned to Teriflunomide 14 mg and assessed for long-term safety and efficacy. Results Of 751 patients in the TOWER extension study, 253, 265, and 233 patients received placebo/Teriflunomide 14 mg, Teriflunomide 7 mg/14 mg, and Teriflunomide 14 mg/14 mg, respectively. Median Teriflunomide exposure was 4.25 years (maximum 6.3 years). The overall frequency of adverse events (AEs) was comparable across treatment groups, but a higher proportion of patients in the Teriflunomide 7 mg/14 mg (12.4%) and 14 mg/14 mg (12.4%) groups had serious AEs compared with the placebo/Teriflunomide 14 mg group (6.4%). Alanine aminotransferase increase and hair thinning occurred at a higher frequency in the placebo/Teriflunomide 14 mg group (11.2% and 14.3%, respectively) compared with the Teriflunomide 7 mg/14 mg (3.0% and 4.5%, respectively) and 14 mg/14 mg groups (5.2% and 4.3%, respectively). The incidences of AEs of interest (hematologic and hepatic effects, peripheral neuropathy, hypertension, and malignancy) were low and comparable across treatment arms. Disability worsening and adjusted annualized relapse rates were low and stable over time, and mean Expanded Disability Status Scale scores were unchanged over time, for all treatment groups. Conclusion In the TOWER extension study, the efficacy of Teriflunomide 14 mg was maintained in patients with RMS. No new or unexpected AEs were observed with Teriflunomide treatment, supporting a safety profile in the extension that was consistent with the core trial. These findings support the positive benefit:risk profile of Teriflunomide as a long-term immunomodulatory therapy.
-
long term outcomes with Teriflunomide in patients with clinically isolated syndrome results of the topic extension study
Multiple sclerosis and related disorders, 2019Co-Authors: Aaron E. Miller, Ludwig Kappos, Giancarlo Comi, Mark S. Freedman, P. Truffinet, Myriam Benamor, Jerome De Seze, Patrick Vermersch, Annie Purvis, Jerry S. WolinskyAbstract:Abstract Background In the phase 3 TOPIC study, Teriflunomide significantly reduced the risk of relapse determining conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome, versus placebo. We assessed clinical and safety outcomes associated with extended Teriflunomide treatment in the TOPIC extension study. Methods Patients who completed the TOPIC core study (including those still on study at early termination) or converted to CDMS after at least 24 weeks in the core study were eligible to participate in the extension. The primary efficacy endpoint in the extension was time to conversion to CDMS. Results Risk of relapse determining conversion to CDMS was 47.1% lower in patients treated with Teriflunomide 14 mg during the core and extension studies compared with patients treated with placebo during the core study and Teriflunomide 14 mg during the extension. The incidence of adverse events was 75.8% and 81.9% for 7 and 14 mg Teriflunomide, respectively. Conclusions Reduced risk of relapse determining conversion to CDMS in patients with early MS receiving Teriflunomide 14 mg in the core study remained throughout the extension supporting the benefits of early treatment. No new safety signals were observed for Teriflunomide 7 or 14 mg.
-
long term disability outcomes in patients treated with Teriflunomide for up to 14 years group and patient level data from the phase 2 extension study p6 389
Neurology, 2018Co-Authors: Mark S. Freedman, P. Truffinet, Myriam Benamor, Amit Baror, Matt Mandel, Elizabeth Poole, Marcelo KremenchutzkyAbstract:Objective: To report long-term outcomes, including patient-level data, for patients who continued in the Teriflunomide phase 2 extension (NCT00228163) study until final study termination (up to 14 years of treatment exposure). Background: In the phase 2 extension, disease activity, as measured by MRI and annualized relapse rate, remained low in patients who continued Teriflunomide treatment for up to 14 years. Here, we report long-term disability outcomes. Design/Methods: In the 36-week placebo-controlled core study (NCT01487096), patients with relapsing MS were randomized (1:1:1) to placebo, Teriflunomide 7 mg, or Teriflunomide 14 mg. In the extension, patients initially receiving placebo were re-randomized (1:1) to Teriflunomide 7 mg or 14 mg; patients initially receiving Teriflunomide continued the same dose. Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity (MSS) scores were assessed at baseline, every 12 weeks until core study end, and then every 24 weeks throughout the extension. Results: A total of 173 patients were exposed to Teriflunomide at any point during the core and extension studies. Cumulative duration of exposure was 1136 patient-years. Mean EDSS scores for patients ever exposed to Teriflunomide 14 mg were as follows: baseline, 2.45 (n=83); Year 5, 2.21 (n=42); Year 10, 2.14 (n=32). After Year 10, although patient numbers were small, EDSS scores remained stable. In 69.5% of patients, EDSS scores were stable or improved vs baseline at the last evaluation. Individual EDSS score changes for patients still on study at termination will be presented. Mean MSS scores decreased over the course of the extension (vs baseline) in patients ever exposed to Teriflunomide 14 mg: Year 5, 3.23 (0.54-point reduction); Year 10, 2.17 (1.32-point reduction). Conclusions: EDSS scores remained stable or improved through to the last evaluation for the majority of patients receiving Teriflunomide. MSS scores, indicative of the rate of disability worsening over time, decreased over the course of the extension. Study Supported by: Sanofi Disclosure: Dr. Freedman has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer Healthcare, Biogen, Canada Innovation, Chugai, Clene Nanomedicine, EMD Canada, Hoffman-La Roche, Merck Serono, Novartis, Opexa, Sanofi Aventis, Sanofi Genzyme, and Teva. Dr. Bar-Or has nothing to disclose. Dr. Benamor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Truffinet has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi, with ownership interest. Dr. Truffinet has received compensation for serving on the Board of Directors of Employee of Sanofi, with ownership interest. Dr. Poole has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Mandel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi, with ownership interest. Dr. Mandel has received compensation for serving on the Board of Directors of Employee of Sanofi, with ownership interest. Dr. Kremenchutzky has nothing to disclose.
-
the efficacy of Teriflunomide in patients who received prior disease modifying treatments subgroup analyses of the Teriflunomide phase 3 temso and tower studies
Multiple Sclerosis Journal, 2018Co-Authors: Mark S. Freedman, Ludwig Kappos, Tomas Olsson, Jerry S. Wolinsky, Giancarlo Comi, Aaron E. Miller, P. Truffinet, Myriam Benamor, Karthinathan Thangavelu, Paul OconnorAbstract:Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (MS). The objective of this post hoc analysis of the phase 3, pooled TEMSO (NCT00134563) and TOWER (NCT00751881) dataset is to evaluate the effect of Teriflunomide treatment on annualised relapse rate and disability worsening across patient subgroups defined according to prior disease-modifying therapy exposure. This analysis provides further supportive evidence for a consistent effect of Teriflunomide across a broad range of patients with relapsing MS, including patients who have used and discontinued other disease-modifying therapies.
-
predicting long term disability outcomes in patients with ms treated with Teriflunomide in temso
Neuroimmunology and Neuroinflammation, 2017Co-Authors: Maria Pia Sormani, P. Truffinet, Karthinathan Thangavelu, Pascal Rufi, Catherine Simonson, Nicola De StefanoAbstract:OBJECTIVE To predict long-term disability outcomes in TEMSO core (NCT00134563) and extension (NCT00803049) studies in patients with relapsing forms of MS treated with Teriflunomide. METHODS A post hoc analysis was conducted in a subgroup of patients who received Teriflunomide in the core study, had MRI and clinical relapse assessments at months 12 (n = 552) and 18, and entered the extension. Patients were allocated risk scores for disability worsening (DW) after 1 year of Teriflunomide treatment: 0 = low risk; 1 = intermediate risk; and 2-3 = high risk, based on the occurrence of relapses (0 to ≥2) and/or active (new and enlarging) T2-weighted (T2w) lesions (≤3 or >3) after the 1-year MRI. Patients in the intermediate-risk group were reclassified as responders or nonresponders (low or high risk) according to relapses and T2w lesions on the 18-month MRI. Long-term risk (7 years) of DW was assessed by Kaplan-Meier survival curves. RESULTS In patients with a score of 2-3, the risk of 12-week-confirmed DW over 7 years was significantly higher vs those with a score of 0 (hazard ratio [HR] = 1.96, p = 0.0044). Patients reclassified as high risk at month 18 (18.6%) had a significantly higher risk of DW vs those in the low-risk group (81.4%; HR = 1.92; p = 0.0004). CONCLUSIONS Over 80% of patients receiving Teriflunomide were classified as low risk (responders) and had a significantly lower risk of DW than those at increased risk (nonresponders) over 7 years of follow-up in TEMSO. Close monitoring of relapses and active T2w lesions after short-term Teriflunomide treatment predicts a differential rate of subsequent DW long term. CLINICALTRIALSGOV IDENTIFIER TEMSO, NCT00134563; TEMSO extension, NCT00803049.
Jerry S. Wolinsky - One of the best experts on this subject based on the ideXlab platform.
-
long term safety and efficacy of Teriflunomide in patients with relapsing multiple sclerosis results from the tower extension study
Multiple sclerosis and related disorders, 2020Co-Authors: Aaron E. Miller, Ludwig Kappos, Tomas Olsson, Jerry S. Wolinsky, Giancarlo Comi, P. Truffinet, Alex L Lublin, Jeffrey Chavin, Jeanluc Delhay, Myriam BenamorAbstract:Abstract Background In the phase 3 TOWER core study (NCT00751881), the efficacy and safety of Teriflunomide compared with placebo were demonstrated in patients with relapsing forms of multiple sclerosis (RMS). Here, the long-term safety and efficacy outcomes from the TOWER extension study (NCT00751881) are reported. Methods All patients who entered the extension (N = 751) were assigned to Teriflunomide 14 mg and assessed for long-term safety and efficacy. Results Of 751 patients in the TOWER extension study, 253, 265, and 233 patients received placebo/Teriflunomide 14 mg, Teriflunomide 7 mg/14 mg, and Teriflunomide 14 mg/14 mg, respectively. Median Teriflunomide exposure was 4.25 years (maximum 6.3 years). The overall frequency of adverse events (AEs) was comparable across treatment groups, but a higher proportion of patients in the Teriflunomide 7 mg/14 mg (12.4%) and 14 mg/14 mg (12.4%) groups had serious AEs compared with the placebo/Teriflunomide 14 mg group (6.4%). Alanine aminotransferase increase and hair thinning occurred at a higher frequency in the placebo/Teriflunomide 14 mg group (11.2% and 14.3%, respectively) compared with the Teriflunomide 7 mg/14 mg (3.0% and 4.5%, respectively) and 14 mg/14 mg groups (5.2% and 4.3%, respectively). The incidences of AEs of interest (hematologic and hepatic effects, peripheral neuropathy, hypertension, and malignancy) were low and comparable across treatment arms. Disability worsening and adjusted annualized relapse rates were low and stable over time, and mean Expanded Disability Status Scale scores were unchanged over time, for all treatment groups. Conclusion In the TOWER extension study, the efficacy of Teriflunomide 14 mg was maintained in patients with RMS. No new or unexpected AEs were observed with Teriflunomide treatment, supporting a safety profile in the extension that was consistent with the core trial. These findings support the positive benefit:risk profile of Teriflunomide as a long-term immunomodulatory therapy.
-
long term outcomes with Teriflunomide in patients with clinically isolated syndrome results of the topic extension study
Multiple sclerosis and related disorders, 2019Co-Authors: Aaron E. Miller, Ludwig Kappos, Giancarlo Comi, Mark S. Freedman, P. Truffinet, Myriam Benamor, Jerome De Seze, Patrick Vermersch, Annie Purvis, Jerry S. WolinskyAbstract:Abstract Background In the phase 3 TOPIC study, Teriflunomide significantly reduced the risk of relapse determining conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome, versus placebo. We assessed clinical and safety outcomes associated with extended Teriflunomide treatment in the TOPIC extension study. Methods Patients who completed the TOPIC core study (including those still on study at early termination) or converted to CDMS after at least 24 weeks in the core study were eligible to participate in the extension. The primary efficacy endpoint in the extension was time to conversion to CDMS. Results Risk of relapse determining conversion to CDMS was 47.1% lower in patients treated with Teriflunomide 14 mg during the core and extension studies compared with patients treated with placebo during the core study and Teriflunomide 14 mg during the extension. The incidence of adverse events was 75.8% and 81.9% for 7 and 14 mg Teriflunomide, respectively. Conclusions Reduced risk of relapse determining conversion to CDMS in patients with early MS receiving Teriflunomide 14 mg in the core study remained throughout the extension supporting the benefits of early treatment. No new safety signals were observed for Teriflunomide 7 or 14 mg.
-
068 evaluation of the long term treatment effect of Teriflunomide on cognitive outcomes and association with brain volume change data from temso and its extension study
Journal of Neurology Neurosurgery and Psychiatry, 2018Co-Authors: Till Sprenger, Jerry S. Wolinsky, Karthinathan Thangavelu, Jens Wuerfel, Matt Mandel, Jeannette Lechnerscott, Maria Pia Sormani, Steven Cavalier, Ludwig KapposAbstract:Introduction In a blinded SIENA (Structural Image Evaluation using Normalisation of Atrophy) analysis of TEMSO (NCT00134563), Teriflunomide significantly reduced brain volume loss (BVL) over 2 years vs placebo. Further analysis indicated a strong correlation between 2 year BVL and disability worsening, showing better disability outcomes for patients with lower rates of BVL. Here, we explore the relationship between BVL and long-term changes in cognitive function in TEMSO and its extension (NCT00803049). Methods The effect of Teriflunomide on cognitive function was assessed by change from baseline in Paced Auditory Serial Addition Test (PASAT)−3 scores in the TEMSO core (n=1086) and extension (n=740) studies. To evaluate change in PASAT-3 scores over 5 years, the TEMSO population was categorised into groups defined by percentage brain volume change from baseline to Year 2 (assessed by SIENA). Results Adjusted mean changes from baseline to Week 96 in PASAT-3 raw/Z-scores were –0.265/–0.022 and 0.870/0.073 for placebo and Teriflunomide 14 mg, respectively (difference vs placebo, p=0.0435 in both instances). Long-term improvements in PASAT-3 Z-scores were observed with Teriflunomide 14 mg treatment: mean (SD) changes from baseline at Weeks 156 and 276 were 0.194 (0.634) and 0.200 (0.677), respectively. Mean (SD) units of change from baseline in raw PASAT-3 scores for Teriflunomide 14 mg–treated patients at Weeks 156 and 276 were 2.36 (7.73) and 2.43 (8.24), respectively. In an association analysis, the group with least BVL from baseline to Year 2 demonstrated a significant improvement in PASAT-3 score with Teriflunomide treatment over 5 years vs the group with most BVL. Conclusion Teriflunomide significantly improved PASAT-3 performance vs placebo over 5 years in the TEMSO core and extension studies. Slower rates of BVL over 2 years correlated with better long-term PASAT-3 improvement. This study suggests that BVL earlier in the disease course predicts longer-term cognitive function. Study support Sanofi.
-
the efficacy of Teriflunomide in patients who received prior disease modifying treatments subgroup analyses of the Teriflunomide phase 3 temso and tower studies
Multiple Sclerosis Journal, 2018Co-Authors: Mark S. Freedman, Ludwig Kappos, Tomas Olsson, Jerry S. Wolinsky, Giancarlo Comi, Aaron E. Miller, P. Truffinet, Myriam Benamor, Karthinathan Thangavelu, Paul OconnorAbstract:Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (MS). The objective of this post hoc analysis of the phase 3, pooled TEMSO (NCT00134563) and TOWER (NCT00751881) dataset is to evaluate the effect of Teriflunomide treatment on annualised relapse rate and disability worsening across patient subgroups defined according to prior disease-modifying therapy exposure. This analysis provides further supportive evidence for a consistent effect of Teriflunomide across a broad range of patients with relapsing MS, including patients who have used and discontinued other disease-modifying therapies.
-
donnees d extension de l etude topic sur le Teriflunomide chez des patients atteints de sclerose en plaques a un stade precoce resultats cliniques jusqu a 7 ans
Revue Neurologique, 2017Co-Authors: Jerome De Seze, Ludwig Kappos, Giancarlo Comi, Mark S. Freedman, Aaron E. Miller, Jerry S. WolinskyAbstract:Introduction L’etude TOPIC ( NCT00622700 ) a evalue l’efficacite et la tolerance du Teriflunomide chez des patients avec un premier episode clinique evocateur d’une SEP. Apres l’etude, les patients eligibles ont pu entrer dans l’extension. Objectifs Rapporter les resultats cliniques de l’extension de l’etude TOPIC jusqu’a son terme (jusqu’a 7 ans de traitement). Patients et methodes Les patients de TOPIC ont recu un placebo ou du Teriflunomide 7 ou 14 mg jusqu’a 108 semaines. A la fin de TOPIC, les patients toujours dans l’etude ou ayant presente une poussee determinant une conversion en SEP cliniquement definie (SEP-CD ; critere principal) pouvaient etre inclus dans l’extension. Les patients sous Teriflunomide ont recu la meme dose qu’initialement ; ceux sous placebo ont ete re-randomises pour recevoir le Teriflunomide 7 ou 14 mg. Resultats Quatre cent vingt trois patients sont entres dans l’extension. La majorite (75 %) a termine l’etude. La plupart des evenements indesirables etaient d’intensite legere a moderee. Dans chaque groupe, ≥ 63 % des patients n’ont pas presente de poussee determinant une conversion en SEP-CD, avec un risque plus faible dans le groupe 14 mg/14 mg vs placebo/14 mg (HR : 0,529, [IC 95 % : 0,317, 0,883], p = 0,0149). Dans tous les groupes, le taux annualise de poussees etait ≤ 0,163 ; ≥ 61 % des patients n’ont pas presente de poussee. Discussion Ces resultats chez des patients atteints de SEP a un stade precoce confirment ceux des etudes conduites chez des patients atteints de SEP evoluant par poussees. Environ deux tiers des patients n’ont pas presente de progression du handicap confirmee a 12 semaines, pendant une duree de traitement par le Teriflunomide allant jusqu’a 7 ans. Conclusion Le traitement a long terme par le Teriflunomide des patients avec un premier episode clinique evocateur d’une SEP a demontre une securite d’emploi concordante et une efficacite continue. Informations complementaires Etude soutenue par Sanofi Genzyme.
