Contributions
Abstract: P946
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing forms of MS. In a Phase 2 study (NCT01487096) and two Phase 3 studies (TEMSO [NCT00134563] and TOPIC [NCT00622700]), teriflunomide demonstrated a significant benefit compared with placebo on MRI outcomes including number of gadolinium-enhancing (Gd+) lesions, volume of T1-hypointense lesions and of T2-hyperintense lesions, and unique active lesions, defined as new Gd+ lesions and non-enhancing new/newly enlarging T2-weighted lesions, without double-counting.
Objective: To explore the effect of teriflunomide on unique active lesions in a pooled post hoc analysis of the Phase 2, and Phase 3 TEMSO and TOPIC studies.
Methods: Adult patients with MS (Phase 2 and TEMSO) or a first clinical episode suggestive of MS (TOPIC) were randomized 1:1:1 to receive placebo, teriflunomide 7 mg, or teriflunomide 14 mg. MRI scans were done at baseline and at weeks 6, 12, 18, 24, 30, and 36 (Phase 2); 24, 48, 72, and 108 (TEMSO); and 12, 24, 48, and 108 (TOPIC). Adjusted unique active lesions per scan were estimated using a Poisson model, with corresponding 95% confidence intervals (95% CI). The model was adjusted for treatment, Expanded Disability Status Scale strata at baseline, and region. Log-transformed number of scans was included as an offset variable.
Results: The pooled population comprised 1779 patients, of whom 593, 587, and 599, received placebo, teriflunomide 7 mg, and teriflunomide 14 mg, respectively. The adjusted number of unique active lesions per scan (95% CI) was 3.54 (2.96, 4.24) using all time points (weeks 6 up to 108) in the placebo group, 2.12 (1.68, 2.68) in the teriflunomide 7 mg group, and 1.37 (1.10, 1.70) in the teriflunomide 14 mg group, representing relative risk reductions of 40.2% (P< 0.0001) with teriflunomide 7 mg and 61.4% (P< 0.0001) with teriflunomide 14 mg.
Conclusions: Teriflunomide significantly reduced the risk of unique active lesions compared with placebo, with the largest effect observed in patients treated with teriflunomide 14 mg. Observed reductions in unique active lesions may represent an important indicator of disease activity in MS patients and provides a means to monitor disease activity and treatment response.
Disclosure: AM: Consulting fees from Accordant Health Services, Acorda Therapeutics, Adamas, Alkermes, Biogen, Celgene, EMD Serono, Genentech/Roche, Genzyme, Mallinckrodt Pharmaceuticals [Questcor], Mapi Pharma, Novartis, contracted research for Biogen, Genentech/Roche, Genzyme/Sanofi, Mallickrodt, MedDay, Novartis; Speaker's Bureau: Biogen Idec, EMD Serono, Genentech/Roche (all for unbranded programs only). AR: Personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen, Bracco, Novartis, Sanofi, and Stendhal. CLF: Consulting fees, honoraria, or scientific committee support from Biogen, Genzyme, MedDay, Merck Serono, Novartis, Roche, and Teva. JDS: Personal compensation for activities with Merck, Biogen, Novartis, Roche, Teva, LFB, Alexion, and Sanofi. Research support from LFB and Novartis. YML: Nothing to disclose. DR: Nothing disclosed. RM: Consulting/speaker fees from Bayer, Biogen, Genzyme, Merck Serono, Novartis, Roche, and Sanofi. MK: Research support from the Canadian Institute of Health Research, Chapman Chair in MS clinical research at LHSC, and grants for clinical trials from Biogen, Genzyme, Novartis, and Sanofi. DKBL: Serves on the Data Safety Monitoring Board for Opexa, Scientific Advisory Board for Nuron; acted as a consultant to Genzyme and Novartis; and received research support from EMD Serono, Genzyme, and Roche. AL: Employee of Sanofi with ownership interest. JC: Employee of Sanofi with ownership interest. EP: Employee of Sanofi with ownership interest. AT: Personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Chugai, Roche, Novartis, Sanofi and Teva. Research support from Roche.
Study supported by Sanofi.
Abstract: P946
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing forms of MS. In a Phase 2 study (NCT01487096) and two Phase 3 studies (TEMSO [NCT00134563] and TOPIC [NCT00622700]), teriflunomide demonstrated a significant benefit compared with placebo on MRI outcomes including number of gadolinium-enhancing (Gd+) lesions, volume of T1-hypointense lesions and of T2-hyperintense lesions, and unique active lesions, defined as new Gd+ lesions and non-enhancing new/newly enlarging T2-weighted lesions, without double-counting.
Objective: To explore the effect of teriflunomide on unique active lesions in a pooled post hoc analysis of the Phase 2, and Phase 3 TEMSO and TOPIC studies.
Methods: Adult patients with MS (Phase 2 and TEMSO) or a first clinical episode suggestive of MS (TOPIC) were randomized 1:1:1 to receive placebo, teriflunomide 7 mg, or teriflunomide 14 mg. MRI scans were done at baseline and at weeks 6, 12, 18, 24, 30, and 36 (Phase 2); 24, 48, 72, and 108 (TEMSO); and 12, 24, 48, and 108 (TOPIC). Adjusted unique active lesions per scan were estimated using a Poisson model, with corresponding 95% confidence intervals (95% CI). The model was adjusted for treatment, Expanded Disability Status Scale strata at baseline, and region. Log-transformed number of scans was included as an offset variable.
Results: The pooled population comprised 1779 patients, of whom 593, 587, and 599, received placebo, teriflunomide 7 mg, and teriflunomide 14 mg, respectively. The adjusted number of unique active lesions per scan (95% CI) was 3.54 (2.96, 4.24) using all time points (weeks 6 up to 108) in the placebo group, 2.12 (1.68, 2.68) in the teriflunomide 7 mg group, and 1.37 (1.10, 1.70) in the teriflunomide 14 mg group, representing relative risk reductions of 40.2% (P< 0.0001) with teriflunomide 7 mg and 61.4% (P< 0.0001) with teriflunomide 14 mg.
Conclusions: Teriflunomide significantly reduced the risk of unique active lesions compared with placebo, with the largest effect observed in patients treated with teriflunomide 14 mg. Observed reductions in unique active lesions may represent an important indicator of disease activity in MS patients and provides a means to monitor disease activity and treatment response.
Disclosure: AM: Consulting fees from Accordant Health Services, Acorda Therapeutics, Adamas, Alkermes, Biogen, Celgene, EMD Serono, Genentech/Roche, Genzyme, Mallinckrodt Pharmaceuticals [Questcor], Mapi Pharma, Novartis, contracted research for Biogen, Genentech/Roche, Genzyme/Sanofi, Mallickrodt, MedDay, Novartis; Speaker's Bureau: Biogen Idec, EMD Serono, Genentech/Roche (all for unbranded programs only). AR: Personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen, Bracco, Novartis, Sanofi, and Stendhal. CLF: Consulting fees, honoraria, or scientific committee support from Biogen, Genzyme, MedDay, Merck Serono, Novartis, Roche, and Teva. JDS: Personal compensation for activities with Merck, Biogen, Novartis, Roche, Teva, LFB, Alexion, and Sanofi. Research support from LFB and Novartis. YML: Nothing to disclose. DR: Nothing disclosed. RM: Consulting/speaker fees from Bayer, Biogen, Genzyme, Merck Serono, Novartis, Roche, and Sanofi. MK: Research support from the Canadian Institute of Health Research, Chapman Chair in MS clinical research at LHSC, and grants for clinical trials from Biogen, Genzyme, Novartis, and Sanofi. DKBL: Serves on the Data Safety Monitoring Board for Opexa, Scientific Advisory Board for Nuron; acted as a consultant to Genzyme and Novartis; and received research support from EMD Serono, Genzyme, and Roche. AL: Employee of Sanofi with ownership interest. JC: Employee of Sanofi with ownership interest. EP: Employee of Sanofi with ownership interest. AT: Personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Chugai, Roche, Novartis, Sanofi and Teva. Research support from Roche.
Study supported by Sanofi.