P044 - Long-term clinical and magnetic resonance imaging outcomes from patients treated with teriflunomide: Results from a phase 2 extension study

Abstract

Background/objectives Teriflunomide is a once-daily oral immunomodulator for the treatment of relapsing-remitting multiple sclerosis. The clinical development program for teriflunomide demonstrated consistent efficacy and a well-characterized, manageable safety and tolerability profile. Here we report efficacy outcomes from patients treated long-term with teriflunomide in a phase 2 study (nct01487096) and its extension (nct00228163). Design and methods Patients with relapsing multiple sclerosis were randomized 1:1:1 to teriflunomide 14 mg or 7 mg, or placebo. Of 160 patients completing the 36-week core study, 147 entered the long-term extension. Teriflunomide-treated patients continued on their original dose; placebo-treated patients were rerandomized 1:1 to teriflunomide, 14 mg or 7 mg. Expanded disability status scale score was assessed every 24 weeks, magnetic resonance imaging was performed every 48 weeks until week 480, and clinical relapses were reported throughout the study. Results At june 28, 2013, cumulative duration of teriflunomide exposure, including both dose groups, was >990 patient-years: 63 patients remained on study. Increases in mean expanded disability status scale score following up to 528 weeks of treatment were minimal. Annualized relapse rates were low: 0.190 (14-mg group) and 0.254 (7-mg group). In both dose groups, mean numbers of gadolinium-enhancing t1 lesions and newly active t2 lesions were lower at week 480 vs. core study end. Compared with the 7-mg group, the teriflunomide 14-mg group had less of an increase from baseline in t2 lesion volume and less decline from baseline in cerebral volume at week 432. There were no new or unexpected safety signals with continued teriflunomide exposure. Conclusions Clinical and radiological signs of disease remained low in patients receiving teriflunomide for up to 12 years in a phase 2 study and its extension. These data are consistent with sustained efficacy of long-term teriflunomide treatment in patients with multiple sclerosis. Teriflunomide is a once-daily oral immunomodulator for the treatment of relapsing-remitting multiple sclerosis. The clinical development program for teriflunomide demonstrated consistent efficacy and a well-characterized, manageable safety and tolerability profile. Here we report efficacy outcomes from patients treated long-term with teriflunomide in a phase 2 study (nct01487096) and its extension (nct00228163). Patients with relapsing multiple sclerosis were randomized 1:1:1 to teriflunomide 14 mg or 7 mg, or placebo. Of 160 patients completing the 36-week core study, 147 entered the long-term extension. Teriflunomide-treated patients continued on their original dose; placebo-treated patients were rerandomized 1:1 to teriflunomide, 14 mg or 7 mg. Expanded disability status scale score was assessed every 24 weeks, magnetic resonance imaging was performed every 48 weeks until week 480, and clinical relapses were reported throughout the study. At june 28, 2013, cumulative duration of teriflunomide exposure, including both dose groups, was >990 patient-years: 63 patients remained on study. Increases in mean expanded disability status scale score following up to 528 weeks of treatment were minimal. Annualized relapse rates were low: 0.190 (14-mg group) and 0.254 (7-mg group). In both dose groups, mean numbers of gadolinium-enhancing t1 lesions and newly active t2 lesions were lower at week 480 vs. core study end. Compared with the 7-mg group, the teriflunomide 14-mg group had less of an increase from baseline in t2 lesion volume and less decline from baseline in cerebral volume at week 432. There were no new or unexpected safety signals with continued teriflunomide exposure. Clinical and radiological signs of disease remained low in patients receiving teriflunomide for up to 12 years in a phase 2 study and its extension. These data are consistent with sustained efficacy of long-term teriflunomide treatment in patients with multiple sclerosis.