COPENHAGEN—Teriflunomide (14 mg and 7 mg) is safe and effective in the treatment of patients with clinically isolated syndrome, according to TOPIC trial data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
“These findings highlight the ability of early intervention with teriflunomide to delay onset of MS symptoms,” said Aaron E. Miller, MD, Professor of Neurology at the Icahn School of Medicine at Mount Sinai, New York, and his study collaborators. “To date, all teriflunomide phase III studies have shown consistent safety and efficacy, and greater efficacy for a 14-mg dose.”
Teriflunomide is a novel, once-daily, oral immunomodulator approved in the United States, Argentina, and Australia for the treatment of relapsing-remitting MS. Prior clinical studies of teriflunomide in patients with relapsing-remitting MS (TEMSO and TOWER) showed consistent efficacy across key clinical measures and a well-characterized safety profile. TOPIC was a phase III clinical trial conducted to assess the efficacy and safety of teriflunomide in patients with a first clinical episode suggestive of MS (clinically isolated syndrome).
In TOPIC, a double-blind, placebo-controlled, parallel-group study, 618 patients with clinically isolated syndrome were enrolled from February 2008 to September 2012 (projected end date, December 2012) and randomized to placebo, teriflunomide 7 mg, or teriflunomide 14 mg. TOPIC ended three months early as revised diagnostic criteria enabled earlier diagnosis of MS. The primary and key secondary end points were conversion to clinically definite MS and occurrence of a new clinical relapse or MRI lesion. Other efficacy end points and safety and tolerability were also assessed.
Baseline characteristics were generally well balanced among the treatment groups. Of the randomized population (n = 618), 59.1% had monofocal and 40.9% had multifocal lesion presentation, and 31.4% had one or more gadolinium-enhancing lesions. Median time since first neurologic event was two months.
Compared with placebo, teriflunomide 14 mg reduced the risk of conversion to clinically definite MS by 42.6%, with a probability of conversion to clinically definite MS at 108 weeks of 24.0% (probability for placebo group, 35.9%). Teriflunomide 14 mg also reduced the risk of occurrence of new relapse or new MRI lesion by 34.9%. As measured by MRI over the two-year study period, patients treated with teriflunomide 14 mg had a 5% increase in total lesion volume, compared with a 28% increase among patients treated with placebo. In addition, patients treated with teriflunomide 14 mg had a 59% reduction in gadolinium-enhancing T1 lesions, compared with patients receiving placebo.
Teriflunomide 7 mg reduced the risk of conversion to clinically definite MS by 37.2% (108-week probability, 27.6%) and the risk of occurrence of new relapse or new MRI lesion by 31.4%. The occurrence of adverse events was similar across treatment groups. The most common adverse events reported more frequently in the teriflunomide arms included alanine aminotransferase elevation, headache, hair thinning (14 mg only), diarrhea, and paresthesia.
—Glenn S. Williams
Vice President/Group Editor