Teriflunomide Demonstrates Significant Efficacy in Patients with Multiple Sclerosis

VBCN - May 2015 Volume 2, No 1 - Multiple Sclerosis
Chase Doyle

Washington, DC—In the treatment of patients with multiple sclerosis, a drug’s effect on time to first relapse is an important indicator of patient response to therapy. According to analyses presented at the 2015 annual meeting of the American Academy of Neurology, teriflunomide (Aubagio) significantly increased time to first relapse in 3 separate studies—TEMSO, TOWER, and TOPIC.

These trials are part of an ongoing teriflunomide clinical development program that has involved more than 5000 patients in 36 countries, and is among the largest of any multiple sclerosis research program. Some patients in the extension clinical trials have received teriflu­nomide for up to 10 years.

“The results from these 3 studies demonstrate the efficacy of teriflunomide on reducing relapses across a range of patients, including those with early MS [multiple sclerosis] and relapsing MS,” reported William D. Honeycutt, MD, Neurologist, Neurology Associates Clinical Research Unit, Maitland, FL. “Treatment with teriflunomide not only delayed the time to first relapse but was associated with a reduction in the risk of relapse as well.”

Teriflunomide is a once-daily oral immunomodulator approved for the treatment of patients with relapsing-remitting multiple sclerosis. Although the exact mechanism of action of teriflunomide is not fully understood, it may involve a reduction in the number of activated lymphocytes in the central nervous system.

TEMSO and TOWER Studies

TEMSO and TOWER were phase 3, placebo-controlled studies that were designed to assess the efficacy and safety of teriflunomide 14 mg and 7 mg in patients with relapsing forms of multiple sclerosis. TEMSO (N = 1086) and TOWER (N = 1165) enrolled patients with relapsing forms of multiple sclerosis, aged 18 to 55 years, with Expanded Disability Status Scale (EDSS) scores ≤5.5, and ≥1 relapses in the previous 12 months or ≥2 relapses in the previous 24 months.

TOPIC was a phase 3, placebo-controlled study of teriflunomide in 614 patients with a first clinical episode suggestive of multiple sclerosis. The study included patients aged 18 to 55 years with a first acute or subacute neurologic event consistent with demyelination (eg, optic neuritis, spinal cord syndrome, and brainstem and cerebellar syndromes) occurring within 90 days of randomization, and magnetic resonance imaging lesions characteristic of multiple sclerosis.

TEMSO was a 2-year clinical trial, and the treatment duration in the TOWER clinical trial was variable (ie, 48-152 weeks; treatment ended 48 weeks after the last patient was randomized). The treatment duration in the TOPIC clinical trial was ≤108 weeks.

In all 3 studies, a relapse was defined as the appearance of a new clinical symptom or a clinical worsening of a previous symptom that had been stable for at least 30 days. Relapses were confirmed when they were associated with a minimum increase in EDSS score and/or functional system score.


“Teriflunomide 14 mg consistently demonstrated a significant reduction in both annualized relapse rate and risk for disability progression confirmed for 12 weeks versus placebo,” Dr Honeycutt reported. “Teriflunomide 7 mg significantly reduced the annualized relapse rate, but not disability progression, in both studies [TEMSO and TOWER].”

Teriflunomide demonstrated similar efficacy in the TOPIC study. Flavia Nelson, MD, Neurologist, University of Texas Health Science Center, Houston, who presented a separate analysis, reported that “In TOPIC, teriflunomide 14 mg reduced the risk of relapse determining conversion to clinically definite MS by 42.6% compared with placebo (P = .008)….The 7-mg dose also showed statistically significant superiority to placebo on both end points, with a smaller effect.”

Demographic and baseline characteristics were broadly similar in the TEMSO and TOWER clinical trials, but patients in the TOPIC study were younger, had shorter time since their first neurologic event or symptom, and had lower baseline EDSS scores. The time since first symptom was longer for patients in the TEMSO clinical trial (8.7 years) than for patients in the TOWER clinical trial (8.0 years), Dr Honeycutt noted. In addition, more patients in the TEMSO study had secondary progressive or progressive-relapsing disease than did patients in the TOWER study.

Both doses of teriflunomide, 7 mg and 14 mg, showed similar safety profiles across all 3 studies. The most common treatment-emergent adverse events that were more frequent with teriflunomide than with placebo included headache, diarrhea, alanine aminotransferase increase, nausea, and hair thinning. A long-term safety analysis with teriflunomide revealed that the majority of the adverse events were mild to moderate, and the nature of these events was similar to that observed in the 3 placebo-
controlled studies.

“The findings from these 3 studies are clinically relevant, given the disruption to patients’ quality of life and increase in healthcare utilization associated with relapses,” Dr Honeycutt concluded. “The risk for relapse was significantly lower for patients who received teriflunomide than for those who received placebo.”

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