Teriflunomide Reduces Cortical Gray Matter Volume Loss

OCTOBER 28, 2017
Matt Hoffman
Dr Robert ZivadinovRobert Zivadinov, MD
Results of the TOPIC study revealed that once-daily 14 mg teriflunomide demonstrated a statistically significant impact on reducing cortical gray matter volume (CGMV) loss in patients with clinically definitive multiple sclerosis (CDMS). 

Additionally, the data showed a significant association of early CGMV loss with long-term CDMS conversion, which suggests that the loss of CGMV earlier in MS can predict longer-term CDMS conversion. The TOPIC study was presented as a poster at MS Paris 2017, the 7th annual joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

“When you look at people as a group, whether they have been treated or not, and look at the conversion to CDMS, there was a very high association between people who develop CGM atrophy and converted during the 2 years of the trial, or in the 2 years after, to CDMS.” Robert Zivadinov, MD, a professor of neurology at the University of Buffalo and lead investigator, told MD Magazine. “Cortical disease is present in these patients from the first clinical attack, and accelerates very much in the 2, 3, or 4 years of the disease, [which helps] to predict conversion to CDMS.” 

In the trial, 614 patients were randomized 1:1:1 to teriflumonide 7 mg (n = 203), teriflumonide 14 mg (n = 214), or placebo (n = 197), with the option to enter an extension of their original dose upon completion of the original 108-week study.

Average patient age was 32 for placebo, 31.5 for teriflunomide 7 mg, and 32.7 for teriflunomide 14 mg, with an average of 1.8 months since their first symptom of MS. 

Over the course of the 2 years, patients were given MRI to measure CGMV at month 6, month 12, month 18, and month 24. At all time points, teriflunomide 14 gm reduced CGMV loss, while teriflunomide 7 gm reduced CGMV loss at months 18 and 24. At month 6, CGMV increased 0.07 from baseline, while CGMV loss was reduced 0.32 from baseline at month 12, 0.45 at month 18, and 0.84 at month 24.

Reduction of CDMS conversion risk was also observed at months 12, 18, and 24 with teriflunomide 14 mg. The risk was reduced by 46.3% at month 12 (P =.0220), 42.1% at month 18 (P =.0260), and 46.6% at month 24 (P =.0085).  

“We found very, very strong data that both doses of [teriflumonide] slowed down CGM atrophy compared to placebo, starting at month 6 and continued at months 12, 18, and 24,” Zivadinov said. “We also found that when we divided these 3 groups, there was a proportion of patients who developed less cortical atrophy with [teriflumonide] compared to placebo, and on the other hand, there were many more placebo patients who developed more cortical atrophy.”

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