Estriol Added to Glatiramer Acetate Improves Cognition, Reduces Relapse Rate in MS

VBCN - July 2014 Volume 1, No 2

Philadelphia, PA—Estriol may represent a future novel treatment option for patients with relapsing-remitting multiple sclerosis (RRMS). In a phase 2 randomized, double-blind, placebo-­controlled trial of women with RRMS, estriol, given with glatiramer acetate, reduced the relapse rate by almost 50% with only 1 year of treatment and improved cognition, reported Rhonda Voskuhl, MD, Director of the MS program, University of California, Los Angeles, at the 2014 meeting of the American Academy of Neurology.

Because MS relapses are decreased by approximately 80% during late pregnancy, the investigators tested the effect of estriol (an estrogen unique to pregnancy) in women aged 18 to 50 years with RRMS. Estrogen treatment has been shown to ameliorate MS and improve cognition in animal studies.

“It makes a lot of sense to have something circulating in the mother’s blood that would be neuroprotective, to protect the fetal developing nervous system,” Dr Voskuhl said.

In this 16-center study, 158 women with RRMS receiving glatiramer acetate were randomized to oral estriol, 8 mg daily, plus standard MS treatment, or to placebo plus standard MS treatment.

The mean disease duration of participants was 3 years, and 99% of patients had at least 1 relapse in the preceding 24 months; of these, 29.4% had at least 1 enhancing lesion on a single screening magnetic resonance imaging. The mean Expanded Disability Status Scale (EDSS) score was 2.2.

The mean estriol levels at baseline were not different between the 2 groups, but they were significantly higher in the estriol group at months 3 to 24. After 12 months, the relapse rate (confirmed change in the EDSS by the examining neurologist) was 47% lower in the estriol group compared with placebo (P = .030 when adjusted for baseline characteristics). At 24 months, the relapse rate remained lower by 32% in the women assigned to estriol, but it was no longer significant (P = .152).

An improvement in cognitive test scores was also observed in the estriol group. The improvement from baseline on the 3-minute Paced Auditory Serial Addition Test (PASAT)3 and PASAT2 was significantly better in the estriol group at 12 months. “It was about a 5.5% to 6% change, which amounts to about a 3-point change in the PASAT,” Dr Voskuhl said.

The superiority of estriol at 12 months on the PASAT3 and PASAT2 scores was also significant in patients with a baseline PASAT3 score of <55 at baseline. “Clearly, the effect is driven in these people who are doing more poorly on the PASAT,” she said. “They were getting improvements of 12%, which is about a 6- to 7-point increase on the PASAT.”

In the second year, PASAT scores in the placebo group began to catch up with the estriol group, which reflects the effect of glatiramer acetate on cognition in year 2, said Dr Voskuhl. There was no effect of estriol on the EDSS.

There were no gynecologic safety signals in the women taking estriol, she noted. The rates of uterine fibroids, uterine endometrial hypertrophy, abnormal uterine proliferation, and fibrocystic breast disease were not different between the 2 groups.

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