Similar Effects Seen for Fingolimod, Placebo in Primary Progressive Multiple Sclerosis

In patients with primary progressive multiple sclerosis (PPMS), fingolimod resulted in similar mean percent brain volume change (PBVC) and percent change in spinal cord area (PCSCA) vs. placebo, according to data from the INFORMS study.

“Anti-inflammatory strategies currently successfully applied in RRMS cannot be automatically translated into the PPMS population,” Özgür Yaldizli, MD, study investigator and neurologist from the UCL Institute of Neurology, Queen Square Multiple Sclerosis Centre, London, told Neurology Advisor. “We need novel approaches to treat people with PPMS.”

Yaldizli presented the results at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress in Barcelona.

The catalyst for the analysis, Dr. Yaldizli said, was that in the past decade, studies have consistently shown that brain and spinal cord atrophy are more closely related to clinical disease progression in MS than magnetic resonance imaging (MRI) markers of inflammation. This led Dr. Yaldizli and colleagues to enroll 823 patients (48.4% women; mean age, 48.5 ± 8.4 years) and follow them for three years. Patients were included if they had a clinical diagnosis of PPMS; disease duration of two to 10 years; and objective evidence of disability progression in the previous two years.

From baseline to last MRI, mean PBVC was comparable for fingolimod (‒1.34 ± 1.22) compared with placebo (‒1.42 ± 1.27; P=.707), despite low inflammatory activity at baseline. This corresponded with a PCSCA of ‒2.44 ± 6.06 in the fingolimod arm and ‒2.04 ± 5.92 in the placebo arm (P=.263). During months 0 to 24, PBVC and PCSCA were generally linear, with a lower rate of decrease afterwards.

When researchers extended the analysis from 0 to 36 months, they found a significant association between measures of tissue loss and disability progression, including between PBVC and progression of Expanded Disability Status Scale (P=.0007), timed 25-foot walk test  (P=.004), and nine-hole peg test (P<.0004).

“Although the PPMS patients included in the INFORMS trial had a relatively low level of MRI-detected inflammation, the effect of fingolimod on MRI-markers of inflammation was consistent with that observed in RRMS patients,” Dr. Yaldizli said. “However, disappointingly, in INFORMS, there was neither a significant treatment effect on disease progression nor on brain or cervical spinal cord atrophy.”

For future one-year trials in PPMS, Dr. Yaldizli and colleagues estimate that a sample size of 140 patients per arm will be necessary to detect a treatment difference in PBVC of 40% with 80% power, based on the mean and standard deviation found at one year with placebo.

For more coverage of ECTRIMS 2015, go here.

Reference

1. Yaldizli Ö et al. Abstract 110. Presented at: The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress; Oct. 7-10, 2015; Barcelona.