Ibudilast Slows Brain Atrophy Caused by Progressive Multiple Sclerosis

Although over a dozen therapies have been approved for the treatment of relapsing forms of multiple sclerosis, only 2 treatments—ocrelizumab and mitoxantrone—have been approved by the US Food and Drug Administration (FDA) for progressive multiple sclerosis.

Now, however, positive results from a recent phase 2 trial assessing the effectiveness of a new treatment, ibudilast, offers “a glimmer of hope” to patients who have this form of the disease, which is known to result in long-term disability, say investigators from the National Institute of Neurological Disorders and Stroke (NINDS).

For the phase 2 randomized trial, investigators enrolled patients between the ages of 21 and 65 who were diagnosed with progressive or secondary progressive multiple sclerosis from 28 US sites. The participants were randomly assigned (1:1) to receive either oral ibudilast—10 10 mg capsules daily—or matching placebo pills in 2 or 3 divided doses for the duration of 96 weeks.

Of the 255 participants who underwent randomization for the trial, 129 were assigned to receive ibudilast, while 126 where given placebo. Fifty-three percent of those receiving ibudilast had primary progressive disease along with 52% of those who received the placebo; the rest of the participants had secondary progressive disease.

For the initial 2-week period of the study, participants received 60 mg of ibudilast or matching placebo daily; after this period, the dose was increased to 100 mg of ibudilast or matching placebo. Dose adjustment for side effects was allowed at the investigator’s discretion up to week 8 of treatment, after which participants maintained their then-current daily dose of the trial regimen, study authors write.

Investigators conducted safety visits every 4 weeks through week 12 and then every 12 weeks through week 96. Every 6 months, the participants underwent MRI brain scans, where a variety of analysis techniques were used to determine differences in brain changes between the 2 treatment groups.

The investigators found that ibudilast slowed down the rate of brain atrophy compared with placebo. The estimated rate of change in the brain parenchymal fraction was -0.0010 per year with ibudilast (95% CI, -0.0025 to -0.0013); this was an absolute difference of 0.0009 per year (95% CI, 0.00004 to 0.0017; P=0.04), or around 2.5 milliliters less brain tissue lost with ibudilast compared with placebo over the 96 weeks of the study, a relative difference of 48%, the study authors write.

This means that although both treatment groups still experienced atrophy, the brains of the participants who received placebo shrunk about 2.5 milliliters more over 2 years compared with those who received ibudilast. However, is important to note that the investigators do not know whether this difference had any effect on symptoms or loss of function.

When it came to adverse events (AEs), there was no significant difference between the 2 treatment groups.

“Side effects of ibudilast included gastrointestinal symptoms, headache, and depression, with no increased rate of serious adverse events or infections,” Robert J. Fox, principal investigator from the Cleveland Clinic, said in a recent interview with our sister publication MD Magazine^®. “This combination of benefit on atrophy progression and safety profile points to a potential new therapy for progressive multiple sclerosis.”

Future research will test whether reducing brain atrophy impacts thinking, walking, and other issues experienced by those with the condition. Investigators also aim to determine if ibudilast can slow the progression of disability in these patients.