BACKGROUND: Ibudilast is a phosphodiesterase inhibitor influencing inflammation 
and neurodegeneration in multiple sclerosis (MS). This study evaluated the 
safety, tolerability, and effects on MRI parameters of 2 different doses of 
ibudilast in relapsing forms of MS.
METHODS: In this multicenter, double-blind, phase 2 trial, patients with 
relapsing MS and gadolinium-enhancing lesions were randomly assigned 1:1:1 to 
receive 30 or 60 mg ibudilast or placebo every day for 12 months. The primary 
endpoint was the cumulative number of newly active lesions on bimonthly brain 
MRI over 12 months. Secondary endpoints included relapse rate, change in 
Expanded Disability Status Scale (EDSS) score, T2-hyperintense and 
T1-hypointense lesion volumes, and percent brain volume change (PBVC).
RESULTS: A total of 297 patients were randomized in 19 centers. During the first 
12 months, the mean number of active lesions and relapse rate did not differ 
between treatment arms. A reduction in PBVC (p = 0.04) was found in the 60-mg 
group (0.8%) compared with placebo (1.2%). Post hoc analysis showed a reduction 
in the proportion active lesions that evolved into persistent black holes for 
the 60-mg (0.14; p = 0.004) and 30-mg (0.17; p = 0.036) groups compared with the 
placebo group (0.24). Over 2 years, there were fewer patients (p = 0.026) with 
confirmed progression on the EDSS. Treatment with ibudilast was generally safe 
and well tolerated.
CONCLUSION: Ibudilast showed no beneficial effect on the rate of newly active 
lesions and relapses. However, preliminary evidence suggests that ibudilast 
seems to act in a neuroprotective fashion as measured by 2 independent MRI 
outcomes, with a possible beneficial clinical effect on disability progression.
CLASSIFICATION OF EVIDENCE: This interventional study provides Class III 
evidence on the effect of ibudilast on disease activity.