title: Ibudilast in relapsing-remitting multiple sclerosis: a neuroprotectant?
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  METHODS
  This interventional study provides Class III evidence on the effect of ibudilast on disease activity.
authors.affiliation: Department of Radiology, VU University Medical Center, MB, Amsterdam, The Netherlands. f.barkhof@vumc.nl
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: H E
authors.initials: HE
authors.lastname: Hulst
authors.forename: J
authors.initials: J
authors.lastname: Drulovic
authors.forename: B M J
authors.initials: BM
authors.lastname: Uitdehaag
authors.forename: K
authors.initials: K
authors.lastname: Matsuda
authors.forename: R
authors.initials: R
authors.lastname: Landin
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009929:Organ Size; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome; D007212:Indolizines; D011720:Pyrazoles
chemical_list: D018696:Neuroprotective Agents; D011725:Pyridines; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles