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.
RCT Entities:
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.
Authors: Frederik Barkhof; Jack H Simon; Franz Fazekas; Marco Rovaris; Ludwig Kappos; Nicola de Stefano; Chris H Polman; John Petkau; Ernst W Radue; Maria P Sormani; David K Li; Paul O'Connor; Xavier Montalban; David H Miller; Massimo Filippi Journal: Nat Rev Neurol Date: 2011-12-06 Impact factor: 42.937
Authors: Ziva D Cooper; Kirk W Johnson; Martina Pavlicova; Andrew Glass; Suzanne K Vosburg; Maria A Sullivan; Jeanne M Manubay; Diana M Martinez; Jermaine D Jones; Phillip A Saccone; Sandra D Comer Journal: Addict Biol Date: 2015-05-14 Impact factor: 4.280
Authors: Olaf Stüve; Bernd C Kieseier; Bernhard Hemmer; Hans-Peter Hartung; Amer Awad; Elliot M Frohman; Benjamin M Greenberg; Michael K Racke; Scott S Zamvil; J Theodore Phillips; Ralf Gold; Andrew Chan; Uwe Zettl; Ron Milo; Ellen Marder; Omar Khan; Todd N Eagar Journal: Arch Neurol Date: 2010-07-12
Authors: Xiaopeng Zhou; Ken E Sakaie; Josef P Debbins; John E Kirsch; Curtis Tatsuoka; Robert J Fox; Mark J Lowe Journal: Magn Reson Imaging Date: 2016-08-30 Impact factor: 2.546
Authors: Robert J Fox; Christopher S Coffey; Merit E Cudkowicz; Trevis Gleason; Andrew Goodman; Eric C Klawiter; Kazuko Matsuda; Michelle McGovern; Robin Conwit; Robert Naismith; Akshata Ashokkumar; Robert Bermel; Dixie Ecklund; Maxine Koepp; Jeffrey Long; Sneha Natarajan; Srividya Ramachandran; Thomai Skaramagas; Brenda Thornell; Jon Yankey; Mark Agius; Khurram Bashir; Bruce Cohen; Patricia Coyle; Silvia Delgado; Dana Dewitt; Angela Flores; Barbara Giesser; Myla Goldman; Burk Jubelt; Neil Lava; Sharon Lynch; Augusto Miravalle; Harold Moses; Daniel Ontaneda; Jai Perumal; Michael Racke; Pavle Repovic; Claire Riley; Christopher Severson; Shlomo Shinnar; Valerie Suski; Bianca Weinstock-Gutman; Vijayshree Yadav; Aram Zabeti Journal: Contemp Clin Trials Date: 2016-08-10 Impact factor: 2.226