Serum macrophage migration inhibitory factor levels predict brain atrophy in people with primary progressive multiple sclerosis.

BACKGROUND

Macrophage migration inhibitory factor (MIF) is a cytokine linked to multiple sclerosis (MS) progression that is thought to be inhibited by ibudilast. SPRINT-MS was a phase 2 placebo-controlled trial of ibudilast in progressive multiple sclerosis (PMS).

OBJECTIVE

To determine whether baseline MIF levels predict imaging outcomes and assess the effects of ibudilast on serum and cerebrospinal fluid (CSF) MIF levels in people with PMS treated with ibudilast.

METHODS

Participants in the SPRINT-MS trial were treated with either ibudilast or placebo and underwent brain magnetic resonance imaging (MRI) every 24 weeks over a duration of 96 weeks. MIF was measured in serum and CSF.

RESULTS

MIF levels were compared with imaging outcomes in 223 participants from the SPRINT-MS study. In the primary progressive multiple sclerosis (PPMS) cohort, males had higher serum (

CONCLUSIONS

Serum MIF levels were associated with male sex and predicted brain atrophy in PPMS, but not SPMS. Ibudilast did not demonstrate an effect on MIF levels, as compared with placebo, although we cannot exclude a functional effect.

Déclaration de conflit d'intérêts

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.C.L., S.C.D.-P., M.J.A., M.D.S., J.W.M., and S.P.G. declared no potential conflicts of interest. M.I.R.-M. has received consulting fees from Novartis. P.B. has received grant funding to JHU from Amylyx pharmaceuticals, Genentech, EMD-Serono, and GSK. R.J.F received personal consulting fees from AB Science, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Immunic, INmune Bio, Janssen, Lily, Novartis, Sanofi, Siemens, and TG Therapeutics; served on advisory committees for AB Science, Biogen, Immunic, Janssen, Novartis, and Sanofi; and received clinical trial contract and research grant funding from Biogen, Novartis, and Sanofi. S.S. has received consulting fees from Medical Logix for the development of CME programs in neurology and has served on scientific advisory boards for Biogen, Novartis, Genentech Corporation, TG therapeutics, Clene Pharmaceuticals, and ReWind therapeutics. He has performed consulting for Novartis, Genentech Corporation, JuneBrain LLC, Innocare Pharma, Kiniksa pharmaceuticals, and Lapix therapeutics. He is the PI of investigator-initiated studies funded by Genentech Corporation, Biogen, and Novartis. He previously received support from the Race to Erase MS foundation. He has received equity compensation for consulting from JuneBrain LLC and Lapix therapeutics. He was also the site investigator of trials sponsored by MedDay Pharmaceuticals and Clene Pharmaceuticals, and is the site investigator of trials sponsored by Novartis, as well as Lapix therapeutics. P.A.C. received funding from MRF for this work and is PI on a grant from Genentech to JHU. He has received consulting fees from Lilly, Idorsia, and Novartis.