Effects of Ibudilast on Retinal Atrophy in Progressive Multiple Sclerosis Subtypes: Post Hoc Analyses of the SPRINT-MS Trial.

Humans Multiple Sclerosis / complications Multiple Sclerosis, Chronic Progressive / diagnostic imaging Retina / pathology Retinal Degeneration / diagnostic imaging Pyridines / therapeutic use Tomography, Optical Coherence / methods Atrophy / drug therapy

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
05 09 2023
Historique:
received: 09 06 2022
accepted: 08 05 2023
pmc-release: 05 09 2024
medline: 6 9 2023
pubmed: 18 7 2023
entrez: 17 7 2023
Statut: ppublish

Résumé

Ganglion cell + inner plexiform layer (GCIPL) thinning, measured by optical coherence tomography (OCT), reflects global neurodegeneration in multiple sclerosis (MS). Atrophy of the inner (INL) and outer nuclear layer (ONL) may also be prominent in progressive MS (PMS). The phase 2, SPRINT-MS trial found reduced brain atrophy with ibudilast therapy in PMS. In this post hoc analysis of the SPRINT-MS trial, we investigate (1) retinal atrophy (2) differences in response by subtype and (3) associations between OCT and MRI measures of neurodegeneration. In the multicenter, double-blind SPRINT-MS trial, participants with secondary progressive MS (SPMS) or primary progressive MS (PPMS) were randomized to ibudilast or placebo. OCT and MRI data were collected every 24 weeks for 96 weeks. Extensive OCT quality control and algorithmic segmentation produced consistent results across Cirrus HD-OCT and Spectralis devices. Primary endpoints were GCIPL, INL, and ONL atrophy, assessed by linear mixed-effects regression. Secondary endpoints were associations of OCT measures, brain parenchymal fraction, and cortical thickness, assessed by partial Pearson correlations. One hundred thirty-four PPMS and 121 SPMS participants were included. GCIPL atrophy was 79% slower in the ibudilast (-0.07 ± 0.23 µm/y) vs placebo group (-0.32 ± 0.20 µm/y, Ibudilast treatment decreased GCIPL atrophy in PMS, driven by the PPMS cohort, with no effect seen in SPMS. Modulated atrophy of retinal layers may be detectable in sample sizes smaller than the SPRINT-MS trial and correlate with whole brain atrophy in PMS, further highlighting their utility as outcomes in PMS. This study provides Class II evidence that ibudilast reduces composite ganglion cell + inner plexiform layer atrophy, without reduction of inner or outer nuclear layer atrophy, in patients with primary progressive MS but not those with secondary progressive MS.

Sections du résumé

BACKGROUND AND OBJECTIVES
Ganglion cell + inner plexiform layer (GCIPL) thinning, measured by optical coherence tomography (OCT), reflects global neurodegeneration in multiple sclerosis (MS). Atrophy of the inner (INL) and outer nuclear layer (ONL) may also be prominent in progressive MS (PMS). The phase 2, SPRINT-MS trial found reduced brain atrophy with ibudilast therapy in PMS. In this post hoc analysis of the SPRINT-MS trial, we investigate (1) retinal atrophy (2) differences in response by subtype and (3) associations between OCT and MRI measures of neurodegeneration.
METHODS
In the multicenter, double-blind SPRINT-MS trial, participants with secondary progressive MS (SPMS) or primary progressive MS (PPMS) were randomized to ibudilast or placebo. OCT and MRI data were collected every 24 weeks for 96 weeks. Extensive OCT quality control and algorithmic segmentation produced consistent results across Cirrus HD-OCT and Spectralis devices. Primary endpoints were GCIPL, INL, and ONL atrophy, assessed by linear mixed-effects regression. Secondary endpoints were associations of OCT measures, brain parenchymal fraction, and cortical thickness, assessed by partial Pearson correlations.
RESULTS
One hundred thirty-four PPMS and 121 SPMS participants were included. GCIPL atrophy was 79% slower in the ibudilast (-0.07 ± 0.23 µm/y) vs placebo group (-0.32 ± 0.20 µm/y,
DISCUSSION
Ibudilast treatment decreased GCIPL atrophy in PMS, driven by the PPMS cohort, with no effect seen in SPMS. Modulated atrophy of retinal layers may be detectable in sample sizes smaller than the SPRINT-MS trial and correlate with whole brain atrophy in PMS, further highlighting their utility as outcomes in PMS.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that ibudilast reduces composite ganglion cell + inner plexiform layer atrophy, without reduction of inner or outer nuclear layer atrophy, in patients with primary progressive MS but not those with secondary progressive MS.

Identifiants

DOI: 10.1212/WNL.0000000000207551 PMID: 37460235 PMC: PMC10491449
pubmed: 37460235
pii: WNL.0000000000207551
doi: 10.1212/WNL.0000000000207551
pmc: PMC10491449
doi:

Substances chimiques

ibudilast M0TTH61XC5
Pyridines 0

Types de publication

Randomized Controlled Trial Multicenter Study Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1014-e1024

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS082347
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2023 American Academy of Neurology.

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Auteurs

Henrik Ehrhardt (H)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.
ORCID: 0000-0003-3246-6609

Jeffrey Lambe (J)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Hussein Moussa (H)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Eleni S Vasileiou (ES)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.
ORCID: 0000-0002-8639-8405

Grigorios Kalaitzidis (G)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Olwen C Murphy (OC)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.
ORCID: 0000-0001-7880-8948

Angeliki G Filippatou (AG)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.
ORCID: 0000-0003-0419-233X

Nicole Pellegrini (N)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Morgan Douglas (M)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.
ORCID: 0000-0003-0749-7606

Simidele Davis (S)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Natalia Nagy (N)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Agustina Quiroga (A)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Chen Hu (C)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Alexandra Zambriczki Lee (A)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Anna Duval (A)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Kathryn C Fitzgerald (KC)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.
ORCID: 0000-0003-3137-0322

Jerry L Prince (JL)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Peter A Calabresi (PA)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.
ORCID: 0000-0002-7776-6472

Elias S Sotirchos (ES)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.
ORCID: 0000-0002-8812-1637

Robert Bermel (R)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH.

Shiv Saidha (S)

From the Department of Neurology (H.E., J.L., H.M., E.S.V., G.K., O.C.M., A.G.F., N.P., M.D., S.D., N.N., A.Q., C.H., A.Z.L., A.D., K.C.F., P.A.C., E.S.S., S.S.), Johns Hopkins University School of Medicine; Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD; and Mellen Center for Multiple Sclerosis (R.B.), Cleveland Clinic, OH. ssaidha2@jhmi.edu.
ORCID: 0000-0001-6387-0714

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Effects of Ibudilast on Retinal Atrophy in...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Effects of Ibudilast on Retinal Atrophy in...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Sclérose en plaques chronique progressive › Effects of Ibudilast on Retinal Atrophy in...
questionsmedicales.fr › Organes des sens › Oeil › Rétine › Effects of Ibudilast on Retinal Atrophy in...
questionsmedicales.fr › Maladies de l'oeil › Rétinopathies › Dégénérescence de la rétine › Effects of Ibudilast on Retinal Atrophy in...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Effects of Ibudilast on Retinal Atrophy in...
questionsmedicales.fr › Techniques d'investigation › Imagerie optique › Tomographie optique › Tomographie par cohérence optique › Effects of Ibudilast on Retinal Atrophy in...
questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Atrophie › Effects of Ibudilast on Retinal Atrophy in...