Evidence map›Paper›PMID 37460235›Full record

Trial reportNeurology2023

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

Henrik Ehrhardt, Jeffrey Lambe, Hussein Moussa, Eleni S Vasileiou, Grigorios Kalaitzidis, Olwen C Murphy, Angeliki G Filippatou, Nicole Pellegrini, Morgan Douglas, Simidele Davis and 11 more

Open access · greenAbstract readRandomized Controlled TrialMulticenter Study

PubMed Full text at PMC Publisher

In one paragraph

Trial report in Neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it

0cells of the map it votes in

9citing papers in PubMed

4.3field-weighted citation impact, top 6% of its field

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 17 citations in OpenAlex.

Optical coherence tomography in secondary progressive multiple sclerosis: cross-sectional and longitudinal exploratory analysis from the MS-SMART randomised controlled trial.Journal of neurology, neurosurgery, and psychiatry · 2025
Trial
Influence of OSCAR-IB criteria on test-retest reliability of Spectralis SD-OCT retinal thickness measurements in people with Multiple Sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
Article
Modulation of the immunological and neuroinflammatory microenvironment in older people with multiple sclerosis.Frontiers in immunology · 2026
Review
Application of optical coherence tomography in multiple sclerosis: consensus recommendations of the Austrian network (AN-OCT-MS).Journal of neurology · 2025
Article
Effect of Ibudilast vs Placebo on GFAP and Contactin levels in a phase 2 clinical trial in progressive multiple sclerosis.Neurology open access · 2025
Article
Primary Progressive Multiple Sclerosis-A Key to Understanding and Managing Disease Progression.International journal of molecular sciences · 2024
Review
Homonymous Hemiatrophy of Macular Ganglion Cell Layer as a Marker of Retrograde Neurodegeneration in Multiple Sclerosis-A Narrative Review.Diagnostics (Basel, Switzerland) · 2024
Review
Macular OCT's Proficiency in Identifying Retrochiasmal Visual Pathway Lesions in Multiple Sclerosis-A Pilot Study.Diagnostics (Basel, Switzerland) · 2024
Article
Diffusion tensor imaging in the SPRINT-MS clinical trial: Advancing trial methodology.Multiple sclerosis journal - experimental, translational and clinical
Article

4 · The record

Corrections and comments

Commented on by
Optical Coherence Tomography, Retinal Atrophy, and Neurodegeneration in Progressive Multiple Sclerosis: Sprinting to the Finish.2023

5 · Who and what money

Authors and funding

21 authors at 1 institution in 1 country.

Henrik EhrhardtFrom 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 LambeFrom 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 MoussaFrom 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 VasileiouFrom 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 KalaitzidisFrom 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 MurphyFrom 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 FilippatouFrom 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 PellegriniFrom 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 DouglasFrom 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 DavisFrom 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 NagyFrom 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 QuirogaFrom 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 HuFrom 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 LeeFrom 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 DuvalFrom 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 FitzgeraldFrom 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 PrinceFrom 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 CalabresiFrom 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 SotirchosFrom 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 BermelFrom 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 SaidhaFrom 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

Johns Hopkins University · US

Funding

Imaging Neurodegeneration in Multiple SclerosisR01NS082347 · NINDS · JOHNS HOPKINS UNIVERSITY · PI PETER A CALABRESI, Shiv Saidha · 2013 to 2026

$7.0M

OCT and OCTA image processing for retinal assessment of people with MSR01EY032284 · NEI · JOHNS HOPKINS UNIVERSITY · PI PRINCE, JERRY L · 2021 to 2024

$1.8M

NEI NIH HHS R01 EY032284NINDS NIH HHS R01 NS082347

6 · The paper itself

Abstract

BACKGROUND AND

objectivesGanglion 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.

methodsIn 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.

resultsOne 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.

Indexed as

Multiple SclerosisMultiple Sclerosis, Chronic ProgressiveRetinal DegenerationAtrophyHumansIndolizinesPyrazolesPyridinesRetinaTomography, Optical CoherenceibudilastIndolizinesPyrazolesPyridines

Identifiers

PMID37460235

DOI10.1212/WNL.0000000000207551

PMCPMC10491449

OpenAlexW4384498391

What Socratic holds

Textmetadata

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.