Response to ibudilast treatment according to progressive multiple sclerosis disease phenotype.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
14
04
2020
revised:
12
10
2020
accepted:
20
10
2020
pubmed:
19
1
2021
medline:
9
10
2021
entrez:
18
1
2021
Statut:
ppublish
Résumé
Determine whether a treatment effect of ibudilast on brain atrophy rate differs between participants with primary (PPMS) and secondary (SPMS) progressive multiple sclerosis. Progressive forms of MS are both associated with continuous disability progression. Whether PPMS and SPMS differ in treatment response remains unknown. SPRINT-MS was a randomized, placebo-controlled 96-week phase 2 trial in both PPMS (n = 134) and SPMS (n = 121) patients. The effect of PPMS and SPMS phenotype on the rate of change of brain atrophy measured by brain parenchymal fraction (BPF) was examined by fitting a three-way interaction linear-mixed model. Adjustment for differences in baseline demographics, disease measures, and brain size was explored. Analysis showed that there was a three-way interaction between the time, treatment effect, and disease phenotype (P < 0.06). After further inspection, the overall treatment effect was primarily driven by patients with PPMS (P < 0.01), and not by patients with SPMS (P = 0.97). This difference may have been due to faster brain atrophy progression seen in the PPMS placebo group compared to SPMS placebo (P < 0.02). Although backward selection (P < 0.05) retained age, T2 lesion volume, RNFL, and longitudinal diffusivity as significant baseline covariates in the linear-mixed model, the adjusted overall treatment effect was still driven by PPMS (P < 0.01). The previously reported overall treatment effect of ibudilast on worsening of brain atrophy in progressive MS appears to be driven by patients with PPMS that may be, in part, because of the faster atrophy progression rates seen in the placebo-treated group.
Sections du résumé
OBJECTIVE
Determine whether a treatment effect of ibudilast on brain atrophy rate differs between participants with primary (PPMS) and secondary (SPMS) progressive multiple sclerosis.
BACKGROUND
Progressive forms of MS are both associated with continuous disability progression. Whether PPMS and SPMS differ in treatment response remains unknown.
DESIGN/METHODS
SPRINT-MS was a randomized, placebo-controlled 96-week phase 2 trial in both PPMS (n = 134) and SPMS (n = 121) patients. The effect of PPMS and SPMS phenotype on the rate of change of brain atrophy measured by brain parenchymal fraction (BPF) was examined by fitting a three-way interaction linear-mixed model. Adjustment for differences in baseline demographics, disease measures, and brain size was explored.
RESULTS
Analysis showed that there was a three-way interaction between the time, treatment effect, and disease phenotype (P < 0.06). After further inspection, the overall treatment effect was primarily driven by patients with PPMS (P < 0.01), and not by patients with SPMS (P = 0.97). This difference may have been due to faster brain atrophy progression seen in the PPMS placebo group compared to SPMS placebo (P < 0.02). Although backward selection (P < 0.05) retained age, T2 lesion volume, RNFL, and longitudinal diffusivity as significant baseline covariates in the linear-mixed model, the adjusted overall treatment effect was still driven by PPMS (P < 0.01).
INTERPRETATION
The previously reported overall treatment effect of ibudilast on worsening of brain atrophy in progressive MS appears to be driven by patients with PPMS that may be, in part, because of the faster atrophy progression rates seen in the placebo-treated group.
Identifiants
pubmed: 33460301
doi: 10.1002/acn3.51251
pmc: PMC7818089
doi:
Substances chimiques
Phosphodiesterase Inhibitors
0
Pyridines
0
ibudilast
M0TTH61XC5
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
111-118Subventions
Organisme : NINDS NIH HHS
ID : U01 NS077179
Pays : United States
Organisme : NINDS NIH HHS
ID : U24 NS107156
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS077352
Pays : United States
Organisme : NINDS NIH HHS
ID : U24 NS107182
Pays : United States
Organisme : National Institute of Neurological Disorders and Stroke (NINDS)
ID : U01NS082329
Pays : International
Organisme : NINDS NIH HHS
ID : U24 NS107205
Pays : United States
Informations de copyright
© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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