Journal article
Response to ibudilast treatment according to progressive multiple sclerosis disease phenotype
Annals of clinical and translational neurology, Vol.8(1), pp.111-118
01/2021
DOI: 10.1002/acn3.51251
PMCID: PMC7818089
PMID: 33460301
Abstract
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.
Details
- Title: Subtitle
- Response to ibudilast treatment according to progressive multiple sclerosis disease phenotype
- Creators
- Andrew D Goodman - Department of Neurology, University of Rochester, Rochester, New York, USAJanel K Fedler - University of Iowa, Iowa City, Iowa, USAJon Yankey - University of Iowa, Iowa City, Iowa, USAElizabeth A Klingner - University of Iowa, Iowa City, Iowa, USADixie J Ecklund - University of Iowa, Iowa City, Iowa, USAChristopher V Goebel - Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, Ohio, USARobert A Bermel - Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, Ohio, USAMarianne Chase - Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USAChristopher S Coffey - University of Iowa, Iowa City, Iowa, USAEric C Klawiter - Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USARobert T Naismith - Department of Neurology, Washington University, St Louis, Missouri, USARobert J Fox - Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, Ohio, USASPRINT-MS Investigators
- Resource Type
- Journal article
- Publication Details
- Annals of clinical and translational neurology, Vol.8(1), pp.111-118
- DOI
- 10.1002/acn3.51251
- PMID
- 33460301
- PMCID
- PMC7818089
- NLM abbreviation
- Ann Clin Transl Neurol
- ISSN
- 2328-9503
- eISSN
- 2328-9503
- Grant note
- U24 NS107156 / NINDS NIH HHS U01NS082329 / National Institute of Neurological Disorders and Stroke (NINDS) U01 NS077352 / NINDS NIH HHS U24 NS107182 / NINDS NIH HHS U01 NS077179 / NINDS NIH HHS U24 NS107205 / NINDS NIH HHS
- Language
- English
- Date published
- 01/2021
- Academic Unit
- Biostatistics
- Record Identifier
- 9984214784802771
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