メディシンバ応援の掲示板
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22273
>>22195
以前紹介した発表の内容が記事になってますね。
結果は良好とのこと。
Ibudilast has a significant beneficial effect on slowly evolving lesions (SELs) in patients with progressive multiple sclerosis (MS), new data suggest.
Through its effect on SELs, "we have a suspicion that ibudilast may be exerting some of its protective effect by abrogating chronic active lesions," study investigator Daniel Ontaneda, MD, Mellen Center for Multiple Sclerosis at Cleveland Clinic, in Ohio, told Medscape Medical News.
The findings were presented at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2022.
First-in-Class Agent
Chronic active lesions (CALs) contribute to clinical worsening among patients with MS. SELs have been proposed as a biomarker for CALs and have been associated with worsening disability.
Ibudilast is an investigational, first-in-class, orally bioavailable small-molecule phosphodiesterase-4 and -10 inhibitor and macrophage migration inhibitory factor inhibitor.
As previously reported by Medscape Medical News, the drug has shown promise as a treatment for progressive MS in the phase 2 multicenter SPRINT-MS trial.
In the new analysis, Ontaneda and colleagues assessed the effect of ibudilast on SELs on MRI scans using data from 195 SPRINT-MS participants with primary or secondary progressive MS. Ninety-seven patients received oral ibudilast (up to 100 mg/d), and 98 received matching placebo.
At baseline, the mean SEL volumes were 1.08 mL in the ibudilast group and 1.49 mL in the placebo group.
Overall, treatment with ibudilast was associated with a significant 26% decrease in SEL volume (P = .004). There was some evidence that the impact was greater for patients with primary progressive MS.
Collectively, the data continue to suggest a beneficial effect of ibudilast in MS, the researchers report.
"Tantalizing" New Data
Reached for comment, Shiv Saidha, MBBCh, MD, professor of neurology, Division of Neuroimmunology and Neurological Infections, Johns Hopkins Hospital and Johns Hopkins University School of Medicine, Baltimore, Maryland, said ibudilast is a "promising therapy with a novel mechanism of action thought to reduce activation of microglia.
"It's hypothesized that the enlargement of these slowly evolving lesions, which correlate with disability accumulation, might be related to ongoing microglial inflammation and this drug might reduce that, which is tantalizing," Saidha, who was not involved in the study, told Medscape Medical News.
Saidha said it's also "fascinating" that ibudilast seems to consistently have a greater impact in primary progressive MS than secondary progressive MS.
"It raises all sorts of questions about the pathobiological underpinnings of these two subtypes of the disease that many of us conventionally think of as being very similar to one another pathobiologically.
"But maybe either they're pathobiologically not as similar as we think, or in order for the for these drugs to be beneficial in secondary progressive MS, they need to be given much earlier," Saidha commented.
pac*****
参考
P188 Effect of ibudilast on slowly-evolving lesions in progressive multiple sclerosis
Kunio Nakamura (United States)
K. Nakamura1, J. Bena2, R. Fox3, D. Ontaneda3
1Cleveland Clinic, Biomedi, Cleveland, United States, 2Cleveland Clinic, Quantitative Health Sciences, Cleveland, United States, 3Cleveland Clinic, Mellen Center for Multiple Sclerosis, Cleveland, United States
Background: Chronic active lesions (CALs) are considered a contributing mechanism of clinical worsening in multiple sclerosis (MS). Slowly-evolving lesions (SELs) have been proposed as an in vivo biomarker for CALs and have been associated with disability worsening. Ibudilast was investigated in progressive MS in a phase II multi-center clinical trial (SPRINT-MS), and ibudilast’s inhibition of phosphodiesterase suggested a potential effect on CALs.
Objective: To evaluate the effect of ibudilast on SELs.
Methods: SPRINT-MS involved brain MRIs every 24 weeks for 96 weeks. Inclusion criteria were either primary or secondary progressive MS according to 2010 criteria and EDSS 3.0-6.5. For this analysis, at least 4 MRIs without scanner change from baseline MRI were required. The analysis involved nonlinear registration of all follow-up MRIs to subject’s baseline MRI to obtain maps of Jacobian determinant. For SEL detection, we performed voxelwise linear regression over time within the baseline T2 lesions. The cutoff between 7.5 and 20%/year was used to determine the SELs. Finally we measured the volumes of voxels meeting these cutoffs. We determined the effect of ibudilast on SEL volume using linear regression with covariate adjustment of baseline T2 lesion volumes (T2LV). We further evaluated the treatment effect in subtypes (PPMS vs SPMS) by interaction term as well as stratified models. Disability progression was evaluated using Cox proportional hazard and log-rank tests with dichotomized and quartiles of SEL volume. R software with survival package was used.
Results: Of 255 randomized patients in the core study, 33 dropped out, 1 had only 3 scans, and 26 had a change in scanner. The remaining 195 patients were analyzed. The mean SEL volumes were 1.08 ml (SD=1.32) in ibudilast and 1.49 (2.00) in placebo. After the baseline T2LV adjustment, ibudilast was associated with a 26% decrease in SEL volume (p=0.004). The interaction between treatment and MS subtype was not significant (p=0.58), and stratified models showed similar treatment effects of in PPMS (30%) and SPMS (21%). There was no significant difference between SEL categories for disability progression in any of the time to event analyses.
Conclusion: We observed a significant treatment effect of ibudilast on SEL. This was consistent with proposed mechanism of action (microglia inflamed in MS) and adds to the efficacy profile of ibudilast in progressive MS