To determine whether ibudilast has an effect on brain volume and new lesions in progressive forms of multiple sclerosis (MS).
A randomized, placebo-controlled, blinded study evaluated ibudilast at a ...dose of up to 100 mg over 96 weeks in primary and secondary progressive MS. In this secondary analysis of a previously reported trial, secondary and tertiary endpoints included gray matter atrophy, new or enlarging T2 lesions as measured every 24 weeks, and new T1 hypointensities at 96 weeks. Whole brain atrophy measured by structural image evaluation, using normalization, of atrophy (SIENA) was a sensitivity analysis.
A total of 129 participants were assigned to ibudilast and 126 to placebo. New or enlarging T2 lesions were observed in 37.2% on ibudilast and 29.0% on placebo (
= 0.82). New T1 hypointense lesions at 96 weeks were observed in 33.3% on ibudilast and 23.5% on placebo (
= 0.11). Gray matter atrophy was reduced by 35% for those on ibudilast vs placebo (
= 0.038). Progression of whole brain atrophy by SIENA was slowed by 20% in the ibudilast group compared with placebo (
= 0.08).
Ibudilast treatment was associated with a reduction in gray matter atrophy. Ibudilast treatment was not associated with a reduction in new or enlarging T2 lesions or new T1 lesions. An effect on brain volume contributes to prior data that ibudilast appears to affect markers associated with neurodegenerative processes, but not inflammatory processes.
This study provides Class II evidence that for people with MS, ibudilast does not significantly reduce new or enlarging T2 lesions or new T1 lesions.
Summary Background Most patients with multiple sclerosis without previous optic neuritis have thinner retinal layers than healthy controls. We assessed the role of peripapillary retinal nerve fibre ...layer (pRNFL) thickness and macular volume in eyes with no history of optic neuritis as a biomarker of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available. Methods In this multicentre, cohort study, we collected data about patients (age ≥16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis, and progressive multiple sclerosis. Patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Netherlands, Canada, and the USA, with the first cohort starting in 2008 and the latest cohort starting in 2013. We assessed disability worsening using the Expanded Disability Status Scale (EDSS). The pRNFL thickness and macular volume were assessed once at study entry (baseline) by optical coherence tomography (OCT) and was calculated as the mean value of both eyes without optic neuritis for patients without a history of optic neuritis or the value of the non-optic neuritis eye for patients with previous unilateral optic neuritis. Researchers who did the OCT at baseline were masked to EDSS results and the researchers assessing disability with EDSS were masked to OCT results. We estimated the association of pRNFL thickness or macular volume at baseline in eyes without optic neuritis with the risk of subsequent disability worsening by use of proportional hazards models that included OCT metrics and age, disease duration, disability, presence of previous unilateral optic neuritis, and use of disease-modifying therapies as covariates. Findings 879 patients with clinically isolated syndrome (n=74), relapsing-remitting multiple sclerosis (n=664), or progressive multiple sclerosis (n=141) were included in the primary analyses. Disability worsening occurred in 252 (29%) of 879 patients with multiple sclerosis after a median follow-up of 2·0 years (range 0·5–5 years). Patients with a pRNFL of less than or equal to 87 μm or less than or equal to 88 μm (measured with Spectralis or Cirrus OCT devices) had double the risk of disability worsening at any time after the first and up to the third years of follow-up (hazard ratio 2·06, 95% CI 1·36–3·11; p=0·001), and the risk was increased by nearly four times after the third and up to the fifth years of follow-up (3·81, 1·63–8·91; p=0·002). We did not identify meaningful associations for macular volume. Interpretation Our results provide evidence of the usefulness of monitoring pRNFL thickness by OCT for prediction of the risk of disability worsening with time in patients with multiple sclerosis. Funding Instituto de Salud Carlos III.
The coronavirus disease 2019 (COVID-19) pandemic has catalyzed the rapid adoption of telemedicine which encompasses synchronous and asynchronous interactions between patients and providers. In order ...to facilitate this rapid deployment, there has been numerous regulatory changes to ensure caregivers can effectively communicate with patients during this time. We illustrate a model where people, processes, and technology work together to address the comprehensive needs of multiple sclerosis (MS) patients. We provide a template for how multidisciplinary, academic practices can implement a rapid shift to virtual management during the pandemic using existing infrastructure that can be widely adopted to care for patients with chronic diseases. Telemedicine was incorporated into our entire practice, which encompasses neurology, rehabilitation, advanced practice providers, fellows, social work, and behavioral medicine. Our patient satisfaction results remained stable across almost all domains when compared to survey results from our typical, in-office visits. Our experience demonstrates telemedicine’s transformative potential in successfully managing a multidisciplinary MS clinic during the time of a pandemic and outlines a potential path for other practices to follow.
Background:
In order to provide patient center care, our multiple sclerosis (MS) clinic assesses patient concerns before clinical encounters, first by asking the optional qualitative question “What ...is the most important thing you what your health-care provider to know today” (most important concern of the patient MIPC) and then completing quantitative patient-reported outcome measures (PROMs) including Quality of Life in Neurological Disorders (Neuro-QoL). Both sets of questions are designed to facilitate encounters that address patients’ values and preferences.
Objective:
Determine whether the qualitative MIPC responses provided unique information not included in PROMs or clinical assessments.
Methods:
We randomly selected 400 first-time MIPC responders and 400 first-time MIPC nonresponders from 2788 participants in our database. We categorized MIPC responses by content and number of unique concerns and appended them to the Neuro-QoL framework. Nonresponders were compared to those who provided 1 and 2 or more responses.
Results:
Several MIPCs MS symptoms categories were added to the Neuro-QoL Physical domain. Most important concern of the patients work and cost-of-care categories were added to the Social Domain. Domains regarding treatment satisfaction and disease management were added. Two hundred thirty (58%) MIPC respondents reported 1 concern, 140 (35%) expressed 2 to 6 concerns, and 30 (7%) reported MS-unrelated concerns and not analyzed. Physical symptoms were the most common MIPC (69.9%). Respondents with more concerns were more likely African American, lacked private insurance, and worse disability.
Conclusions:
Importantly, MIPC responders described idiosyncratic symptoms, disease management, and social concerns not included in the PROMS, suggesting the MIPC question offered patients a unique opportunity to share specific concerns with their providers.
MR imaging is an integral part of multiple sclerosis (MS) clinical trials. It provides the primary efficacy outcome of preliminary proof-of-concept studies and important corroborating data as ...secondary and exploratory outcomes in pivotal trials. At all stages of drug development, MR imaging provides important information on the kinetics and magnitude of treatment effect and insight into potential mechanisms of action. Attention to issues in scan acquisition, quantitative image processing, and statistical analysis is critical to generate high-quality data. Although it is unlikely that one single outcome measure can capture all aspects of the MS disease process, there is potential for MR imaging outcomes to evaluate inflammatory and degenerative components within clinical trials.
Deep gray matter damage may be an important component of the multiple sclerosis (MS) disease process. We tested whether caudate atrophy occurs in MS, and whether it correlates with conventional MRI ...or clinical markers of disease progression. Caudate nuclei of 24 MS patients and 10 age-matched healthy controls were traced, normalized, reconstructed and visualized from MRI scans. Normalized bicaudate volume was 19% lower in MS controls ( p< 0.001), an effect that persisted after adjusting for whole-brain atrophy ( p< 0.008). Caudate volume did not correlate with disease duration, physical disability score, whole-brain atrophy, or total T2 hyperintense or T1 hypointense lesion load (all p > 0.05). We conclude that selective caudate atrophy is associated with MS and may occur through direct mechanisms.
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