Author Of 3 Presentations
P0187 - A prospective randomized open-label blinded endpoint multicenter non-inferiority study of oral cladribine and rituximab in Multiple Sclerosis (NOR-MS) (ID 1194)
Abstract
Background
Both induction therapy, like oral cladribine, and B-cell depletion therapy, like rituximab, are highly effective disease modulatory treatments (DMTs) in relapsing multiple sclerosis (MS). The high economic costs of the registered DMTs may limit availability of treatment and strain health budgets worldwide.
Oral cladribine is a recently approved DMT in Europe, while rituximab is used off-label, especially in Norway and Sweden. Large observational studies indicate good tolerance and treatment effects in MS and studies from other diseases indicate a good safety profile. However, to our knowledge, no phase three studies have compared rituximab with any established highly effective DMT. Formal safety data is also lacking for rituximab treatment in MS.
Objectives
To perform a prospective randomized open-label blinded endpoint multicenter non-inferiority study. The primary objective is to test whether rituximab is non-inferior to oral cladribine for treatment of relapsing MS.
Methods
In total 264 MS patients with relapsing MS will be recruited from 11 Norwegian centers and followed for 96 weeks. Inclusion criteria are having a relapsing MS diagnosis, age 18-65 years, at least one clinical relapse or one new T2 lesion on MRI within the last year and willingness to use contraception during the study period. Exclusion criteria are contraindications to either treatment, previous use of either or a similar treatment, or treatment with fingolimod or natalizumab (due to risk of rebound activity) within the last six months. The study participants will be treated with either cladribine or rituximab according to current guidelines.
Results
The primary endpoint is difference in number of new or enlarging T2 lesions between the two groups from rebaseline at 12 weeks to the end of the study at 96 weeks. Furthermore, we will study clinical course, blood samples and MRI biomarkers to provide tools for personalized MS treatment. Finally, the health economic consequences of these treatment options will be evaluated. At the time of abstract submission, 55 patients have been included across three study sites. The Covid19 outbreak unfortunately resulted in a temporary halt in inclusion from March to May 2020, but the study has now been reopened. End of study is estimated to fall 2023.
Conclusions
This study will guide clinicians and patients in future treatment choices for MS. The results will provide valuable knowledge concerning treatment strategies and can potentially have a huge impact on the costs of future MS treatments.
P0578 - Five years functional connectivity reorganization without clinical or cognitive decline in MS (ID 755)
Abstract
Background
Multiple sclerosis (MS) is a disease characterized radiologically by the accumulation of lesions in grey and white matter over time throughout the CNS. Accumulating evidence has demonstrated abnormal patterns of brain functional connectivity (FC) in MS patients as compared to healthy controls (HCs). A longitudinal approach that accounts for all alterations in FC following structural damage in MS is warranted to better understand the complex interplay between disease progression and FC reorganization.
Objectives
1) To assess fMRI-based FC anomalies in early MS 2) To determine the relation between FC changes and structural brain damage due to disease progression 3) To study the association between FC changes and cognitive and physical disability.
Methods
Structural MRI and resting-state fMRI were acquired from 76 early relapsing-remitting MS patients at baseline (average disease duration 71.7 months ± 63) and after five years. Ninety-four HCs matched for age and sex were included at baseline. Independent component analysis (ICA) and network modelling were used to measure FC. FC variation was related to expanded disability status scale, timed 25-foot walk test, 9 hole peg test and neuropsychological outcomes. Brain and lesion volumes were quantified using standard methods. We used the 25 independent components obtained from ICA to estimate the longitudinal stability of the brain functional connectome as a proxy for functional reorganization over time. We computed the stability of the brain functional connectome for each MS patient by vectorizing each participant’s whole-brain connectivity matrix. Then, we calculated the within subjects Spearman correlation coefficient between fMRI at baseline and follow-up, obtaining a measure of whole-brain connectome stability that is sensitive to all changes in FC in the follow-up period.
Results
The MS subjects (71% females, mean age 35.3 ± 7.3) were clinically and cognitively stable. Compared to HCs, FC abnormalities were detected within networks and in single connections, mainly in the default mode network and frontoparietal areas, in patients with early MS at baseline. Over time, FC was relatively invariable, but changes in FC were associated with progression of brain atrophy (ρ = 0.39, p = .06). No significant relationship with clinical and cognitive measures or lesion load was detected.
Conclusions
We used the stability of the brain functional connectome as a proxy for FC reorganization. Patients with MS showed altered FC in the early stages of the disease, with FC abnormalities being bidirectional (i.e. increased and decreased FC). Over time, changes in FC, independent of direction, could be related to progression of brain atrophy, which is associated with changes in clinical and cognitive functioning. Connectome stability enables fMRI data to be condensed into a proxy as a cross-sectional and longitudnal individual imaging marker.
P0598 - LesionQuant for assessment of MRI in multiple sclerosis- a promising supplement to the visual scan inspection (ID 670)
Abstract
Background
Quantitative measurements of lesion volume, lesion count, distribution of lesions and brain atrophy have a potentially significant value for evaluating disease progression in multiple sclerosis (MS).
Objectives
We wanted to investigate whether utilizing a software designed for evaluating MRI data in MS would be more sensitive and clinically useful compared to the visual neuro-radiological evaluation.
Methods
A group of 56 MS patients (mean age 35 years, 70 % females and 96 % relapsing-remitting MS) was examined with brain MRI one and five years after being diagosed with MS. The T1 and FLAIR brain MRI sequences for all patients were analyzed using the LesionQuant (LQ) software. The resulting LQ output was compared with data from structured visual evaluations of the MRI scans performed by a neuro-radilogist, includning assessements of atrophy and lesion count. Correlations with clinical tests, like the timed 25- foot walk test (T25-FW), were performed to explore additional value of LQ analyses compared to visual assessments.
Results
Lesion count assessments by LQ and by the neuro-radiologist were significantly correlated one year (cor=0.92, p=2.2x10¯16) and five years (cor=0.84, p=2.7x10¯16) after diagnosis. LQ detected a reduction in whole brain percentile >10 in 10 patients across the time-points, whereas the neuro-radiologist assessment identified six of these. The neuro-radiologist additionally identified five patients with increased atrophy in the follow-up period, all of them displayed decreasing low whole brain percentiles (median 11, range 8-28) in the LQ analysis. A significant positive correlation was identified between lesion volume measured by LQ and test performance of T25-FW both at one year (t=3.08, p=3.2x10¯3) and five years (t=3.72, p=4.8x10¯4) after diagnosis, while we found no association between visual inspection and the clinical tests.
Conclusions
For the number of MS lesions at both time-points, we demonstrated strong correlations between the assessments done by LQ and the neuro-radilogist. Lesion volume evaluated with LQ correlated with T25-FW performance. LQ-analyses were more sensitive in capturing brain atrophy than the visual neuro-radiological evaluation. In conclusion, LQ seems like a promising supplement to the evaluation performed by neuro-radiologists, providing an automated tool for evaluating lesions and brain volume in MS patiens in both a longitudinal and cross-sectional setting.