Background

Background: An improved understanding of the impact of demyelination on multiple sclerosis (MS) related cognitive impairment is crucial for targeting and testing therapies with the potential to slow cognitive decline. Demyelination can be assessed using myelin water imaging, a quantitative magnetic resonance imaging (MRI) technique that measures signal from water in the myelin bilayers, providing a specific measure of myelin (myelin water fraction, MWF).

Objectives

Objective: To determine if there is an anatomical-functional relationship between myelin content and location with cognitive performance.

Methods

Methods: 76 MS participants (mean (SD) age:50.4y(10.6y), 51F) underwent T2 relaxation imaging to calculate MWF maps and cognitive testing (Symbol Digit Modalities Test (SDMT); Selective Reminding Test (SRT); Controlled Oral Word Association Test (COWAT); Brief Visuospatial Memory Test-Revised (BVMT-R)). Nonparametric permutation testing with FSL Randomise was used to determine which white matter (WM) MWF voxels were associated with cognitive test performance for each test (p<0.01, after multiple comparisons correction), creating test-specific maps of associated WM areas. Pearson ́s correlations assessed relationships between mean MWF in the cognitive test-specific WM areas and respective test scores. MS patients were categorized into cognitively impaired, mildly impaired and cognitively preserved groups based on published norms. Kruskal Wallis ANOVA with post hoc pairwise comparisons investigated mean MWF differences between cognitive groups.

Results

Results: MWF in several WM areas was significantly associated with SDMT, SRT and BVMT-R scores but not the COWAT. All tests found voxels within the corona radiata, posterior thalamic radiation and parts of the corpus callosum significant. Unique WM areas were the inferior longitudinal fasciculus and anterior cingulum for SDMT and the retrolenticular part of the internal capsule for the BVMT-R. Mean MWF in the test-specific WM areas correlated significantly with performance on the SDMT (r=0.58, p= 4.11 x 10^-8), SRT (r=0.56, p= 4.14 x 10^-7) and BVMT-R (r=0.56, p= 1.0 x 10^-6). Mean MWF in the test-specific WM areas was significantly lower in the cognitively impaired group relative to the cognitively preserved group (p<0.01).

Conclusions

Conclusions: There is an anatomical-functional relationship between myelin damage and cognitive performance in MS with unique WM patterns for different cognitive domains.

Background

People with antibodies to myelin oligodendrocyte glycoprotein (MOG) using reliable cell-based assays have heterogeneous course. Best management practices and outcome predictors are still uncertain.

Objectives

This study aimed to assess the treatment experience in a relapsing MOG positive cohort and the impact on disability accrual.

Methods

Retrospective chart review of (aquaporin4 negative) MOG antibody positive patients at University of British Columbia Multiple Sclerosis Clinic with relapsing disease, and minimum 1year follow-up.

Results

Of 49 MOG positive patients, 37(64.8% female) met inclusion criteria. Median age was 26 years (range 3-62; 10 pediatric cases) with median follow-up of 6years(range 1-36). Median time to second disease episode from first was 12 months (range 1-228); and to third (n=27) was 25 months (range 3-312). Median number total disease episodes was 3 (range 2-10).

For some, management decisions were initiated prior to MOG diagnosis. At first disease presentation 35/37 patients received acute therapy but only 1 started chronic therapy. First-line chronic therapies were later started in another 30 patients; in 35%(13/37) after second disease episode, and at the third in 27%(10/37). Most common were azathioprine(61%) and rituximab(19%). Sixteen patients(52%) required second line therapy, mostly due to adverse effects(62.5%) or disease activity(31%). Most common second line therapies were mycophenolate mofetil (MMF) or rituximab. Three patients required third line therapy.

17/37 patients had good outcome (EDSS<2) at last follow-up despite relapsing course, whilst 20(54%) had residual disability. Onset clinical phenotype distribution was similar between these two outcomes. 5% had persistent disability from disease onset, but mostly this developed from the second(19%) or third(16%) episode. 4/6 untreated patients had good outcome. Only 30% of the pediatric cohort vs 63% of the adult cohort had EDSS ≥2.0.

Conclusions

Chronic therapy was not typically started at disease onset, mostly due to initial absence of diagnosis. Azathioprine, MMF and rituximab were all effective therapies. Azathioprine was associated with high proportion of intolerance. Approximately half of patients recovered well from the initial episode; the rest accrued disability, typically from second or third disease episode, independent of clinical phenotype at onset. Further studies are required to identify factors influencing disability accrual, to enable earlier effective treatment in those at highest risk.

Background

Cladribine tablets were approved in Canada in November 2017. All patients prescribed cladribine tablets in Canada are enrolled upon their consent in the adveva patient support program (PSP), which provides drug education, assistance with reimbursement and patient support services.

Objectives

To examine the demographics and treatment history of patients initiating cladribine tablets in Canada, assess the discontinuation rate over the two-year treatment and describe reported adverse events (AEs).

Methods

Analysis of data routinely collected by adveva nurses and all reported AEs from Dec2017 to Jan2020. Patients were included if they consented to enroll in the adveva PSP. They were contacted at enrollment and periodically therafter. Follow-up stopped when treatment was completed/discontinued.

Results

Overall, 1864 patients enrolled in the program; 1373 were female (74.4%) and mean age was 41.54 years (standard deviation [SD]: 10.34). None of the patients were treatment naïve; most (n=1191; 63.9%) had received only one prior disease modifying drug (DMD). The most recent prior DMDs were glatiramer acetate (23.1%), dimethyl fumarate (20.4%), teriflunomide (16.5%), fingolimod (10.9%), and subcutaneous interferon beta-1a (10.4%). Of 1864 enrolled, 1679 (90.1%) had completed pre-treatment evaluation. Of those, 1415 (84.3%) started year-1. Among those, 483 (34.1%) started year-2 and 394 (27.8%) completed it. Mean time to year-2 initiation was 12.75 (SD: 1.27) months. Among all patients who had started year-1 treatment, 38 (2.69%) reported discontinuation. Among those, 26.3% discontinued within <6 months, 52.6% between 6-12 months and 21.1% at ≥12 months. Main reported reasons were: 28.9% unknown, 21.1% AE other than flu-like syndrome and lymphopenia, 18.4% worsening disease, 10.5% patients decision, and 10.5% family planning/pregnant. A total of 843 patients (59.6%) reported at least one AE. Among the total AEs report (n= 3525)the most frequent were fatigue (8.0%), headache (5.4%), nausea (4.7%), and lymphocytopenia (2.5%).

Conclusions

The Canadian adveva program presented a high enrolment rate. Cladribine tablets were associated with a high continuation rate and most patients successfully self-adminstered the drug. Reported adverse events were not severe.