Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis

To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort

Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis

Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear. Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms. Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score > 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores. Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37,p < 0.001) and EDSS (beta = 0.16,p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89,p = 0.01) and EDSS (beta = -0.06,p < 0.001). Neither presentation was associated with changes in relapse risk. Conclusion: Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach

Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis

Background Age at onset (AAO) in multiple sclerosis (MS) is an important marker of disease severity and may have prognostic significance. Understanding what factors can influence AAO may shed light on the aetiology of this complex disease, and have applications in the diagnostic process

Comparative efficacy of first-line natalizumab vs IFN-β or glatiramer acetate in relapsing MS

Background: We compared efficacy and treatment persistence in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS) initiating natalizumab compared with interferon-β (IFN-β)/glatiramer acetate (GA) therapies, using propensity score-matched cohorts from observational multiple sclerosis registries. Methods: The study population initiated IFN-β/GA in the MSBase Registry or natalizumab in the Tysabri Observational Program, had ≥3 months of on-treatment follow-up, and had active RRMS, defined as ≥1 gadolinium-enhancing lesion on cerebral MRI at baseline or ≥1 relapse within the 12 months prior to baseline. Baseline demographics and disease characteristics were balanced between propensity-matched groups. Annualized relapse rate (ARR), time to first relapse, treatment persistence, and disability outcomes were compared between matched treatment arms in the total population (n 366/group) and subgroups with higher baseline disease activity. Results: First-line natalizumab was associated with a 68% relative reduction in ARR from a mean (SD) of 0.63 (0.92) on IFN-β/GA to 0.20 (0.63) (p [signed-rank] &lt; 0.0001), a 64% reduction in the rate of first relapse (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.28-0.47; p &lt; 0.001), and a 27% reduction in the rate of discontinuation (HR 0.73, 95% CI 0.58-0.93; p 0.01), compared with first-line IFN-β/GA therapy. Confirmed disability progression and area under the Expanded Disability Status Scale-time curve analyses were not significant. Similar relapse and treatment persistence results were observed in each of the higher disease activity subgroups. Conclusions: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse and treatment persistence outcomes compared to first-line IFN-β/GA. This needs to be balanced against the risk of progressive multifocal leukoencephalopathy in natalizumab-treated patients. Classification of evidence: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse rates and treatment persistence outcomes compared to first-line IFN-β/GA

Comparative efficacy of first-line natalizumab vs IFN-β or glatiramer acetate in relapsing MS

Background: We compared efficacy and treatment persistence in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS) initiating natalizumab compared with interferon-β (IFN-β)/glatiramer acetate (GA) therapies, using propensity score-matched cohorts from observational multiple sclerosis registries. Methods: The study population initiated IFN-β/GA in the MSBase Registry or natalizumab in the Tysabri Observational Program, had ≥3 months of on-treatment follow-up, and had active RRMS, defined as ≥1 gadolinium-enhancing lesion on cerebral MRI at baseline or ≥1 relapse within the 12 months prior to baseline. Baseline demographics and disease characteristics were balanced between propensity-matched groups. Annualized relapse rate (ARR), time to first relapse, treatment persistence, and disability outcomes were compared between matched treatment arms in the total population (n 366/group) and subgroups with higher baseline disease activity. Results: First-line natalizumab was associated with a 68% relative reduction in ARR from a mean (SD) of 0.63 (0.92) on IFN-β/GA to 0.20 (0.63) (p [signed-rank] < 0.0001), a 64% reduction in the rate of first relapse (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.28-0.47; p < 0.001), and a 27% reduction in the rate of discontinuation (HR 0.73, 95% CI 0.58-0.93; p 0.01), compared with first-line IFN-β/GA therapy. Confirmed disability progression and area under the Expanded Disability Status Scale-time curve analyses were not significant. Similar relapse and treatment persistence results were observed in each of the higher disease activity subgroups. Conclusions: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse and treatment persistence outcomes compared to first-line IFN-β/GA. This needs to be balanced against the risk of progressive multifocal leukoencephalopathy in natalizumab-treated patients. Classification of evidence: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse rates and treatment persistence outcomes compared to first-line IFN-β/GA

Long-term outcomes in patients presenting with optic neuritis: Analyses of the MSBase registry

Background: Short-term outcomes of optic neuritis (ON) have been well characterized. Limited data exists on longer-term visual outcomes in patients who present with ON. The large MSBase registry allows for characterization of long-term visual outcomes after ON

The trigger and data acquisition for the NEMO-Phase 2 tower

In the framework of the Phase 2 of the NEMO neutrino telescope project, a tower with 32 optical modules is being operated since march 2013. A new scalable Trigger and Data Acquisition System (TriDAS) has been developed and extensively tested with the data from this tower. Adopting the all-data-to-shore concept, the NEMO TriDAS is optimized to deal with a continuous data-stream from off-shore to on-shore with a large bandwidth. The TriDAS consists of four computing layers: (i) data aggregation of isochronal hits from all optical modules; (ii) data filtering by means of concurrent trigger algorithms; (iii) composition of the filtered events into post-trigger files; (iv) persistent data storage. The TriDAS implementation is reported together with a review of dedicated on-line monitoring tools

Natalizumab, Fingolimod, and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis

OBJECTIVE: To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort. METHODS: Using data from the MSBase Registry, we included pregnancies conceived after December 31, 2010, in women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses. RESULTS: We included 1,998 pregnancies from 1,619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% confidence interval 0.27–0.32), fell to 0.19 (0.14–0.24) in the third trimester, and increased to 0.59 (0.51–0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28–0.49) and 0.29 (0.22–0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (odds ratio 0.76 per month [0.60–0.95], p = 0.017). DMT reinitiation with natalizumab protected against postpartum relapse (hazard ratio [HR] 0.11 [0.04–0.32], p < 0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41–0.91], p = 0.016). We found that 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum. CONCLUSION: Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation with early reinitiation after delivery is an effective option to minimize relapse risks. Strategies of disease-modifying therapy use have to be balanced against potential fetal/neonatal complications