Faculty Bibliography
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287
Presentation of Neuromyelitis Optica (NMO) in patients from different racial groups: analysis of the global NMOBase Registry [Meeting Abstract]
ISI:000453090805142
ISSN: 0028-3878
CID: 3561712
Anti-Myelin Oligodendrocyte Glycoprotein (MOG) Antibodies in a Patient with Ataxia, Diplopia, and an Enhancing Cerebellar Lesion [Meeting Abstract]
ISI:000453090805156
ISSN: 0028-3878
CID: 3732432
A Case of Progressive Multifocal Leukoencephalopathy in a Patient on Extended Interval Dose Natalizumab [Meeting Abstract]
ISI:000453090804197
ISSN: 0028-3878
CID: 3561752
Effectiveness of alternative dose fingolimod for multiple sclerosis
Background/UNASSIGNED:Fingolimod is a daily oral medication used to treat relapsing multiple sclerosis (MS). Clinicians often adopt less frequent dosing for patients with profound drug-induced lymphopenia or other adverse events. Data on the effectiveness of alternate dose fingolimod are limited. Methods/UNASSIGNED:We conducted a multicenter, retrospective, observational study at 14 sites and identified 170 patients with MS taking alternate doses of fingolimod for ≥1 month. Clinical and radiologic outcomes were collected and compared during daily and alternate fingolimod dosing. Results/UNASSIGNED:< 0.001). Conclusions/UNASSIGNED:These data support the clinical strategy of alternate dosing of fingolimod in patients with good disease control but profound lymphopenia or other adverse events while on daily dose. Classification of Evidence/UNASSIGNED:This study provides Class IV evidence that for patients with MS on daily dose fingolimod with adverse events, alternate dose fingolimod is associated with disease activity similar to daily dose fingolimod.
PMCID:5914753
PMID: 29708225
ISSN: 2163-0402
CID: 3150542
Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
BACKGROUND:modulator, on disability progression in patients with SPMS. METHODS:This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18-60 years) with SPMS and an Expanded Disability Status Scale score of 3·0-6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. FINDINGS:1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65-0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. INTERPRETATION:Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. FUNDING:Novartis Pharma AG.
PMID: 29576505
ISSN: 1474-547x
CID: 5348122
Natalizumab Extended Interval Dosing Is Associated with a Reduction in Progressive Multifocal Leukoencephalopathy (PML) Risk in the Touch (R) Registry [Meeting Abstract]
ISI:000429034600272
ISSN: 1352-4585
CID: 3039222
NATALIZUMAB EXTENDED INTERVAL DOSING (EID) IS ASSOCIATED WITH A SIGNIFICANT REDUCTION IN PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) RISK COMPARED WITH STANDARD INTERVAL DOSING (SID) IN THE TOUCH (R) PRESCRIBING PROGRAM [Meeting Abstract]
ISI:000438056200071
ISSN: 0022-3050
CID: 5191992
Longitudinal study of multiple sclerosis lesions using ultra-high field (7T) multiparametric MR imaging
Pathophysiology of multiple sclerosis (MS) lesions is dynamic and changes over time. The purpose of this exploratory study was to determine the longitudinal changes in MS lesions over time on ultra-high field MR imaging. Nine patients with MS underwent high-resolution 3D-susceptibility weighted imaging (SWI) and 2D-gradient-echo-T2*-weighted imaging on 7T MRI at baseline and after ~2.4 years of follow-up. Morphologic imaging characteristics, signal intensity patterns and quantitative susceptibility mapping (QSM) values of lesions were recorded at both time points. Lesions were classified as "iron-laden" if they demonstrated hypointense signal on T2*-weighted images and/or SWI as well as hyperintense signal on QSM. Lesions were considered "non-iron-laden" if they were hyperintense on T2*/SWI and isointense or hyperintense on QSM. Total of 162 non-iron-laden and 29 iron-laden lesions were observed at baseline. No change in baseline lesion size during follow up was recorded in 92.7%; no change in lesion-vessel relationship in 86.5%; and no change in signal intensity pattern in 96.9% of lesions. Three lesions which were non-iron-laden at baseline, exhibited iron at follow-up. In two iron-laden lesions, redistribution of iron content was observed at follow-up. Two-thirds of these iron-laden lesions showed an increase in QSM at follow-up relative to baseline, and the remaining one-third exhibited decrease in QSM. Most of the newly formed lesions (11/13, 84.6%) at follow-up were iron-laden. 7T multiparametric MRI is a useful tool for tracking the evolution of MS lesions, especially with regard to changes in iron content.
PMID: 30212476
ISSN: 1932-6203
CID: 3277882
Short-term disability progression in two multiethnic multiple sclerosis centers in the treatment era
Background/UNASSIGNED:Short-term disease progression is well documented in clinical trials, but there are limited published data on disease course in real-life practice. Methods/UNASSIGNED:Patient-Determined Disease Steps (PDDS). Clinicians recorded disease subtype and relapse status at each visit, but did not rate disability. PMSSS change from the first to the last visit was calculated for the cohort as a whole and for subgroups of interest. Multivariable regression models were constructed for predicting final PMSSS based on readily available predictor variables collected at the initial visit and relapse history during follow up. Results/UNASSIGNED:0.28). The only major predictor of final PMSSS was the initial PMSSS. Demographic variables (age, sex, race) or relapse status did not predict final severity score. Conclusions/UNASSIGNED:Baseline disability in two MS clinics was much lower than in the reference population from which PMSSS was derived. We observed no discernable slowing of disability accumulation during the short-term follow up in our cohort compared with the reference cohort. Overwhelmingly the most important predictor of final disease severity rank score was the initial disease severity rank score.
PMCID:6134488
PMID: 30214486
ISSN: 1756-2856
CID: 3277922
Clinical Reasoning: A patient with a history of encephalomyelitis and recurrent optic neuritis
PMCID:5679419
PMID: 29109139
ISSN: 1526-632x
CID: 2772062
