Faculty Bibliography
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280
Mortality in neuromyelitis optica is strongly associated with African ancestry
PMCID:5994702
PMID: 29892608
ISSN: 2332-7812
CID: 3167112
Extended interval dosing (EID) of natalizumab is associated with significantly lower progressive multifocal leukoencephalopathy (PML) risk: Sensitivity and post hoc analyses from the TOUCH registry [Meeting Abstract]
Background and aims: Natalizumab, approved for intravenous 300mg every 4 weeks dosing, is associated with a risk of PML. Previous analyses of US TOUCH registry data found that, in anti-JC virus antibody positive (JCV Ab+) patients, natalizumab EID was associated with significantly lower PML risk compared with standard interval dosing (SID; Table). Those analyses were limited to patients with known JCV Ab seropositive status and excluded patients with infusions at >12-week intervals (ie, dosing gaps). Sensitivity and post-hoc analyses were conducted to explore the robustness of these results. Methods: In the previous primary analysis, SID was based on average dosing intervals (ADIs) of >=3 to <5 weeks; EID was based on ADIs of >5 to <=12 weeks. In prespecified sensitivity analyses, alternative EID definitions and inclusion of PML cases occurring pre-2012, prior to JCV Ab testing, was evaluated. A post hoc analysis included patients with dosing gaps. EID and SID PML hazard ratios (HRs) were compared with covariate (age, sex, prior immunosuppressant use, initiation calendar year, and infusion number)-adjusted Cox regression models and Kaplan-Meier estimates. Results: Across all sensitivity and post-hoc analyses, HRs and 95% CIs were similar to those in the primary analysis. Conclusion: In the US, natalizumab EID is associated with a statistically significant, clinically meaningful lower PML risk in JCV Ab+ patients compared with SID; changes in EID definition and inclusion/exclusion criteria did not reveal differences from the primary analysis. As TOUCH does not collect effectiveness data, EID's benefit-risk could not be evaluated
EMBASE:623298529
ISSN: 1468-1331
CID: 3238952
Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with optic neuritis and seizures
We describe four patients who experienced optic neuritis (ON) and seizures and were found to have antibodies to myelin oligodendrocyte glycoprotein (MOG) in serum. The index case was a previously healthy 39-year-old man who developed steroid dependent ON and had a generalized seizure when steroids were tapered. He tested positive for antibodies to MOG. We have reviewed the charts of all 11 anti-MOG antibody positive patients in our practice and found that 4 patients, all of whom had experienced one or more episodes of ON, also had a generalized seizure during the course of their illness. In 2 patients - including the index case - seizure occurred during steroid taper and in 2 others at the time of an episode of acute disseminated encephalomyelitis (ADEM). Association of anti-MOG antibodies and relapsing demyelinating disorders of the central nervous system is increasingly recognized. Testing for anti-MOG antibodies should be considered in patients with optic neuritis and seizures, especially in those with who also have a history of ADEM.
PMID: 29571858
ISSN: 1878-5883
CID: 3010732
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
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
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
