Faculty Bibliography
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257
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
PML in immunocompromised patient populations : historical context
ORIGINAL:0016173
ISSN: 1075-4598
CID: 5347912
Multiple Sclerosis and Cognition: The Impact of Psychotropic Medications [Meeting Abstract]
ISI:000429034600315
ISSN: 1352-4585
CID: 5343752
Among real-world multiple sclerosis patients that experience delayed-release dimethyl fumarate-associated lymphopenia, meaningful lymphocyte reconstitution occurs within 3 months after discontinuation of delayed-release dimethyl fumarate [Meeting Abstract]
ISI:000446861401547
ISSN: 1352-4585
CID: 5343852
Periodic limb movements in people with multiple sclerosis who report fatigue: polysomnography study in a large cohort [Meeting Abstract]
ISI:000446861400236
ISSN: 1352-4585
CID: 5343762
Multiple sclerosis: brain atrophy and multi-domain computerized cognitive testing - a longitudinal investigation of changes in disease impact relating structure to function [Meeting Abstract]
ISI:000446861400249
ISSN: 1352-4585
CID: 5343772
Manual dexterity and computerized cognitive testing in people with multiple sclerosis: motor domain reflects more than just what is in the hand [Meeting Abstract]
ISI:000446861400251
ISSN: 1352-4585
CID: 5343782
Multiple sclerosis, fatigue and disease modifying therapy impact: differences in sleep architecture in patients with multiple sclerosis - Copaxone versus interferons [Meeting Abstract]
ISI:000446861400498
ISSN: 1352-4585
CID: 5343792
The relationship between obstructive sleep apnea and age, gender, EDSS, disease duration, and BMI in people with multiple sclerosis who report fatigue: more than size matters [Meeting Abstract]
ISI:000446861401374
ISSN: 1352-4585
CID: 5343832
Investigation into the relationship between digital brain volume and computerized screening assessment of cognitive function in people with multiple sclerosis: objective analytics to quantify disease impact [Meeting Abstract]
ISI:000446861402127
ISSN: 1352-4585
CID: 5343922
