Effect of peginterferon beta-1a on MRI measures and achieving no evidence of disease activity: results from a randomized controlled trial in relapsing-remitting multiple sclerosisReport as inadecuate




Effect of peginterferon beta-1a on MRI measures and achieving no evidence of disease activity: results from a randomized controlled trial in relapsing-remitting multiple sclerosis - Download this document for free, or read online. Document in PDF available to download.

BMC Neurology

, 14:240

Demyelinating diseases

Abstract

BackgroundSubcutaneous peginterferon beta-1a provided clinical benefits at Year 1 placebo-controlled period of the 2-Year Phase 3 ADVANCE study in relapsing-remitting multiple sclerosis RRMS. Here we report the effect of peginterferon beta-1a on brain magnetic resonance imaging MRI lesions, and no evidence of disease activity NEDA; absence of clinical relapses and 12-week confirmed disability progression and MRI gadolinium-enhancing, and new or newly-enlarging T2 hyperintense lesions disease activity during Year 1.

MethodsRRMS patients 18–65 years; Expanded Disability Status Scale score ≤5 were randomized to double-blind placebo or peginterferon beta-1a 125 μg every 2 or 4 weeks. Sensitivity analyses of last observation carried forward and composite disease activity using minimal MRI allowance definitions were conducted.

Results1512 patients were randomized and dosed placebo n = 500; peginterferon beta-1a every 2 n = 512 or 4 n = 500 weeks. Every 2 week dosing significantly reduced, versus placebo and every 4 week dosing, the number of new or newly-enlarging T2 hyperintense lesions at Weeks 24 by 61% and 51%, respectively and 48 secondary endpoint; by 67% and 54%, respectively; all p < 0.0001. Every 2 week dosing also provided significant reductions versus placebo and every 4 week dosing in the number of new T1 hypointense, gadolinium-enhancing, and new active gadolinium-enhancing plus non-enhancing new T2 lesions all p < 0.0001, as well as the volume of T2 and T1 lesions p < 0.05 at Weeks 24 and 48. Significantly more patients dosed every 2 weeks had NEDA versus placebo and every 4 weeks all p < 0.01 from baseline to Week 48 33.9% versus 15.1% and 21.5%, respectively odds ratios, ORs: 2.89 and 1.87, from baseline to Week 24 41.0% versus 21.9% and 30.7%, ORs: 2.47 and 1.57 and from Week 24 to Week 48 60.2% versus 28.9% and 36.6%, ORs: 3.71 and 2.62. Consistent results were seen when allowing for minimal MRI activity.

ConclusionDuring Year 1 of ADVANCE, significantly more RRMS patients receiving peginterferon beta-1a every 2 weeks had NEDA, and early and sustained improvements in all MRI endpoints, versus placebo and every 4 week dosing. NEDA sensitivity analyses align with switch strategies in clinical practice settings and provide insight into future responders-non-responders.

Trial registrationClinicalTrials.gov: https:-clinicaltrials.gov-ct2-show-NCT00906399

KeywordsClinical trial Multiple sclerosis Pegylation Interferon AbbreviationsANCOVAAnalysis of covariance

EDSSExpanded Disability Status Scale

FMDAFreedom from measured disease activity

Gd+Gadolinium-enhancing

IFNInterferon

ITTIntention-to-treat

LOCFLast observation carried forward

MRIMagnetic resonance imaging

MSMultiple sclerosis

NEDANo evidence of disease activity

OROdds ratio

PEGPolyethyleneglycol

RRMSRelapsing-remitting MS

SCSubcutaneous

Electronic supplementary materialThe online version of this article doi:10.1186-s12883-014-0240-x contains supplementary material, which is available to authorized users.

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Author: Douglas L Arnold - Peter A Calabresi - Bernd C Kieseier - Sarah I Sheikh - Aaron Deykin - Ying Zhu - Shifang Liu - Xiao

Source: https://link.springer.com/







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