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 sclerosisReportar como inadecuado

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BMC Neurology

, 14:240

Demyelinating diseases


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




LOCFLast observation carried forward

MRIMagnetic resonance imaging

MSMultiple sclerosis

NEDANo evidence of disease activity

OROdds ratio


RRMSRelapsing-remitting MS


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

Fuente: https://link.springer.com/

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