PEGylated Interferon Beta-1a Pharmacokinetics, Pharmacodynamics, and Safety in Subjects with Normal or Impaired Renal Function (P06.165)

Hu, Xiheng; Seddighzadeh, Ali; Stecher, Scott; Miller, Larisa; Zhu, Ying; Hung, Serena

doi:10.1212/wnl.78.1_meetingabstracts.p06.165

Cited by 2 publications

(3 citation statements)

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“…BSA, BMI and weight showed weak correlation ( r 2 ≈ 0.3), indicating an inverse correlation between body size and peginterferon beta-1a exposure. CL cr also correlated inversely with AUC(0,τ) ( r 2 = 0.24), consistent with our previous report 6 . There was almost no correlation between peginterferon beta-1a exposure and age or gender.…”

Section: Resultssupporting

confidence: 92%

“…Correlations between AUC(0,τ) (mean of week 4 and 24) and selected baseline demographic characteristics (age, gender, weight, body mass index [BMI] and body surface area [BSA]) were examined, using a linear regression analysis. As renal function has been shown to affect clearance of peginterferon beta-1a 6 , correlation between AUC over the dosing period (AUC(0,τ)) and creatinine clearance (CL cr ) rates, estimated by the Cockcroft−Gault equation 7 , was also examined. The impact of treatment-emergent antibodies on peginterferon beta-1a exposure was assessed by comparing the individual parameters in antibody positive (up to week 24) subjects with the respective group median values, as well as via visual inspection of sparse PK concentration–time plot stratified by antibody status.…”

Section: Methodsmentioning

confidence: 99%

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Pharmacokinetics and pharmacodynamics of peginterferon beta‐1a in patients with relapsing‐remitting multiple sclerosis in the randomized ADVANCE study

Cui

White

et al. 2015

Brit J Clinical Pharma

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AimsTo evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of subcutaneous peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis (RRMS) in the phase 3 ADVANCE study (n = 1512).MethodsDuring year 1, patients were randomized (1:1:1) to placebo or peginterferon beta-1a 125 μg every 2 or 4 weeks. After year 1, patients randomized to placebo were re-randomized to 125 μg peginterferon beta-1a administered every 2 weeks or every 4 weeks for year 2. Patients randomized to peginterferon beta-1a in year 1 remained on the same dosing regimen in year 2. Intensive blood samples for PK and PD (neopterin elevation; a biomarker of pharmacological activity induced by interferon beta-1a) measurements were collected from 44 patients pre-dosing and at intervals over 240 h post-dosing at weeks 4 and 24. Sparse samples were collected from all patients after each dosing at weeks 4, 12, 24, 56 and 84.ResultsThe PK profile of peginterferon beta-1a did not change over time or between dosing regimens. No accumulation was observed. Peak serum concentrations were reached 1–1.5 days post-dosing, with a mono-phasic decline and a median half-life of approximately 2–3 days. Dosing every 2 weeks provided approximately two-fold greater monthly cumulative area under the curve than every 4 weeks. Neopterin elevation was sustained for 10−14 days following each dose, indicating doubled cumulative duration of pharmacological activity for dosing every 2 weeks vs. every 4 weeks.ConclusionsThese PK/PD profiles potentially explain the enhanced efficacy of dosing every 2 weeks in patients with RRMS.

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Section: Resultssupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of peginterferon beta‐1a in patients with relapsing‐remitting multiple sclerosis in the randomized ADVANCE study

Cui

White

et al. 2015

Brit J Clinical Pharma

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“…By altering its pharmacokinetics and pharmacodynamics this approach allows for a reduced dosing frequency of interferon β1a [Kieseier and Calabresi, 2012]. Two phase I studies showed an improved pharmacokinetic and pharmacodynamic profile of peginterferon β1a compared with intramuscular interferon β1a [Hu et al 2011, 2012].…”

Section: Introductionmentioning

confidence: 99%

An update on the evidence base for peginterferon β1a in the treatment of relapsing–remitting multiple sclerosis

Bhargava

Newsome

2016

Ther Adv Neurol Disord

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Peginterferon β1a is a modified form of interferon β1a with a polyethylene glycol (PEG) group attached to the α-amino group of the N terminus of the interferon molecule. This modification alters the pharmacokinetic and pharmacodynamic properties of interferon β1a, enabling reduced frequency of dosing and may also result in reduced immunogenicity of the interferon β1a molecule. The efficacy of peginterferon β1a 125 µg administered subcutaneously every 2 or 4 weeks was demonstrated at the end of the placebo-controlled period in the phase III ADVANCE study; both dosing regimens met their primary endpoint of reducing annualized relapse rate (ARR) compared with placebo. Peginterferon β1a administered every 2 weeks resulted in a more robust treatment effect on ARR, sustained disability progression and magnetic resonance imaging endpoints (new or enlarging T2 lesions and gadolinium-enhanced lesions) than peginterferon β1a every 4 weeks. Further reductions in the ARR with additional positive impact on magnetic resonance imaging outcomes were noted in year 2 of the ADVANCE study with the every 2-week dosing regimen. An adverse-effect profile similar to other interferon β formulations coupled with the advantage of a significant reduction in the number of injections, could lead to improved long-term adherence to peginterferon β1a. We review the evidence base for the role of peginterferon β1a in the treatment of relapsing-remitting multiple sclerosis.

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PEGylated Interferon Beta-1a Pharmacokinetics, Pharmacodynamics, and Safety in Subjects with Normal or Impaired Renal Function (P06.165)

Cited by 2 publications

References 0 publications

Pharmacokinetics and pharmacodynamics of peginterferon beta‐1a in patients with relapsing‐remitting multiple sclerosis in the randomized ADVANCE study

Pharmacokinetics and pharmacodynamics of peginterferon beta‐1a in patients with relapsing‐remitting multiple sclerosis in the randomized ADVANCE study

An update on the evidence base for peginterferon β1a in the treatment of relapsing–remitting multiple sclerosis

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