Modeling the Efficacy of Natalizumab in Multiple Sclerosis Patients Who Switch From Every-4-Week Dosing to Extended-Interval Dosing.

Modeling the Efficacy of Natalizumab in Multiple Sclerosis Patients Who Switch From Every-4-Week Dosing to Extended-Interval Dosing. J Clin Pharmacol. 2020 Sep 19;: Authors: Chang I, Muralidharan KK, Campbell N, Ho PR Abstract Natalizumab is approved for multiple sclerosis treatment at a dose of 300 mg every 4 weeks. Extended-interval dosing of natalizumab has been proposed as a strategy to mitigate the risk of progressive multifocal leukoencephalopathy, but the efficacy of extended-interval dosing is not established. Previous models suggesting lower efficacy when initiating natalizumab treatment with extended-interval dosing rather than every-4-week dosing are inconsistent with reports from clinical observations and real-world studies conducted in patient populations switching to extended-interval dosing after a period of receiving natalizumab every 4 weeks. Here, the efficacy of natalizumab extended-interval dosing was modeled specifically in patients switching from every-4-week dosing to extended-interval dosing. Published population pharmacokinetic/pharmacodynamic models were used to simulate the distribution of alpha-4 integrin saturations for different body weight categories and dosing intervals (every 5, 6, 7, 8, 10, or 12 weeks). Generalized estimating equations relating alpha-4 integrin saturation to probability of multiple sclerosis lesion or relapse were derived from RESTORE trial data, which included patients (n = 175) w...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research