ECTRIMS eLearning

Pharmacodynamics and pharmacokinetics of Natalizumab administered at Extended Interval Dosing
ECTRIMS Learn. Zhovtis Ryerson L. 10/25/17; 199762; EP1742
Dr. Lana Zhovtis Ryerson
Dr. Lana Zhovtis Ryerson
Contributions
Abstract

Abstract: EP1742

Type: ePoster

Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments

Objective: To evaluate α4β1 integrin saturations (SAT) and serum concentrations (CONC) in patients on extended interval regiments of Natalizumab (NTZ).
Background: NTZ is approved for every 4-week administration as effective therapy for multiple sclerosis (MS), but carries risk of progressive multifocal leukoencephalopathy (PML). Extended interval dosing (EID) is being explored in attempt to decrease PML risk. Pharmacodynamics and pharmacokinetics of NTZ at EID are unknown.
Methods: Patients who consistently received NTZ on every 6 week EID schedule (EID-6) or every 8 EID schedule (EID-8) for 12 months or more were included. Peak and trough NTZ CONC and SAT were measured using ELISA (Covance) and flow cytometric analysis of whole blood (LabCorp), respectively. Chart review was performed to evaluate disease status.
Results: 28 patients were enrolled, of whom 17 were women. Mean age ±SD (range) 42.2±11.5 (20-64). Peak CONC EID-6 121.5±33.3 (82.6-203.0) and EID-8 114.3±24.1 (78.9-145.0) (p= 0.53). Trough CONC EID-6 14.0±8.9 (0.5-28.8) and EID-8 6.1±7.1 (0.5-22.9) (p = 0.02). In EID-6, 55% achieved 'high' CONC (defined as >10µg/mL); 39% 'adequate' CONC (defined as 2-10 µg/mL); and 8% 'inadequate' CONC (defined as < 2 µg/mL). In EID-8, 21% achieved 'high' CONC, 38% 'adequate' CONC; and 43% 'inadequate' CONC. Peak SAT EID-6 91.4±4.3 (83.8-96.0) and EID-8 92.7±4.9 (83.7-93.9) (p=0.69). Trough SAT EID-6 was 72.1±11.1 (45.7-87.6) and EID-8 55.0±24.2(4.5-87.7) (p= 0.02). In EID-6, 29% achieved 'high' SAT (defined as >80%); 64% 'adequate' SAT (defined as 50-80%); 7% 'inadequate' SAT (defined as < 50%). In EID-8 group, 7% achieved 'high' SAT; 57% 'adequate' SAT; 36% 'inadequate' SAT.
Conclusions: Majority of patients on NTZ EID maintained adequate CONC and SAT through increasing dose interval resulted in higher number of patients with “inadequate” CONC/SAT. Analyses of the relationship between NTZ CONC, SAT, and clinical outcomes is planned. This will help understand which CONC/SAT of NTZ is sufficient to exclude entry of auto-reactive T cells into CNS and thereby achieving clinically meaningful response.
Disclosure: Source of funding: Biogen as Investigator Initiated Trial
Zhovtis Ryerson L: has serves on scientific advisory board for Biogen, has received compensation for participation in speaker bureau for Biogen, Teva. and has received research support from Biogen.
Zuniga Estrada G: nothing to disclose
Jacob A: nothing to disclose
Bacon T: nothing to disclose
Pandey K: has received speaker and consulting fees from Acorda, Teva, and Biogen
Mohn J: nothing to disclose
Kister I: has served on scientific advisory board for Biogen and Genentech. Received research support from Guthy-Jackson Charitable Foundation, National Multiple Sclerosis Society, Biogen, Serono, and Novartis.

Abstract: EP1742

Type: ePoster

Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments

Objective: To evaluate α4β1 integrin saturations (SAT) and serum concentrations (CONC) in patients on extended interval regiments of Natalizumab (NTZ).
Background: NTZ is approved for every 4-week administration as effective therapy for multiple sclerosis (MS), but carries risk of progressive multifocal leukoencephalopathy (PML). Extended interval dosing (EID) is being explored in attempt to decrease PML risk. Pharmacodynamics and pharmacokinetics of NTZ at EID are unknown.
Methods: Patients who consistently received NTZ on every 6 week EID schedule (EID-6) or every 8 EID schedule (EID-8) for 12 months or more were included. Peak and trough NTZ CONC and SAT were measured using ELISA (Covance) and flow cytometric analysis of whole blood (LabCorp), respectively. Chart review was performed to evaluate disease status.
Results: 28 patients were enrolled, of whom 17 were women. Mean age ±SD (range) 42.2±11.5 (20-64). Peak CONC EID-6 121.5±33.3 (82.6-203.0) and EID-8 114.3±24.1 (78.9-145.0) (p= 0.53). Trough CONC EID-6 14.0±8.9 (0.5-28.8) and EID-8 6.1±7.1 (0.5-22.9) (p = 0.02). In EID-6, 55% achieved 'high' CONC (defined as >10µg/mL); 39% 'adequate' CONC (defined as 2-10 µg/mL); and 8% 'inadequate' CONC (defined as < 2 µg/mL). In EID-8, 21% achieved 'high' CONC, 38% 'adequate' CONC; and 43% 'inadequate' CONC. Peak SAT EID-6 91.4±4.3 (83.8-96.0) and EID-8 92.7±4.9 (83.7-93.9) (p=0.69). Trough SAT EID-6 was 72.1±11.1 (45.7-87.6) and EID-8 55.0±24.2(4.5-87.7) (p= 0.02). In EID-6, 29% achieved 'high' SAT (defined as >80%); 64% 'adequate' SAT (defined as 50-80%); 7% 'inadequate' SAT (defined as < 50%). In EID-8 group, 7% achieved 'high' SAT; 57% 'adequate' SAT; 36% 'inadequate' SAT.
Conclusions: Majority of patients on NTZ EID maintained adequate CONC and SAT through increasing dose interval resulted in higher number of patients with “inadequate” CONC/SAT. Analyses of the relationship between NTZ CONC, SAT, and clinical outcomes is planned. This will help understand which CONC/SAT of NTZ is sufficient to exclude entry of auto-reactive T cells into CNS and thereby achieving clinically meaningful response.
Disclosure: Source of funding: Biogen as Investigator Initiated Trial
Zhovtis Ryerson L: has serves on scientific advisory board for Biogen, has received compensation for participation in speaker bureau for Biogen, Teva. and has received research support from Biogen.
Zuniga Estrada G: nothing to disclose
Jacob A: nothing to disclose
Bacon T: nothing to disclose
Pandey K: has received speaker and consulting fees from Acorda, Teva, and Biogen
Mohn J: nothing to disclose
Kister I: has served on scientific advisory board for Biogen and Genentech. Received research support from Guthy-Jackson Charitable Foundation, National Multiple Sclerosis Society, Biogen, Serono, and Novartis.

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies