Antidrug antibodies (ADAs) are commonly found in healthy subjects after a single intravenous dose of infliximab and result in faster clearance of infliximab, shorter elimination time, and lower serum infliximab levels, according to a study published in the September 2017 issue of Drugs in R&D by Eli D. Ehrenpreis, MD.
Antidrug antibodies (ADAs) are commonly found in healthy subjects after a single intravenous dose of infliximab and result in faster clearance of infliximab, shorter elimination time, and lower serum infliximab levels, according to a study published in the September 2017 issue of Drugs in R&D by Eli D. Ehrenpreis, MD.
ADAs to infliximab developed in 37% of healthy subjects, and clearance of infliximab is more rapid, elimination half-lives shorter, and trough levels decreased in subjects with ADAs. The study is the first to detail the pharmacokinetic (PK) effects of ADAs following a single dose of intravenous infliximab in a group of healthy subjects, and it shows that development of ADAs has the profound effect of increasing drug clearance following the first dose of biologic therapy.
The study obtained data from a single-blind, parallel-group, single-dose study of healthy subjects in 3 treatment groups: SB2 (an infliximab biosimilar), European Union-sourced Remicade (EU-IFX), and US-sourced Remicade (US-IFX). In the study, 159 subjects received 5 mg per kg of intravenous SB2, EU-IFX, or US-IFX for 120 minutes on study day 1, and were followed for 10 weeks for safety, PK, and immunogenicity measurements. Intravenous hydrocortisone, oral acetaminophen, and oral loratadine were given prior to the infusion.
Serum infliximab levels were measured at 1, 2, 3, 6, 12, 24, 48, and 72 hours and at 5, 7, 14, 21, 28, 42, 56, and 70 days after administration. Samples were collected to monitor ADA and neutralizing antibodies (Nabs) at pre-dose and 28 and 70 days after dosing. Data from the first 10 subjects randomized to each treatment arm constituted the group of 30 subjects examined in the study.
The study demonstrates that the presence of ADAs in this population profoundly increases infliximab clearance. “This finding has implications related to the administration of both infliximab and other biologic therapies,” the author concludes. “Since the development of infliximab ADAs probably begins at the time of the first injection and evolves during its presence in circulation, it is likely that an even higher rate of ADA formation is prevented by premedication with intravenous hydrocortisone.”
Further clinical studies will be required to interpret the significance of rapid ADA development to biologic therapy, and strategies for early intervention to prevent this occurrence may be warranted.
Breaking Down Biosimilar Barriers: Payer and PBM Policies
November 13th 2024Part 2 of this series for Global Biosimilars Week dives into the complexities of payer and pharmacy benefit manager (PBM) policies, how they impact biosimilar accessibility, and how addressing these issues may look under a second Trump term.
Biosimilars in America: Overcoming Barriers and Maximizing Impact
July 21st 2024Join us as we explore the complexities of the US biosimilars market, discussing legislative influences, payer and provider adoption factors, and strategies to overcome industry challenges with expert insights from Kyle Noonan, PharmD, MS, value & access strategy manager at Cencora.
Panelists Stress Stakeholder Education to Build Confidence in Biosimilars
October 31st 2024By expanding educational initiatives to clarify biosimilar safety, efficacy, and interchangeability, stakeholders can foster trust, improve access, and ensure that biosimilars are widely accepted as high-quality, cost-effective alternatives to originator biologics.
What AmerisourceBergen's Report Reveals About Payers, Biosimilar Pricing Trends
May 28th 2023On this episode of Not So Different, Tasmina Hydery and Brian Biehn from AmerisourceBergen discussed results from a recent survey, that were also presented at Asembia 2023, diving into the payer perspective on biosimilars and current pricing trends across the US biosimilar industry.
Sandoz Report: A Unified Approach to Overcoming Drug Shortages
October 10th 2024A report from Sandoz emphasizes the need for collaboration among stakeholders to eliminate drug shortages impacting over 90% of hospital systems in the US, recommending policy changes and actions to address the ongoing issue, which has caused treatment delays and increased costs.