"Getting the Dose Right"-Revisiting the Topic With Focus on Biologic Agents.

Area of Science:

• Pharmacology
• Immunology
• Drug Development

Background:

• Review of biologic dosing recommendations nearly two decades after Peck and Cross.
• Monoclonal antibodies (MAbs) show mixed clinical success post-approval, particularly in inflammatory diseases and oncology.
• Concomitant use of steroids and immunosuppressants with MAbs complicates treatment and safety profiles.

Purpose of the Study:

• To evaluate the current state of biologic dosing, focusing on monoclonal antibodies.
• To identify persistent challenges and areas for improvement in MAb dosing strategies.
• To explore potential solutions for optimizing MAb therapy, including labeling and monitoring.

Main Methods:

• Review of published literature and clinical experience with biologic dosing.
• Analysis of dosing trends and outcomes for monoclonal antibodies in inflammatory diseases and oncology.
• Assessment of the impact of concomitant medications and anti-drug antibodies (ADAs).

Main Results:

• Overall improvement in biologic dose recommendations, evidenced by fewer drug withdrawals.
• Persistent issues with MAb efficacy and safety in inflammatory diseases due to disease burden changes.
• Potential for overtreatment with MAbs in oncology, leading to increased costs and adverse events.

Conclusions:

• While biologic dosing has improved, challenges remain, particularly with monoclonal antibodies.
• Product labeling should incorporate alternative dosing strategies and therapeutic drug monitoring for dose individualization.
• Further optimization is needed to improve clinical response, reduce anti-drug antibody incidence, and manage treatment costs.