A time-to-event model for the immunogenicity of certolizumab pegol in rheumatoid arthritis subjects
(English)Article in journal (Other academic) Submitted
The advent of biologic therapies improved greatly the treatment of chronic inflammatory diseases. However, these drugs may induce an unwanted specific immune response directed against them. The immunogenicity of biologic drugs is of concern for all healthcare stakeholders and methods for better characterization are needed, as well as means to minimize the occurrence of anti-drug antibodies (ADA). The objective of this analysis was to develop a time-to-event model for characterizing the immunogenicity of certolizumab pegol in subjects suffering from rheumatoid arthritis included in phase II and phase III clinical trials. The time to formation of ADA was analyzed based on previously estimated individual certolizumab pegol concentration-time profiles. In the final model, the hazard of developing ADAs was predicted to depend on time since start of treatment, trough drug concentration in the preceding dosing interval and the concomitant use of methotrexate. Specific study effects were added into the model in order to capture the trends in two studies that remained non-explained after the covariates had been tested. The model may be used to test strategies for minimizing the immunogenicity, such as the use of a loading dose or the reduction of the intervals between dosing.
Research subject Pharmaceutical Science
IdentifiersURN: urn:nbn:se:uu:diva-247893OAI: oai:DiVA.org:uu-247893DiVA: diva2:797902