Introduction: Infliximab is an effective treatment for inflammatory bowel disease (IBD). Studies differ regarding the influence of body mass index (BMI) on the response to infliximab, with the majority of studies indicating that increased BMI may be associated with a poorer response to Infliximab. However, the pharmacokinetic mechanisms causing this have not yet been reported. Aims: Examine the correlation between BMI/immunosuppressant use with clinical response, trough and post-infusion levels of infliximab, tumour necrosis factor-α(TNF-α) and anti-drug antibodies(ATI), and determine if these factors can predict future response. Methods: We collected serum from 24 patients receiving Infliximab before and 30 minutes following infusion. Clinical parameters were collected retrospectively and prospectively. ELISA measurements of infliximab, TNF-α and ATI were performed. Results: We confirmed that patients with higher infliximab trough levels have a better response rate and that patients with an elevated BMI display a higher rate of loss of response (20%). Patients with a higher BMI had elevated post-infusion levels of infliximab. Additionally, the ratio of IFX/TNF-α trough levels correlated with clinical response to the following infusion. Conclusion: This study confirms that an elevated BMI is associated with a poorer response to infliximab. For the first time, we describe that a higher BMI correlates with higher post-infusion levels, however this does not correlate with a higher rate of response to the drug, suggesting that circulating drug levels do not correlate with tissue levels. Furthermore, in our small cohort of patients, we identified a possible predictive marker of future response to treatment which may be used to guide dose escalation and predict non-response to infliximab.

Scaldaferri, F., D‘ambrosio, D., Holleran, G., Poscia, A., Petito, V., Lopetuso, L., Graziani, C., Laterza, L., Pistone, M. T., Pecere, S., Currò, D., Gaetani, E., Armuzzi, A., Papa, A., Cammarota, G., Gasbarrini, A., Body mass index influences infliximab post-infusion levels and correlates with prospective loss of response to the drug in a cohort of inflammatory bowel disease patients under maintenance therapy with Infliximab, <<PLOS ONE>>, 2017; 12 (10): N/A-N/A. [doi:10.1371/journal.pone.0186575] [http://hdl.handle.net/10807/113228]

Body mass index influences infliximab post-infusion levels and correlates with prospective loss of response to the drug in a cohort of inflammatory bowel disease patients under maintenance therapy with Infliximab

Scaldaferri, Franco;Poscia, Andrea;Petito, Valentina;Lopetuso, Loris;Graziani, Cristina;Laterza, Lucrezia;Pecere, Silvia;Currò, Diego;Gaetani, Eleonora;Armuzzi, Alessandro;Papa, Alfredo;Cammarota, Giovanni;Gasbarrini, Antonio
2017

Abstract

Introduction: Infliximab is an effective treatment for inflammatory bowel disease (IBD). Studies differ regarding the influence of body mass index (BMI) on the response to infliximab, with the majority of studies indicating that increased BMI may be associated with a poorer response to Infliximab. However, the pharmacokinetic mechanisms causing this have not yet been reported. Aims: Examine the correlation between BMI/immunosuppressant use with clinical response, trough and post-infusion levels of infliximab, tumour necrosis factor-α(TNF-α) and anti-drug antibodies(ATI), and determine if these factors can predict future response. Methods: We collected serum from 24 patients receiving Infliximab before and 30 minutes following infusion. Clinical parameters were collected retrospectively and prospectively. ELISA measurements of infliximab, TNF-α and ATI were performed. Results: We confirmed that patients with higher infliximab trough levels have a better response rate and that patients with an elevated BMI display a higher rate of loss of response (20%). Patients with a higher BMI had elevated post-infusion levels of infliximab. Additionally, the ratio of IFX/TNF-α trough levels correlated with clinical response to the following infusion. Conclusion: This study confirms that an elevated BMI is associated with a poorer response to infliximab. For the first time, we describe that a higher BMI correlates with higher post-infusion levels, however this does not correlate with a higher rate of response to the drug, suggesting that circulating drug levels do not correlate with tissue levels. Furthermore, in our small cohort of patients, we identified a possible predictive marker of future response to treatment which may be used to guide dose escalation and predict non-response to infliximab.
Inglese
http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0186575&type=printable
Scaldaferri, F., D‘ambrosio, D., Holleran, G., Poscia, A., Petito, V., Lopetuso, L., Graziani, C., Laterza, L., Pistone, M. T., Pecere, S., Currò, D., Gaetani, E., Armuzzi, A., Papa, A., Cammarota, G., Gasbarrini, A., Body mass index influences infliximab post-infusion levels and correlates with prospective loss of response to the drug in a cohort of inflammatory bowel disease patients under maintenance therapy with Infliximab, <>, 2017; 12 (10): N/A-N/A. [doi:10.1371/journal.pone.0186575] [http://hdl.handle.net/10807/113228]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/113228
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