Yu, Natalie and Lee, Tanya and Tassone, Daniel and Vogrin, Sara and Phan, Steven and Wu, Damien M. and Zhang, Jason and Wang, Luke and Tjahyadi, Jason and Dutt, Krishneel and Liou, Hana and Basnayake, Chamara and Wright, Emily and Niewiadomski, Ola and Lust, Mark and Schulberg, Julien and Kamm, Michael A. and Connell, William and Thompson, Alexander J. and Hilmi, Ida and Ali, Raja A. Raja and Wei, Shu C. and De Cruz, Peter and Friedman, Antony B. and Moore, Gregory T. and Van Langenberg, Daniel and Ding, Nik S. (2024) 6-Thioguanine nucleotide levels are associated with infliximab but not adalimumab levels in inflammatory bowel disease patients on combination therapy. Internal Medicine Journal, 54 (11). pp. 1856-1866. ISSN 1444-0903, DOI https://doi.org/10.1111/imj.16504.
Full text not available from this repository.Abstract
BackgroundThiopurine co-therapy with anti-tumour necrosis factor-alpha (anti-TNF alpha) agents is associated with higher anti-TNF alpha drug levels and reduced immunogenicity in inflammatory bowel disease (IBD).AimsWe aimed to evaluate the association between 6-thioguanine nucleotide (6-TGN) and anti-TNF alpha levels and the optimal 6-TGN threshold level associated with higher anti-TNF alpha levels in combination therapy.MethodsWe performed a retrospective cross-sectional multicentre study of patients with IBD on combination anti-TNF alpha and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti-TNF alpha levels. Receiver operator characteristic curves were used to define the optimal 6-TGN cut-off levels associated with therapeutic anti-TNF alpha levels.ResultsThe study included 743 paired 6-TGN and anti-TNF alpha levels (640 infliximab and 103 adalimumab). 6-TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6-TGN cut-off associated with therapeutic infliximab levels (>= 5 mcg/mL) was 261 pmol/8 x 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 x 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (>= 7.5 mcg/mL), the 6-TGN cut-off was 218.5 pmol/8 x 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 x 108 RBC (AUC = 0.63) for escalated dosing.Conclusion6-TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6-TGN levels in the lower end of the therapeutic range (230-260 pmol/8 x 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | inflammatory bowel disease; therapeutic drug monitoring; thiopurines; infliximab; adalimumab |
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Universiti Malaya Medical Centre (UMMC) |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 13 Feb 2025 01:56 |
| Last Modified: | 13 Feb 2025 01:56 |
| URI: | http://eprints.um.edu.my/id/eprint/47466 |
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