6-Thioguanine nucleotide levels are associated with infliximab but not adalimumab levels in inflammatory bowel disease patients on combination therapy.

adalimumab inflammatory bowel disease infliximab therapeutic drug monitoring thiopurines

Journal

Internal medicine journal
ISSN: 1445-5994
Titre abrégé: Intern Med J
Pays: Australia
ID NLM: 101092952

Informations de publication

Date de publication:
05 Sep 2024
Historique:
received: 10 04 2024
accepted: 31 07 2024
medline: 5 9 2024
pubmed: 5 9 2024
entrez: 5 9 2024
Statut: aheadofprint

Résumé

Thiopurine co-therapy with anti-tumour necrosis factor-alpha (anti-TNFα) agents is associated with higher anti-TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD). We aimed to evaluate the association between 6-thioguanine nucleotide (6-TGN) and anti-TNFα levels and the optimal 6-TGN threshold level associated with higher anti-TNFα levels in combination therapy. We performed a retrospective cross-sectional multicentre study of patients with IBD on combination anti-TNFα 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-TNFα levels. Receiver operator characteristic curves were used to define the optimal 6-TGN cut-off levels associated with therapeutic anti-TNFα levels. The study included 743 paired 6-TGN and anti-TNFα 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 × 10 6-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 × 10

Sections du résumé

BACKGROUND BACKGROUND
Thiopurine co-therapy with anti-tumour necrosis factor-alpha (anti-TNFα) agents is associated with higher anti-TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD).
AIMS OBJECTIVE
We aimed to evaluate the association between 6-thioguanine nucleotide (6-TGN) and anti-TNFα levels and the optimal 6-TGN threshold level associated with higher anti-TNFα levels in combination therapy.
METHODS METHODS
We performed a retrospective cross-sectional multicentre study of patients with IBD on combination anti-TNFα 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-TNFα levels. Receiver operator characteristic curves were used to define the optimal 6-TGN cut-off levels associated with therapeutic anti-TNFα levels.
RESULTS RESULTS
The study included 743 paired 6-TGN and anti-TNFα 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 × 10
CONCLUSION CONCLUSIONS
6-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 × 10

Identifiants

pubmed: 39234975
doi: 10.1111/imj.16504
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024 Royal Australasian College of Physicians.

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Auteurs

Natalie Yu (N)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.

Tanya Lee (T)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.

Daniel Tassone (D)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.

Sara Vogrin (S)

Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.

Steven Phan (S)

Department of Gastroenterology, Austin Health, Melbourne, Victoria, Australia.

Damien M Wu (DM)

Department of Gastroenterology, Austin Health, Melbourne, Victoria, Australia.

Jason Zhang (J)

Department of Gastroenterology, Alfred Health and Monash University, Melbourne, Victoria, Australia.

Luke Wang (L)

Department of Gastroenterology, Monash Health, Melbourne, Victoria, Australia.

Jason Tjahyadi (J)

Department of Gastroenterology, Eastern Health, Melbourne, Victoria, Australia.

Krishneel Dutt (K)

Department of Gastroenterology, Eastern Health, Melbourne, Victoria, Australia.

Hana Liou (H)

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Chamara Basnayake (C)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.

Emily Wright (E)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.

Ola Niewiadomski (O)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.

Mark Lust (M)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.

Julien Schulberg (J)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.

Michael A Kamm (MA)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.

William Connell (W)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.

Alexander J Thompson (AJ)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.

Ida Hilmi (I)

Department of Medicine, University of Malaya Medical Centre, Kuala Lumpur, Malaysia.

Raja A Raja Ali (RA)

Department of Medicine, Hospital Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

Shu C Wei (SC)

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Peter De Cruz (P)

Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
Department of Gastroenterology, Austin Health, Melbourne, Victoria, Australia.

Antony B Friedman (AB)

Department of Gastroenterology, Alfred Health and Monash University, Melbourne, Victoria, Australia.

Gregory T Moore (GT)

Department of Gastroenterology, Monash Health, Melbourne, Victoria, Australia.
Department of Medicine, Monash University, Melbourne, Victoria, Australia.

Daniel Van Langenberg (D)

Department of Gastroenterology, Eastern Health, Melbourne, Victoria, Australia.
Department of Medicine, Monash University, Melbourne, Victoria, Australia.

Nik S Ding (NS)

Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.

Classifications MeSH