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

被引：0

作者：

Yu, Natalie ^{[1
]}

Lee, Tanya ^{[1
]}

Tassone, Daniel ^{[1
]}

Vogrin, Sara ^{[2
]}

Phan, Steven ^{[3
]}

Wu, Damien M. ^{[3
]}

Zhang, Jason ^{[4
,5
]}

Wang, Luke ^{[6
]}

Tjahyadi, Jason ^{[7
]}

Dutt, Krishneel ^{[7
]}

Liou, Hana ^{[9
]}

Basnayake, Chamara ^{[1
,2
]}

Wright, Emily ^{[1
,2
]}

Niewiadomski, Ola ^{[1
]}

Lust, Mark ^{[1
]}

Schulberg, Julien ^{[1
,2
]}

Kamm, Michael A. ^{[1
,2
]}

Connell, William ^{[1
,2
]}

Thompson, Alexander J. ^{[1
,2
]}

Hilmi, Ida ^{[10
]}

Ali, Raja A. Raja ^{[11
]}

Wei, Shu C. ^{[9
]}

De Cruz, Peter ^{[2
,3
]}

Friedman, Antony B. ^{[4
,5
]}

Moore, Gregory T. ^{[6
,8
]}

Van Langenberg, Daniel ^{[7
,8
]}

Ding, Nik S. ^{[1
,2
]}

机构：

[1] St Vincents Hosp Melbourne, Dept Gastroenterol, 41 Victoria Parade, Melbourne, Vic 3065, Australia

[2] Univ Melbourne, Dept Med, Melbourne, Vic, Australia

[3] Austin Hlth, Dept Gastroenterol, Melbourne, Vic, Australia

[4] Alfred Hlth, Dept Gastroenterol, Melbourne, Vic, Australia

[5] Monash Univ, Melbourne, Vic, Australia

[6] Monash Hlth, Dept Gastroenterol, Melbourne, Vic, Australia

[7] Eastern Hlth, Dept Gastroenterol, Melbourne, Vic, Australia

[8] Monash Univ, Dept Med, Melbourne, Vic, Australia

[9] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan

[10] Univ Malaya, Med Ctr, Dept Med, Kuala Lumpur, Malaysia

[11] Hosp Univ Kebangsaan Malaysia, Dept Med, Kuala Lumpur, Malaysia

来源：

INTERNAL MEDICINE JOURNAL | 2024年 / 54卷 / 11期

关键词：

inflammatory bowel disease; therapeutic drug monitoring; thiopurines; infliximab; adalimumab; NONMELANOMA SKIN-CANCER; ANTI-TNF THERAPY; CROHNS-DISEASE; ULCERATIVE-COLITIS; TROUGH LEVELS; RISK; AZATHIOPRINE; MONOTHERAPY; THIOPURINES; IMMUNOMODULATOR;

D O I：

10.1111/imj.16504

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1856 / 1866

页数：11

共 38 条

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