Concentrations of 6-Thioguanine Nucleotide Correlate With Trough Levels of Infliximab in Patients With Inflammatory Bowel Disease on Combination Therapy

Andres J. Yarur, Maddie J. Kubiliun, Frank Czul, Daniel A Sussman, Maria A. Quintero, Anjali Jain, Katherine A. Drake, Scott I. Hauenstein, Steven Lockton, Amar R Deshpande, Jamie S Barkin, Sharat Singh, Maria T Abreu

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Background & Aims: In patients with inflammatory bowel diseases, the combination of infliximab and thiopurines (such as 6-thioguanine) is more effective treatment than monotherapy. We assessed the correlation between serum levels of 6-thioguanine (6-TGN) and infliximab levels or antibodies to infliximab (ATI). Methods: We performed a cross-sectional study of 72 patients receiving maintenance therapy with infliximab and a thiopurine for inflammatory bowel disease at the Crohn's and Colitis Center of the University of Miami, FL. We collected clinical, endoscopic, and biochemical data, and levels of thiopurine metabolites. The primary outcomes were trough level of infliximab and the presence of ATI. Results: Levels of 6-TGN correlated with those of infliximab (ρ, 0.53; P < .0001). The cut-off point of 6-TGN that best predicted a higher level of infliximab was 125 pmol/8× 10<sup>8</sup> red blood cells (RBCs) (area under receiver operating characteristic, 0.86; P < .001). Patients in the lowest quartile of 6-TGN had infliximab levels that were similar to patients on no thiopurines (4.3 vs 4.8 mcg/mL, respectively; P= .8). An infliximab level of 8.3 mcg/mL or greater was associated with mucosal healing. Only 8 patients (11%) had detectable ATI. Patients with 6-TGN levels less than 125 pmol/8× 10<sup>8</sup> RBCs were significantly more likely to have ATI (odds ratio, 1.3; 95% confidence interval, 2.3-72.5; P < .01). Conclusions: Although 6-TGN levels of greater than 230 pmol/8× 10<sup>8</sup> RBCs have been associated with improved outcomes in patients on monotherapy, a level of 6-thioguanine of 125 pmol/8× 10<sup>8</sup> RBCs or greater may be adequate to achieve therapeutic levels of infliximab. In the long term, this may minimize the toxicity for patients on combination therapy.

Original languageEnglish (US)
Pages (from-to)1118-1124.e3
JournalClinical Gastroenterology and Hepatology
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Inflammatory Bowel Diseases
Thioguanine
Erythrocytes
Therapeutics
Antibodies
6-thioguanylic acid
Infliximab
Colitis
ROC Curve
Cross-Sectional Studies
Odds Ratio
Confidence Intervals
Serum

Keywords

  • Azathioprine
  • Crohn's Disease
  • Drug Levels
  • Mercaptopurine
  • Ulcerative Colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Concentrations of 6-Thioguanine Nucleotide Correlate With Trough Levels of Infliximab in Patients With Inflammatory Bowel Disease on Combination Therapy. / Yarur, Andres J.; Kubiliun, Maddie J.; Czul, Frank; Sussman, Daniel A; Quintero, Maria A.; Jain, Anjali; Drake, Katherine A.; Hauenstein, Scott I.; Lockton, Steven; Deshpande, Amar R; Barkin, Jamie S; Singh, Sharat; Abreu, Maria T.

In: Clinical Gastroenterology and Hepatology, Vol. 13, No. 6, 01.06.2015, p. 1118-1124.e3.

Research output: Contribution to journalArticle

Yarur, Andres J. ; Kubiliun, Maddie J. ; Czul, Frank ; Sussman, Daniel A ; Quintero, Maria A. ; Jain, Anjali ; Drake, Katherine A. ; Hauenstein, Scott I. ; Lockton, Steven ; Deshpande, Amar R ; Barkin, Jamie S ; Singh, Sharat ; Abreu, Maria T. / Concentrations of 6-Thioguanine Nucleotide Correlate With Trough Levels of Infliximab in Patients With Inflammatory Bowel Disease on Combination Therapy. In: Clinical Gastroenterology and Hepatology. 2015 ; Vol. 13, No. 6. pp. 1118-1124.e3.
@article{588f60d99c4e4a1396b34c448d1cf653,
title = "Concentrations of 6-Thioguanine Nucleotide Correlate With Trough Levels of Infliximab in Patients With Inflammatory Bowel Disease on Combination Therapy",
abstract = "Background & Aims: In patients with inflammatory bowel diseases, the combination of infliximab and thiopurines (such as 6-thioguanine) is more effective treatment than monotherapy. We assessed the correlation between serum levels of 6-thioguanine (6-TGN) and infliximab levels or antibodies to infliximab (ATI). Methods: We performed a cross-sectional study of 72 patients receiving maintenance therapy with infliximab and a thiopurine for inflammatory bowel disease at the Crohn's and Colitis Center of the University of Miami, FL. We collected clinical, endoscopic, and biochemical data, and levels of thiopurine metabolites. The primary outcomes were trough level of infliximab and the presence of ATI. Results: Levels of 6-TGN correlated with those of infliximab (ρ, 0.53; P < .0001). The cut-off point of 6-TGN that best predicted a higher level of infliximab was 125 pmol/8× 108 red blood cells (RBCs) (area under receiver operating characteristic, 0.86; P < .001). Patients in the lowest quartile of 6-TGN had infliximab levels that were similar to patients on no thiopurines (4.3 vs 4.8 mcg/mL, respectively; P= .8). An infliximab level of 8.3 mcg/mL or greater was associated with mucosal healing. Only 8 patients (11{\%}) had detectable ATI. Patients with 6-TGN levels less than 125 pmol/8× 108 RBCs were significantly more likely to have ATI (odds ratio, 1.3; 95{\%} confidence interval, 2.3-72.5; P < .01). Conclusions: Although 6-TGN levels of greater than 230 pmol/8× 108 RBCs have been associated with improved outcomes in patients on monotherapy, a level of 6-thioguanine of 125 pmol/8× 108 RBCs or greater may be adequate to achieve therapeutic levels of infliximab. In the long term, this may minimize the toxicity for patients on combination therapy.",
keywords = "Azathioprine, Crohn's Disease, Drug Levels, Mercaptopurine, Ulcerative Colitis",
author = "Yarur, {Andres J.} and Kubiliun, {Maddie J.} and Frank Czul and Sussman, {Daniel A} and Quintero, {Maria A.} and Anjali Jain and Drake, {Katherine A.} and Hauenstein, {Scott I.} and Steven Lockton and Deshpande, {Amar R} and Barkin, {Jamie S} and Sharat Singh and Abreu, {Maria T}",
year = "2015",
month = "6",
day = "1",
doi = "10.1016/j.cgh.2014.12.026",
language = "English (US)",
volume = "13",
pages = "1118--1124.e3",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "6",

}

TY - JOUR

T1 - Concentrations of 6-Thioguanine Nucleotide Correlate With Trough Levels of Infliximab in Patients With Inflammatory Bowel Disease on Combination Therapy

AU - Yarur, Andres J.

AU - Kubiliun, Maddie J.

AU - Czul, Frank

AU - Sussman, Daniel A

AU - Quintero, Maria A.

AU - Jain, Anjali

AU - Drake, Katherine A.

AU - Hauenstein, Scott I.

AU - Lockton, Steven

AU - Deshpande, Amar R

AU - Barkin, Jamie S

AU - Singh, Sharat

AU - Abreu, Maria T

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Background & Aims: In patients with inflammatory bowel diseases, the combination of infliximab and thiopurines (such as 6-thioguanine) is more effective treatment than monotherapy. We assessed the correlation between serum levels of 6-thioguanine (6-TGN) and infliximab levels or antibodies to infliximab (ATI). Methods: We performed a cross-sectional study of 72 patients receiving maintenance therapy with infliximab and a thiopurine for inflammatory bowel disease at the Crohn's and Colitis Center of the University of Miami, FL. We collected clinical, endoscopic, and biochemical data, and levels of thiopurine metabolites. The primary outcomes were trough level of infliximab and the presence of ATI. Results: Levels of 6-TGN correlated with those of infliximab (ρ, 0.53; P < .0001). The cut-off point of 6-TGN that best predicted a higher level of infliximab was 125 pmol/8× 108 red blood cells (RBCs) (area under receiver operating characteristic, 0.86; P < .001). Patients in the lowest quartile of 6-TGN had infliximab levels that were similar to patients on no thiopurines (4.3 vs 4.8 mcg/mL, respectively; P= .8). An infliximab level of 8.3 mcg/mL or greater was associated with mucosal healing. Only 8 patients (11%) had detectable ATI. Patients with 6-TGN levels less than 125 pmol/8× 108 RBCs were significantly more likely to have ATI (odds ratio, 1.3; 95% confidence interval, 2.3-72.5; P < .01). Conclusions: Although 6-TGN levels of greater than 230 pmol/8× 108 RBCs have been associated with improved outcomes in patients on monotherapy, a level of 6-thioguanine of 125 pmol/8× 108 RBCs or greater may be adequate to achieve therapeutic levels of infliximab. In the long term, this may minimize the toxicity for patients on combination therapy.

AB - Background & Aims: In patients with inflammatory bowel diseases, the combination of infliximab and thiopurines (such as 6-thioguanine) is more effective treatment than monotherapy. We assessed the correlation between serum levels of 6-thioguanine (6-TGN) and infliximab levels or antibodies to infliximab (ATI). Methods: We performed a cross-sectional study of 72 patients receiving maintenance therapy with infliximab and a thiopurine for inflammatory bowel disease at the Crohn's and Colitis Center of the University of Miami, FL. We collected clinical, endoscopic, and biochemical data, and levels of thiopurine metabolites. The primary outcomes were trough level of infliximab and the presence of ATI. Results: Levels of 6-TGN correlated with those of infliximab (ρ, 0.53; P < .0001). The cut-off point of 6-TGN that best predicted a higher level of infliximab was 125 pmol/8× 108 red blood cells (RBCs) (area under receiver operating characteristic, 0.86; P < .001). Patients in the lowest quartile of 6-TGN had infliximab levels that were similar to patients on no thiopurines (4.3 vs 4.8 mcg/mL, respectively; P= .8). An infliximab level of 8.3 mcg/mL or greater was associated with mucosal healing. Only 8 patients (11%) had detectable ATI. Patients with 6-TGN levels less than 125 pmol/8× 108 RBCs were significantly more likely to have ATI (odds ratio, 1.3; 95% confidence interval, 2.3-72.5; P < .01). Conclusions: Although 6-TGN levels of greater than 230 pmol/8× 108 RBCs have been associated with improved outcomes in patients on monotherapy, a level of 6-thioguanine of 125 pmol/8× 108 RBCs or greater may be adequate to achieve therapeutic levels of infliximab. In the long term, this may minimize the toxicity for patients on combination therapy.

KW - Azathioprine

KW - Crohn's Disease

KW - Drug Levels

KW - Mercaptopurine

KW - Ulcerative Colitis

UR - http://www.scopus.com/inward/record.url?scp=84928628450&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928628450&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2014.12.026

DO - 10.1016/j.cgh.2014.12.026

M3 - Article

VL - 13

SP - 1118-1124.e3

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 6

ER -