Thiopurines and their optimization during infliximab induction and maintenance: A retrospective study in Crohn's disease.
Azathioprine
/ administration & dosage
Biomarkers
/ blood
Crohn Disease
/ diagnosis
Drug Therapy, Combination
Female
Guanine Nucleotides
/ blood
Humans
Immunosuppressive Agents
/ administration & dosage
Infliximab
/ administration & dosage
Maintenance Chemotherapy
/ methods
Male
Mercaptopurine
/ administration & dosage
Remission Induction
/ methods
Retrospective Studies
Thionucleotides
/ blood
Treatment Outcome
6-Thioguanine nucleotide
Crohn's disease
Inflammatory bowel disease
Infliximab
Thiopurine
Journal
Journal of gastroenterology and hepatology
ISSN: 1440-1746
Titre abrégé: J Gastroenterol Hepatol
Pays: Australia
ID NLM: 8607909
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
revised:
11
08
2020
received:
21
04
2020
accepted:
21
08
2020
pubmed:
4
9
2020
medline:
25
9
2021
entrez:
4
9
2020
Statut:
ppublish
Résumé
Combining therapy with a thiopurine is favored when commencing infliximab in Crohn's disease; however, the optimal 6-thioguanine nucleotide (TGN) level and how long to continue thiopurines after induction are uncertain. We aimed to compare outcomes after induction and during maintenance in combination therapy versus infliximab monotherapy in Crohn's and to examine whether TGN levels were associated with outcomes. Crohn's patients induced with infliximab with or without concomitant thiopurines were retrospectively identified. Response to induction and clinical outcomes in subsequent 6-month maintenance semesters were analyzed. A TGN level ≥235 pmol/8 × 10 In 89 patients, response to induction was higher in combination therapy than monotherapy (74 vs 47%, P = 0.04). This benefit was only seen in patients with a therapeutic TGN (odds ratio 3.72, confidence interval 1.07-13.0, P = 0.04). Combination therapy during induction yielded a three times longer time to subsequent need for treatment escalation or treatment failure compared with monotherapy (29 vs 9 months, P = 0.01), with both therapeutic and subtherapeutic TGNs independent predictors on multivariate analysis. Among 370 semesters, there was no difference in outcomes between combination therapy and monotherapy (P = 0.42), nor when combination semesters were stratified by therapeutic versus subtherapeutic TGN (P = 0.56). In semester 1 only, a significantly higher remission rate was observed with therapeutic compared with subtherapeutic TGN (76% vs 33%, P = 0.02). Combination therapy dosed with an optimized thiopurine was superior to infliximab monotherapy for induction of response, durability of response, and clinical outcomes in the first 6 months following induction. Thereafter, combination therapy yielded no clinical advantage, supporting consideration of thiopurine withdrawal on a case-by-case basis.
Sections du résumé
BACKGROUND AND AIM
OBJECTIVE
Combining therapy with a thiopurine is favored when commencing infliximab in Crohn's disease; however, the optimal 6-thioguanine nucleotide (TGN) level and how long to continue thiopurines after induction are uncertain. We aimed to compare outcomes after induction and during maintenance in combination therapy versus infliximab monotherapy in Crohn's and to examine whether TGN levels were associated with outcomes.
METHODS
METHODS
Crohn's patients induced with infliximab with or without concomitant thiopurines were retrospectively identified. Response to induction and clinical outcomes in subsequent 6-month maintenance semesters were analyzed. A TGN level ≥235 pmol/8 × 10
RESULTS
RESULTS
In 89 patients, response to induction was higher in combination therapy than monotherapy (74 vs 47%, P = 0.04). This benefit was only seen in patients with a therapeutic TGN (odds ratio 3.72, confidence interval 1.07-13.0, P = 0.04). Combination therapy during induction yielded a three times longer time to subsequent need for treatment escalation or treatment failure compared with monotherapy (29 vs 9 months, P = 0.01), with both therapeutic and subtherapeutic TGNs independent predictors on multivariate analysis. Among 370 semesters, there was no difference in outcomes between combination therapy and monotherapy (P = 0.42), nor when combination semesters were stratified by therapeutic versus subtherapeutic TGN (P = 0.56). In semester 1 only, a significantly higher remission rate was observed with therapeutic compared with subtherapeutic TGN (76% vs 33%, P = 0.02).
CONCLUSIONS
CONCLUSIONS
Combination therapy dosed with an optimized thiopurine was superior to infliximab monotherapy for induction of response, durability of response, and clinical outcomes in the first 6 months following induction. Thereafter, combination therapy yielded no clinical advantage, supporting consideration of thiopurine withdrawal on a case-by-case basis.
Substances chimiques
Biomarkers
0
Guanine Nucleotides
0
Immunosuppressive Agents
0
Thionucleotides
0
6-thioguanylic acid
15867-02-4
Infliximab
B72HH48FLU
Mercaptopurine
E7WED276I5
Azathioprine
MRK240IY2L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
990-998Informations de copyright
© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
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