Dataset Information

Randomised clinical trial: individualised vs. weight-based dosing of azathioprine in Crohn's disease.

ABSTRACT:

Background

Azathioprine (AZA), a pro-drug metabolised to the active metabolites 6-tioguanine nucleotides (6TGN), is a steroid-sparing therapy for Crohn's disease (CD).

Aim

To investigate whether AZA therapy is optimised by individualised dosing based on thiopurine methyltransferase (TPMT) activity and 6TGN concentrations.

Methods

This multicentre, double-blind, randomised controlled trial compared the efficacy and safety of weight-based vs. individualised AZA dosing in inducing and maintaining remission in adults and children with steroid-treated CD. The primary outcome was clinical remission (CR) at 16 weeks. In the weight-based arm, subjects received 2.5 mg/kg/day. In the individualised dosing arm, the initial AZA dose was 1.0 mg/kg/day (if intermediate TPMT) or 2.5 mg/kg/day (if normal TPMT). Starting at week 5, the dose was adjusted to target 6TGN concentrations of 250-400 pmol/8 × 10(8) red blood cells (RBC), or to a maximal dose of 4 mg/kg/day.

Results

After randomising 50 subjects, the trial was stopped prematurely due to insufficient enrolment. In intention-to-treat analysis, CR rates at week 16 were 40% in the individualised arm vs. 16% in the weight-based arm (P = 0.11). In per-protocol (PP) analysis, week 16 CR rates were 60% in the individualised arm and 25% in the weight-based arm (P = 0.12). At week 16, median 6TGN concentrations in PP remitters and nonremitters were 216 and 149 pmol/8 × 10(8) RBC respectively (P = 0.07).

Conclusions

Despite trends favouring individualised over weight-based AZA dosing, there were no statistically significant differences in efficacy, likely due to low statistical power and inability to achieve the target 6TGN concentrations in the individualised arm. [Clinicaltrials.Gov Identifier Nct00113503].

SUBMITTER: Dassopoulos T

PROVIDER: S-EPMC3918445 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Publications

Randomised clinical trial: individualised vs. weight-based dosing of azathioprine in Crohn's disease.

Dassopoulos T T Dubinsky M C MC Bentsen J L JL Martin C F CF Galanko J A JA Seidman E G EG Sandler R S RS Hanauer S B SB

Alimentary pharmacology & therapeutics 20131117 2

<h4>Background</h4>Azathioprine (AZA), a pro-drug metabolised to the active metabolites 6-tioguanine nucleotides (6TGN), is a steroid-sparing therapy for Crohn's disease (CD).<h4>Aim</h4>To investigate whether AZA therapy is optimised by individualised dosing based on thiopurine methyltransferase (TPMT) activity and 6TGN concentrations.<h4>Methods</h4>This multicentre, double-blind, randomised controlled trial compared the efficacy and safety of weight-based vs. individualised AZA dosing in indu ...[more]

PMID: 24237037

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Project description:AimTo determine the risk factors of nonadherence to azathioprine (AZA) maintenance therapy for Crohn's disease (CD) and to evaluate the influence of patients' educational program on adherence to AZA maintenance therapy.MethodsPatients receiving AZA as maintenance therapy for CD were enrolled. Demographic data, clinical data, and usage information were collected. Univariate and multivariate analyses were performed to identify the risk factors of nonadherence. Then, patients' educational program was conducted. One year after the program, the improvements in adherence and relapse rates were compared between educational and noneducational groups.ResultsA total of 378 CD patients receiving AZA as maintenance therapy were enrolled from September 2008 to September 2018. Nonadherence occurred in 43.9% (166/378) of patients. Univariate analysis revealed that young age, education, alcoholism, anxiety, depression, concern belief, and lack of necessity belief and AZA knowledge were risk factors of nonadherence (P < 0.05). Multivariate logistic regression showed that anxiety (OR 6.244, 95% CI 2.563-15.213), depression (OR 3.801, 95% CI 1.281-11.278), and concern belief (OR 19.531, 95% CI 3.393-120.732) were independent risk factors of nonadherence. Necessity belief (OR 0.961, 95% CI 0.925-0.999) and AZA knowledge (OR 0.823, 95% CI 0.758-0.903) were protective factors of adherence. One year after the AZA educational program, the necessity belief, AZA knowledge, and adherence of the educational group significantly improved (P < 0.05). Concern belief was significantly lower in the educational group than that in the noneducational group (P < 0.05). Moreover, the noneducational group suffered significantly higher endoscopic relapse rates than that the educational group (15.9% vs. 30.1%, P = 0.035).ConclusionsNonadherence occurred frequently in CD patients receiving AZA maintenance therapy. Educational programs could improve patients' adherence mainly by promoting their beliefs and knowledge of AZA and could reduce relapse rates during treatment.

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Dataset Information

Randomised clinical trial: individualised vs. weight-based dosing of azathioprine in Crohn's disease.

Background

Aim

Methods

Results

Conclusions

Publications

Randomised clinical trial: individualised vs. weight-based dosing of azathioprine in Crohn's disease.

Similar Datasets

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