Session Information
Date: Sunday, November 8, 2015
Session Title: Vasculitis Poster I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: The thiopurine azathioprine (AZA) is an inactive pro-drug that
undergoes complex metabolic transformations leading to the formation of
6-thioguanine nucleotide (6-TGN), the active metabolite, and
6-methylmercaptopurine (6-MMP), an inactive and potentially hepatotoxic
metabolite (Figure). Evidence in inflammatory bowel disease (IBD) suggests that
there is a weak correlation between the thiopurine dose and the 6-TGN blood
concentration. In a subgroup of patients, production of 6-MMP predominates over
production of active 6-TGN. This phenomenon is called hypermethylation. These
patients are identified as shunters and are known to be thiopurine resistant
unless combined with allopurinol. Current data in IBD support the clinical
usefulness of 6-TGN and 6-MMP monitoring to improve the effectiveness and the
safety profile of thiopurines. There are few data regarding the clinical
benefits of thiopurine metabolites monitoring in patients with rheumatic diseases.
The aims of the study were to evaluate the thiopurine doses used to treat diseases
other than IBD, to estimate the correlation between the thiopurine dose and the
6-TGN blood concentration, to identify shunters and to describe their
management.
Methods: Patients were identified using the central laboratory database and
data were retrospectively collected. Spearman’s correlation coefficient was
used to estimate the correlation between the thiopurine dose (mg/kg) and the
blood concentration of 6-TGN (pmol/8×108 erythrocytes).
Results: Seventy-one patients were
included. Twenty-nine patients (41%) received AZA for vasculitis, 26 (37%) for
connective tissue disease, 9 (13%) for myositis, and 7 (10%) for various
conditions. Correlation between the thiopurine dose (mg/kg) and the blood concentration
of 6-TGN has been estimated at the first thiopurine metabolites assay and at
the greatest dose of thiopurine. Spearman’s correlation coefficients are 0.337
(p=0.004) and 0.270 (p=0.023), respectively. For the subgroup of non-shunters,
the correlation was consistent with that observed for
the overall patient sample with Spearman’s correlation coefficients of 0.319
(p=0,026) and 0.399 (p=0.005), respectively. Twenty-two
patients (31%) were identified as shunters and 6 of them developed significant
aminotransferase elevations (>1.5 times the normal upper limit). The
AZA-allopurinol combination therapy was used in 9 shunters and allowed a shift
toward 6-TGN production in 8 of them.
Conclusion: In this retrospective study, the correlation between the thiopurine
dose and the 6-TGN blood concentration was weak. Thirty-one percent of the patients
were identified as shunters. Consequently, thiopurine
metabolites monitoring demonstrated its clinical
usefulness and it should be routinely used to guide thiopurine therapy in
patients treated for rheumatic diseases.
To cite this abstract in AMA style:
Chapdelaine A, Doré M, Troyanov Y, Mansour AM. Evaluation of Thiopurine Metabolites Monitoring in Patients Treated with Azathioprine for Rheumatic Diseases [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/evaluation-of-thiopurine-metabolites-monitoring-in-patients-treated-with-azathioprine-for-rheumatic-diseases/. Accessed February 25, 2021.« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/evaluation-of-thiopurine-metabolites-monitoring-in-patients-treated-with-azathioprine-for-rheumatic-diseases/