The Frequency of Thiopurine Methyltransferase Polymorphism in Systemic Lupus Erythematosus SLE

NCT07012239 | Completed FDA Drug

• 1 other identifier: BSMMU/2016
• Study Type: observational
• Target: 348
• Locations: 1 country
• Sites: 1

Brief Summary

ABSTRACT Background: Thiopurine S-methyltransferase (TPMT) is the rate-limiting enzyme for azathioprine (AZA) metabolism. Polymorphisms of this gene induce adverse effects of AZA. AZA is widely used as an immunosuppressant agent for the remission maintenance of Systemic Lupus Erythematosus (SLE). Objective: To study the frequency of TPMT polymorphism in SLE patients. Methods and Materials: This observational nested case control study was conducted in the department of Rheumatology (BMU) and Pharmacokinetics and Pharmacogenetics Laboratory, department of Pharmacy, Dhaka University (DU), Dhaka, from July 2014 to January 2016. 348 (aged 18-65 years) SLE patients were enrolled, 11 were excluded, and 337 were included. Among them, 120 patients took AZA. All patients gave informed written consent. We included the patient who fulfilled ACR criteria for SLE and excluded the following patients: pregnant woman, taking another myelosuppressive or experimental drug, recent blood transfusion, and unwilling patient. A five ml blood sample was collected from each patient and analyzed for a genetic study. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the gene. The individual patient's disease activity was evaluated using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The chi-square test was used to compare the frequency of alleles in SEE patients who received AZA. Results: A total of 348 SLE patients accepted the request to participate. DNA was not isolated from 11 patients, and they were excluded from this study. The remaining 337 patients were evaluated. The patients were divided into two groups: one was the AZA group and the other was the non-AZA group. In the AZA group, there were 120 patients, and in the non-AZA group, there were 217 patients. Nine patients of the AZA group were not included, and they were recorded as drop-out patients because they did not complete the follow-up visits. Mean age in the AZA group was 28.41±9.5 years and in the non-AZA group27.27±8.6 years. Mean weight in the AZA group was 53.2±6.5 kg, and in the non-AZA group was 53.01±6.8. Male patients were 13 (3.35%), and female patients were 324 (96.65%). In this study 12 patients TPMT polymorphism and the frequency was 3.56%. Among the 12 polymorphism patients a had TPMT3C mutant allele. There was no TPMT3A and TPMT2 mutant alleles found this study population. Total 10 patients developed myelosuppression. Among them (60%) had TPMT polymorphism and 4 (40%) had no TPMT polymorphism. In AZA group 7 patients had TPMT polymorphism, 6 (85.7%) patients developed myelosuppression and 1 (14.3%) patient did not develop it (myelosuppression). In AZA group was 53.2±6.5 kg and in non-AZA group was 53.01±6.3. Male patients were 13 (3.35%) and female patients were 324 (96.65%). In this study 12 patients TPMT polymorphism and the frequency was 3.56%. Among the 12 polymorphism patients all had TPMT3C mutant allele. There was no TPMT3A and TPMT2 mutant alleles found in this study population. Total 10 patients developed myelosuppression. Among them 6 (60%) had TPMT polymorphism and 4 (40%) had no TPMT polymorphism. In AZA group 7 patients had TPMT polymorphism, 6 (85.7%) patients developed myelosuppression and I (14.3%) patient did not develop it (myelosuppression). In myelosuppressed patients all of them developed anaemia and leucopoenia. Seven of the 10 patients developed thrombocytopenia and pancytopenia. A total of 16 (14.44%) patients developed AZA-induced adverse effects (including myelosuppression). Two patients developed hepatotoxicity who had TPMT genetic polymorphism, but the rest of the nonhematological adverse effects developed in patients without the genetic polymorphism. Conclusion: The frequency of TPMT polymorphism in this series of Bangladeshi SLE patients is 3.56%. Most of the patients with TPMT gene polymorphism developed AZA-induced myelosuppression. The hematological adverse effects of AZA were present both in patients with and without the genetic polymorphism

Conditions

Genetic Polymorphism

Keywords

Azathioprine ,TPMT, Systemic lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• Adverse effect of azathioprine in SLE

  SLADAI Score in SLE

  4 weekly for 12 week

Study Arms (1)

TPMT

TPMT positive in Azathioprine treated adverse effect positive

Drug: Azathioprine (AZA); Drug: TPMT

Interventions

Azathioprine (AZA) DRUG

Patient fulfilled indication of AZA Maintenance of remission of lupus nephritis, Neuro-psychiatric lupus, vasculitis, intolerance to steroid, associate with Defuse Parenchymal Lung Disease (DPLD) Starting AZA at a dose of 1 mg/kg/ body weight First follow-up at 2nd week and change dose of AZA 2 mg /kg/ BW/day Then Follow-up 4 weekly for total 12 week Not adverse effect of Azathioprine

Also known as: Adverse effect of Azathioprine in SLE

TPMT

TPMT DRUG

Adverse effect of azathioprine in SLE

TPMT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

A total of 330 people were included in this study. The study population was SLE patients attending lupus clinics and inpatient clinics. A Convenient sampling procedure was used

You may qualify if:

• Who fulfilled the updated 1997 revised ACR criteria of SLE were included in this study

You may not qualify if:

• The patient was unwilling to participate Had received a recent blood transfusion Had been administered any other myelosuppression drug Had received treatment interfering with the metabolism of AZA or 6 MP, like allopurinol or diuretics Concomitant treatment with cyclosporine, Mycophenolate Mofetil, and pregnancy were excluded from the study

Sponsors & Collaborators

• Bangladesh Medical University: lead

Study Sites (1)

Mohammad Abul Kalam Azad

Dhaka, 1212, Bangladesh

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Azathioprine

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Mohammad AK Azad

  Associate professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 31, 2025
• First Posted: June 10, 2025
• Study Start: January 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2018
• Last Updated: June 10, 2025

Record last verified: 2025-05

Locations

BA (1)