The Association Between Azathioprine Genetic Polymorphisms, Clinical Efficacy and Adverse Drug Reactions Among Egyptian Patients with Autoimmune Diseases

PURPOSE: The study aimed to detect the frequencies of allelic variants (TPMT*3A, TPMT*3C, and TPMT*3G) in the TPMT genes in the Egyptian population and assess the association between TPMT polymorphisms and azathioprine (AZA)—clinical efficacy and adverse drug reactions among Egyptian patients with autoimmune diseases. PATIENTS AND METHODS: DESIGN: A prospective, observational single-center clinical trial. SETTING: Rheumatology and Rehabilitation Department, Kasr Alainy University Hospital, Faculty of Medicine, Cairo University. PATIENTS: Patients attending Kasr Alainy Rheumatology Outpatient Clinic between December 1, 2017 and June 30, 2019 were included in the study after signing a consent form. TPMT genetic polymorphisms were detected for all patients, and the association between polymorphisms presence and azathioprine’s clinical efficacy and adverse drug reactions were determined. RESULTS: A total of 150 patients with a mean age of 35.85 years were enrolled in this study. About 72% of patients were heterozygous in the TPMT*3 G460A and TPMT*3 A719G mutant alleles and 81% were wild type in the TPMT*2 G238C mutant allele. Abnormal liver function tests were detected in 42% of patients. Myelosuppression was presented as anemia which was detected in 63% of patients, leucopenia in 51%, and thrombocytopenia in 25% of patients. AZA clinical failure has occurred in 50% of patients where AZA was discontinued or shifted to another drug which occurred in 45% of patients. Myelosuppression rates were higher in homozygous patients in the three mutant alleles, but statistically significant in TPMT*2 G238C while not statistically significant in TPMT*3 G460A and TPMT*3 A719G. Females had a higher risk of immunosuppression than males (p-value 0.031). CONCLUSION: The study provided an overview of the genomic variations in the Egyptian population. Routine TPMT genotyping prior to the initiation of AZA therapy should be considered.