Effect of CYP3A4 Gene Polymorphisms on the Clinical Efficacy and Adverse Drug Reactions of Tofacitinib in the Treatment of Rheumatoid Arthritis
Objective To investigate the effect of CYP3A4*4,CYP3A4*18,CYP3A4*1G gene polymorphisms on the clinical efficacy and adverse drug reaction(ADR)of tofacitinib in the treatment of rheumatoid arthritis(RA).Methods A total of 309 RA patients admitted to the Department of Rheumatology and Immunology in the hospital from February 2020 to August 2022 were selected as the RA group,and they were given Citrate Tofacitinib Tablets twice a day for six months with 5 mg each time.In the same period,165 healthy individuals were selected as the control group.Fluorescence polymerase chain reaction(PCR)was used to detect CYP3A4*4,CYP3A4*18,CYP3A4*1G polymorphisms.The clinical efficacy of tofacitinib were evaluated according to the ACR20 criteria issued by the American Society of Rheumatology(ACR),and the RA patients were divided into the improved group(n = 181)and the unimproved group(n = 128)based on whether they met the ACR20 criteria.During treatment,the ADRs related to tofacitinib in RA patients were statistically analyzed.Karch and Lasagna assessment methods were used to determine the causal relationship,RA patients were divided into the ADR group(n = 58)and the non-ADR group(n = 251)based on causal relationship to determine whether it is positive,likely,and possible.Results The differences in CYP3A4*4,CYP3A4*18,and CYP3A4*1G polymorphisms between the RA group and control group were not statistically significant(P>0.05).The difference in RA disease activities between the improved group and the unimproved group was statistically significant(P<0.05),while the difference in CYP3A4*4,CYP3A4*18,and CYP3A4*1G polymorphism between the two groups was not statistically significant(P>0.05).ADRs involved laboratory test abnormalities,skin system,digestive system,respiratory system,and blood system,with twenty-seven cases,eleven cases,seven cases,five cases,and three cases respectively.There were fifty-one mild ADRs and seven moderate ADRs.The difference in CYP3A4*1G polymorphism between the ADR group and the non-ADR group was statistically significant(P<0.05),while the difference in CYP3A4*4 and CYP3A4*18 polymorphism between the two groups was not statistically significant(P>0.05).Conclusion There is a correlation between CYP3A4*1G polymorphism and the ADRs of tofacitinib in the treatment of RA.In the clinical use of tofacitinib,the patient′s CYP3A4*1G gene polymorphism should be monitored,and the dosage should be adjusted if necessary to ensure medication safety.
cytochrome P450 proteinsgene polymorphismtofacitinibrheumatoid arthritisclinical efficacyadverse drug reactions
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维普
