| Objective: To study the factors and clinical significance of Systemic lupus erythematosus(SLE)on the plasma concentration of hydroxychloroquine(HCQ),and the effect of HCQ plasma concentration on 25(OH)D level,to provide individualized treatment plans for patients with systemic lupus erythematosus to maintain stable conditions.Methods1 Collecting SLE patients who visited the outpatient or inpatient department of the Department of Rheumatology and Immunology of Anhui Provincial Hospital from February 2021 to October 2022 met the inclusion criteria and exclusion criteria,89 patients with SLE who regularly took hydroxychloroquine >for 6 months and had stable condition were the study subjects,and 21 patients with SLE who did not take hydroxychloroquine for the first time were the controls.2 Fill in 《SLE Patient Questionnaire》 and obtain blood samples from SLE patients with the patient’s consent for subsequent determination of HCQ plasma concentration.3 The plasma concentration of HCQ and three metabolites of SLE patients was detected by ultra-performance liquid chromatography mass spectrometer/ mass spectrometer(UPLC-MS/MS),and methodological verification was carried out.4 Serum 25(OH)D level in SLE patients was detected by electrochemiluminescence.5 Statistical analysis was carried out by SPSS software,the influencing factors of plasma concentration of HCQ and metabolites,as well as the influencing factors of 25(OH)D level were analyzed,and the analysis results and clinical significance were discussed.Results1 In this study,a total of 89 patients in the SLE stable group,The plasma concentration of HCQ was 158.10(72.97,284.33)ng/mL,the plasma concentration of desethylhydroxychloroquine(DHCQ)was 87.80(52.39,137.61)ng/mL,and the plasma concentration of desethylchloroquine(DCQ)was 41.46(28.88,81.85)ng/mL The plasma concentration of bisdesethylchloroquine(BDCQ)was 10.86(4.96,19.25)ng/mL.The serum level of 25(OH)D was(21.79±7.06)ng/mL.2 Analysis of plasma concentration of HCQ2.1 The plasma concentration of HCQ in the remission group was 179.19(104.95,292.27)ng/mL significantly higher than that in the low disease activity group HCQ plasma concentration of 105.65(55.78,253.90)ng/ mL level(P<0.05).2.2 HCQ plasma concentration had a significant effect on c-SLEDAI score(P<0.05),ROC curve analysis determined the cut-off value of HCQ plasma concentration,and the cut-off value of HCQ effective plasma concentration was 134.42ng/mL,with a sensitivity of 68.9% and specificity of 59.1%.2.3 The plasma concentration of HCQ was≤134.42ng/mL for 40(44.9%)cases in the low concentration group,and the plasma concentration of HCQ was >134.42ng/mL for49(55.1%)cases in the high concentration group,the BMI,c-SLEDAI,WBC,PLT,C3,C4,DHCQ/HCQ,DCQ/HC/HCQ levels were significantly different between the HCQ low concentration group and the high concentration group(P<0.05).2.4 The plasma concentration of HCQ was positively correlated with PLT(r=0.398,P<0.001),C4(r=0.25,P<0.05),negatively correlated with DHCQ/HCQ,DCQ/HCQ ratios(P<0.05),there was no significant correlation with 25(OH)D,BMI,HCQ daily dose,hormone dose,and C3(P>0.05).3 Analysis of influencing factors of 25(OH)D levels3.1 The level of 25(OH)D(21.79±7.06)ng/mL in the SLE stable group was significantly higher than that in the SLE active group(12.89±7.69)ng/mL(P<0.001).3.2 25(OH)D level was positively correlated with sunshine time,C3,C4,Cr,AST(P<0.05),and negatively correlated with c-SLEDAI(P<0.05).3.3 According to the c-SLEDAI group,the 25(OH)D level of 23.53±7.75 ng/mL in the remission group was significantly higher than that in the low disease activity group of 20.02±5.84 ng/mL(P<0.05).3.4 The critical value of the 25(OH)D level was determined by ROC curve analysis,the optimal diagnostic threshold was 25.5ng/mL,and the sensitivity was 37.8%.,the specificity was 93.2%.3.5 25(OH)D level ≤ 25.5 ng/mL was 69(77.5%)cases in the low-level group,25(OH)D level >25.5 ng/mL was 20(22.5%)cases in the normal level group,there were significant differences between c-SLEDAI,C3,C4 and Cr between the two groups(P<0.05).but there was no obvious difference with plasma HCQ,DHCQ concentration,sunshine time,hormone dose,etc.(P>0.05).4 In the remission group,25(OH)D,C3,C4,ALP were compared with the low disease activity group,the difference was statistically significant(P <0.05).Conclusion1 Monitoring the blood concentration of hydroxychloroquine can help judge medication compliance,improve the rate of SLE remission,reduce disease activity,and increase platelet levels.2 Low 25(OH)D levels in SLE are common,but the shading effect of HCQ does not cause a decrease in blood 25(OH)D levels.3 In Disease activity,SLE should measure blood vitamin D levels,and timely vitamin D supplementation can help reduce disease activity. |
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