乌帕替尼治疗中重度活动性RA的疗效及对血清dsDNA/NETs、MMP-3水平影响的临床研究OA

Objective To Explore the clinical efficacy of Upatinib in the treatment of moderate to severe active rheumatoid arthritis(RA)and its effects on serum levels of free double stranded DNA/neutrophil extracellular traps(dsDNA/NETs)and matrix metalloproteinase-3(MMP-3).Methods 144 patients with moderate to severe active RA admitted to the hospital from August 2022 to August 2025 were selected as the research subjects.The patients were randomly divided into a control group(n=72)and an experimental group(n=72)using a random number table method.The control group was treated with methotrexate combined with leflunomide(The starting dose of methotrexate is 7.5 mg orally per week,increasing by 5 mg every 2 weeks,gradually titrating to 15 mg per week and maintaining.The initial loading dose of leflunomide is 50 mg·d-1,which is taken continuously for 3 days and then converted to the maintenance dose of 20 mg·d-1).The initial loading dose of leflunomide was 50mg·d-1,which was continuously taken for 3 days and then converted to a maintenance dose of 20mg·d-1.The experimental group was treated with combination therapy with Upatinib(15 mg each time,once a day),and both groups completed 12 weeks of continuous treatment.Compare the clinical efficacy,disease activity,serum dsDNA/NETs,MMP-3,and safety between two groups.Results The clinical efficacy of American College of Rheumatology(ACR)20 response,ACR50 response,and ACR70 response in the control group and experimental group after 4 weeks of treatment were 60.00％(42 cases/70 cases)and 71.43％(50 cases/70 cases),25.71％(18 cases/70 cases)and 54.29％(38 cases/70 cases),14.29％(10 cases/70 cases),and 34.29％(24 cases/70 cases),respectively;The clinical efficacy of ACR20 response,ACR50 response,and ACR70 response in the control group and experimental group after 12 weeks of treatment were 82.86％(58 cases/70 cases)and 90.00％(63 cases/70 cases),34.29％(24 cases/70 cases)and 67.14％(47 cases/70 cases),17.14％(12 cases/70 cases)and 48.57％(34 cases/70 cases),respectively.All of the above indicators were better in the experimental group than in the control group(data provided(P＜0.05);After treatment,the levels of helper T cell 17(Th17)in the experimental group and the control group were(3.17±0.48)％and(3.40±0.51)％,respectively,and the levels of regulatory T cells(Treg)were(4.25±0.34)％and(4.10±0.39)％,respectively.The above indicators of the experimental group were significantly different from those of the control group(P＜0.01,P＜0.05).After treatment,the erythrocyte sedimentation rate(ESR)levels of the experimental group and the control group were(25.10±4.89)and(27.99±3.86)mm·h-1,respectively.The C-reactive protein(CRP)levels were(22.46±4.83)and(25.19±5.14)mg·L-1,respectively.The rheumatoid factor(RF)levels were(102.51±20.09)and(114.76±18.37)U·mL-1,respectively.The anti cyclic citrullinated peptide antibody(anti CCP)levels were(46.17±8.91)and(51.79±9.39)RU·mL-1,and the joint disease activity assessment scores(DAS28)were(2.17±0.31),respectively.The above indicators in the experimental group were lower than those in the control group(P＜0.001,P＜0.05),with scores of(2.29±0.39).The serum levels of dsDNA/NETs in the experimental group and the control group were(0.98±0.21)and(1.12±0.15)μ g·L-1,respectively.The levels of MMP-3 were(84.91±10.35)and(91.56±9.18)ng·mL-1,respectively.The above indicators in the experimental group were lower than those in the control group(P＜0.001).After treatment,the levels of alanine aminotransferase(ALT)in the experimental group and the control group were(24.71±6.05)and(24.16±5.71)U·L-1,the levels of aspartate aminotransferase(AST)were(21.87±3.81)and(21.49±4.15)U·L-1,the levels of creatinine(Cr)were(82.49±12.86)and(83.74±15.19)μmol·L-1,and the levels of urea nitrogen(BUN)were(4.54±1.17)and(4.59±1.23)μmol·L-1,respectively.There was no statistically significant difference in the above indicators between the experimental group and the control group(P＞0.05).After treatment,the plasma D-dimer(D-D)levels in the experimental group and the control group were(200.49±20.15)and(214.49±18.60)μg·L-1,respectively.The above indicators in the experimental group were lower than those in the control group,and the difference was statistically significant(P＜0.001).No other safety incidents occurred during the treatment period.Conclusion Upatinib has a good therapeutic effect on moderate to severe active RA,which can effectively improve immune function,reduce CRP,ESR,RF,anti CCP levels,alleviate disease activity,and also have inhibitory effects on dsDNA/NETs and MMP-3.Although there were no safety incidents during the observation period of this study,the long-term safety and protective effect on joint structure still need further verification.