| Objective:To explore the influencing factors of difficult-to-treat rheumatoid arthritis(D2T-RA),and provide the basis for risk stratification of patients with rheumatoid arthritis(RA)in the early stage of the disease.Evaluating the efficacy and safety of JAK inhibitors in the treatment of D2T-RA in patients,and provide new ideas for the treatment of D2T-RA.Methods:1.Sixty patients with RA who visited the outpatient and inpatient departments of Department of Rheumatology and Immunology of Lanzhou University Second Hospital from May to July 2021 were selected as the research objects,and they were divided into D2T-RA group(n=23)and RA group(n=37).The clinical data of the two groups were retrospectively analyzed.2.One hundred and twenty-one patients with D2T-RA admitted to the outpatient and inpatient department of rheumatology and immunology in the Second Hospital of Lanzhou University from May 2021 to March 2022 were randomly divided into tofacitinib group(TOF group,n=63)and baritinib group(BARI group,n=58).The dosage was set according to the drug instructions.TOF group was given tofacatib(5mg/tablet)orally,once tablet,twice a day;BARI group was given baritinib(2mg/tablet)orally,once a day,once a day,for 48 weeks.Clinical symptoms,signs,inflammatory indicators,disease activity scores,changes in liver and kidney function and occurrence of adverse reactions were recorded in the two groups before treatment and 4,12,24 and 48 weeks after treatment.Efficacy and safety were compared within and between groups.Measurement data within each group were expressed as mean±standard deviation((?)±s),t test or Mann-Whitney U rank sum test were used.The statistical data were represented by the number of cases(percentage)[n(%)]andχ~2test was used.Among the groups,31 pairs of patients were matched by the propensity score matching method at 1:1,and then the efficacy and safety indicators of these 31pairs of patients before and after treatment were repeatedly measured and analyzed.All data analysised by using SPSS22.0 software.Results:1.Combined osteoporosis,maximum daily dose of oral glucocorticoid,high titers of anti-CCP antibody(OR>1,P<0.05)were independent risk factors for D2T-RA,while initial treatment with methotrexate(OR<1,P<0.05)was protective factor for D2T-RA.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)of anti-CCP antibody for predicting D2T-RA was 0.878,the optimal cut-off value was>92.665RU/ml,and the sensitivity and specificity were82.6%and 86.5%;The AUC for predicting D2T-RA by the maximum daily dose of oral glucocorticoid was 0.889,the optimal cut-off value was>12.5mg/d,and the sensitivity and specificity were 82.6%and 81.1%respectively.2.Compared with before treatment,the number of swollen and painful joints,VAS pain score,inflammatory indicators and disease activity were significantly decreased at 4,12,24 and 48 weeks after tofacitinib treatment,with statistical significance(P<0.05);Compared with 4 weeks of treatment,VAS pain score and disease activity decreased significantly at 12 weeks of treatment,while the number of swollen joints,VAS pain score and disease activity decreased significantly at 24 and48 weeks of treatment,with statistical significance(P<0.05).Compared with before treatment,there were statistically significant differences in the number of white blood cells at 24 and 48 weeks of tofacitinib treatment and the value of aspartate aminotransferase at 24 weeks of tofacitinib treatment(P<0.05).A total of 8 patients stopped medication due to adverse reactions.2.Compared with before treatment,the number of swollen and painful joints,VAS pain score,inflammatory indicators and disease activity were significantly decreased at 4,12,24 and 48 weeks after tofacitinib treatment,with statistical significance(P<0.05);Compared with 4 weeks of treatment,VAS pain score and disease activity decreased significantly at 12 weeks of treatment,while the number of swollen joints,VAS pain score and disease activity decreased significantly at 24 and 48 weeks of treatment,with statistical significance(P<0.05).Compared with before treatment,there were statistically significant differences in the number of white blood cells at 24 and 48 weeks of tofacitinib treatment and the value of aspartate aminotransferase at 24 weeks of tofacitinib treatment(P<0.05).A total of 8 patients stopped medication due to adverse reactions.3.Compared with before treatment,after 4,12,24 and 48 weeks of baritinib treatment,the number of 28 swollen and painful joints,VAS pain score,inflammatory indicators and disease activity were significantly decreased,with statistical significance(P<0.05);Compared with 4 weeks of treatment,VAS pain score and disease activity decreased significantly at 12 weeks of treatment,the difference was statistically significant(P<0.05).The number of 28 painful joints,VAS pain score and disease activity decreased significantly at 24 and 48 weeks of treatment,the difference was statistically significant(P<0.05).Compared with 12 weeks after treatment and 48weeks after treatment,VAS pain score decreased significantly,the difference was statistically significant(P<0.05).Compared with before treatment,there was no statistically significant difference in each safety index after treatment(P>0.05).A total of 5 patients stopped medication due to adverse reactions during medication.4.The comparison between the two matched groups showed that at 12 weeks of treatment,CRP in BARI group was lower than that in TOF group,the difference was statistically significant(P<0.05);at 24 weeks of treatment,CRP and DAS28 scores in BARI group were lower than that in TOF group,the difference was statistically significant(P<0.05);at 48 weeks of treatment,CRP and DAS28 scores in Bari group were lower than that in TOF group,the difference was statistically significant(P<0.05).BARI group had lower VAS pain index,inflammatory index and disease activity than TOF group,the difference was statistically significant(P<0.05),but the total incidence of adverse reactions was not statistically significant(P>0.05).Conclusion:1.Combined osteoporosis,the maximum daily dose of oral glucocorticoid,and Anti-CCP antibody titers are the risk factors for D2T-RA,and methotrexate in the initial treatment is a protective factor.Identifying risk factors and strengthening protective factors has important clinical significance for the occurrence and control of D2T-RA.2.TOF and BARI both showed good efficacy in D2T-RA,and could significantly control disease activity with good safety.3.BARI showed better efficacy and similar safety in improving disease activity over the long term compared to TOF. |
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