Efficacy And Safety Of Tofacitinib With/without Iguratimod In Rheumatoid Arthritis

Objective:This study aims to explore the efficacy and safety of tofacitinib(TF)combined with/without iguratimod(IGU)in rheumatoid arthritis(RA)patients,and to explore the influence factors of drug response.Methods:In this study,patients with rheumatoid arthritis who attended the outpatient department of the Rheumatology Department in Qilu Hospital of Shandong University from March 2020 to May 2022 were collected.All enrolled patients were treated with TF and IGU(TF+IGU group)or TF(TF group).Follow-up was conducted from the baseline to 48 weeks regularly.Baseline clinical characteristics,previous medication,disease activity and joint function assessment and specific treatment plan were recorded at each follow up timepoint,that is baseline-6-18-30-48 week.Then we compared the disease activity levels between TF group and TF+IGU group,such as Disease Activity Score in 28 joints(DAS28)and Simplified Disease Activity Index(SDAI).We will compare the ACR 20/50/70 response rate,Boolean response rate,EULAR response rate,CliDR response rates,and the occurrence of adverse events(AE)between TF group and TF+IGU group.Baseline DAS28ESR>3.2 was defined as HDA+MDA group,and baseline DAS28ESR≤3.2 was defined as the LDA+REM group.Subgroup analysis and regression analysis were performed to help find factors influencing differences in drug response.Results:1.A total of 100 patients were enrolled and 75 patients completed follow-up.Baseline erythrocyte sedimentation rate(ESR)and DAS28ESR levels were higher in the TF+IGU group than in the TF group.Prior nonsteroidal anti-inflammatory drugs(NSAIDS)usage rate was significantly lower in the TF+IGU group.The TF+IGU group was also significantly lower in the concomitant rate of NSAIDS and methotrexate(MTX)at enrollment.2.Among patients who completed the 48-week follow-up,DAS28ESR and DAS28CRP were decreased in both TF+IGU and TF groups,and disease activity was significantly lower than baseline at 6,18,30,and 48 weeks.DAS28ESR at 18,30 and 48 weeks in TF+IGU group was significantly lower than that at 6 weeks,and DSA28CRP at 30 and 48 weeks was significantly lower than that at 6 weeks(P<0.05).But there was no significant difference in the group comparisons at each follow-up time point.The ACR 20 response rate was higher in the TF+IGU group at 18 weeks than in the TF group(76.8%vs 52.6%,P=0.046).The decrease in ESR and CRP in TF+IGU group was significantly higher than that in TF group,while the decrease in HAQ,T28,SW28,PGA,PHGA and GH-VAS was not significantly different in the two groups.The combined IGU treatment regimen seems to provide a better improvement in inflammatory markers than the improvement in symptoms.Compared with the TF group,the decreases in DAS28ESR and DAS28CRP were more pronounced in the TF+IGU group.3.In the moderate to severe disease activity group(baseline DAS28ESR>3.2,HAD+MDA subgroup),the DAS28ESR and DAS28CRP levels of patients in the TF+IGU group at 30 and 48 weeks were significantly lower than those in the TF group.4.In TF+IGU group,the number of people using sufficient amount of TF and IGU decreased,but no similar trend was found in TF group.In patients treated with glucocorticoids(GC),the disease activity decreased and the GC dose also decreased in TF+IGU group.5.In the subgroup analysis,the level of DAS28ESR decrease in patients with these characteristics was more pronounced in the TF+IGU group,such as female,middle-aged(age≥45 years),long disease duration(>5 years),tender joints of 28 counted(T28)>3 or swollen joints of 28 counted(SW28)>3,health assessment questionnaire(HAQ)≥0.5,and ESR≥18mm/h.Patients with a previous medication history of MTX,hydroxychloroquine(HCQ),leflunomide(LEF),and NSAIDS had a better improvement in DAS28ESR in combination with IGU treatment.6.In the binary logistic regression analysis,T28/SW28>3,HAQ score,ESR≥18mm/h,and DMARDS-IR at baseline were risk factors affecting DAS28ESR remission.After adjusting for age and sex,T28/SW28>3,DMARDS-IR were independent risk factors for DAS28ESR remission,while combined IGU use was an independent protective factor for DAS28ESR remission.7.There was no significant difference in the incidence of adverse events among the two groups,no serious adverse events occurred,indicating the two treatment methods were safe and effective.Conclusion:1.During the 48 weeks of observation,tofacitinib was safe and effective in the treatment of RA.Compared with TF group,the TF+IGU group showed more significant declines in various disease activity indicators.In HDA+MDA group,the disease activity in the TF+IGU group was significantly lower than that in the TF group at the later stage.2.The addition of IGU reduced the GC dose while maintaining decreased disease activity levels,demonstrating that IGU had a synergistic effect.3.Compared with the TF group,the level of DAS28ESR decrease in patients with these characteristics was more pronounced in the TF+IGU group,such as female,middle-aged(age>45 years),long disease duration(>5 years),T28/SW 28>3,HAQ≥0.5,and ESR≥18mm/h.4.T28/SW28>3,DMARDS-IR were independent risk factors for DAS28ESR remission,while combined IGU use was an independent protective factor for patients achieving remission.